N O V O C A S T R A A N T I B O D I E S , K R E AT E C H P R O B E S , B O N D R E A G E N T S , B O N D S Y S T E M & T H E R M O B R I T E

IHC & ISH
PRODUCT CATALOGCONTENTS
HOW TO USE THIS CATALOG
ADDITIONAL INFORMATION..........................................................................................................................................................3
KEY..................................................................................................................................................................................................3
AUTOMATEDBOND-III..........................................................................................................................................................................................7
BOND-MAX......................................................................................................................................................................................7
BOND RX.........................................................................................................................................................................................9
BOND RXM.......................................................................................................................................................................................9
CEREBRO......................................................................................................................................................................................11
THERMOBRITE.............................................................................................................................................................................13
THERMOBRITE ELITE...................................................................................................................................................................14
COMPANION DIAGNOSTICS
BOND ORACLE HER2 IHC SYSTEM..............................................................................................................................................15
LEICA HER2 FISH SYSTEM..........................................................................................................................................................17
BOND DETECTION
BOND POLYMER REFINE DETECTION.........................................................................................................................................21
BOND POLYMER REFINE RED DETECTION .................................................................................................................................21
CHROMOPLEX 1 DUAL DETECTION............................................................................................................................................22
BOND FISH KIT.............................................................................................................................................................................22
BOND INTENSE R DETECTION ....................................................................................................................................................23
BOND RESEARCH DETECTION ....................................................................................................................................................23
BOND RNASCOPE DETECTION REAGENTS - BROWN.................................................................................................................24
BOND READY-TO-USE ANTIBODIES.............................................................................................................................................25
ADVANCED STAINING – XL FISH PROBES FOR BOND..................................................................................................27
ADVANCED STAINING – BOND CISH PROBES..............................................................................................................32
ADVANCED STAINING – BOND ANCILLARIES..............................................................................................................36
ADVANCED STAINING – BOND CONSUMABLES...........................................................................................................42
ADVANCED STAINING – MANUAL DETECTION - IHC....................................................................................................47
ANTIBODIES..............................................................................................................................................................53
IVD PROBES.............................................................................................................................................................153
RUO PROBES...........................................................................................................................................................229
INDEX......................................................................................................................................................................304

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HOW TO USE
T H I S C ATA L O G
Products in this catalog are listed alphabetically in sections according to their product type. The Primary Antibodies and ISH Probes sections include
products in manual and BOND Ready-to-Use formats. This makes it easy to search for the required antibody and to identify the best available format
for the intended application.
To find a product, either use the contents page to locate the appropriate section and then go directly to the product, or use the product name index
at the back of the catalog.

ADDITIONAL INFORMATION

KEY

Products are listed with their product code and volume/approximate
number of tests. Primary antibody listings include the clone, format,
tissue utility and recommended retrieval.
Regional product availability is defined by three categories, which aredetailed below:
US
United States of America.
EU
Austria, Belgium, Denmark, Finland, France, Germany, Greece,
Ireland, Italy, Malta, Netherlands, Portugal, Spain, Sweden,
Switzerland, United Kingdom.

IVD

In vitro diagnostic use

RUO

For Research Use Only. Not for use in diagnostic
procedures

ASR

Analyte Specific Reagent. Analytical andperformance characteristics are not established

GPR

General Purpose Reagent

F

FrozenP

ParaffinO

Other applications

W

Western blotting

P (HIER)	Paraffin sections with heat induced epitope
retrieval recommended

ROW
All other countries not listed above.

P (ENZYME)	Paraffin sections with enzyme digestion
recommended

For more specific information regarding availability in your region,please consult your Leica Biosystems sales representative.

P (ENZYME+HIER)	Parffin sections with enzyme digestion followed
by heat induced epitope retrieval recommended
P (ENZYME/HIER)	Paraffin sections with enzyme digestion orheat induced epitope retrieval recommended optimum pretreatment to be determined by end
user
The first letters of the product code indicate the product type.

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NCL

Concentrated primary antibody or
miscellaneous products

RTU

Ready-to-Use primary antibody

RE

Manual detection or ancillary reagent

PA

BOND format primary antibody

PB

BOND format ISH probe

AR

BOND ancillary reagent

DS

BOND detection system

KBI

Kreatech IVD productsKI

Kreatech RUO products

AUTOMATED
BOND ECOSYSTEM....................................................................................... 6

BOND EBER PROBE..................................................................................... 33

BOND-III......................................................................................................... 7

BOND CMV PROBE...................................................................................... 33

BOND-MAX..................................................................................................... 7

BOND HPV (SUBTYPES 6, 11) PROBE......................................................... 34

BOND RX........................................................................................................ 9

BOND HPV (SUBTYPES 16, 18, 31, 33, 51) PROBE..................................... 34

BOND RX ...................................................................................................... 9

BOND DNA POSITIVE CONTROL................................................................. 35

CEREBRO..................................................................................................... 11

BOND DNA NEGATIVE CONTROL............................................................... 35

THERMOBRITE............................................................................................ 13

BOND RNA POSITIVE CONTROL PROBE.................................................... 35

M

THERMOBRITE ELITE.................................................................................. 14

BOND RNA NEGATIVE CONTROL PROBE................................................... 35

COMPANION DIAGNOSTICS...............................................................15

BOND ANCILLARIES...........................................................................36

BOND ORACLE HER2 IHC SYSTEM............................................................. 15

BOND DEWAX SOLUTION............................................................................ 36

LEICA HER2 FISH SYSTEM......................................................................... 17

BOND WASH SOLUTION 10X CONCENTRATE............................................ 36

BOND DETECTION..............................................................................21

BOND EPITOPE RETRIEVAL SOLUTION 1................................................... 37

BOND POLYMER REFINE DETECTION........................................................ 21

BOND EPITOPE RETRIEVAL SOLUTION 2................................................... 37

BOND POLYMER REFINE RED DETECTION ................................................ 21

BOND UNIVERSAL COVERTILE................................................................... 38

CHROMOPLEX 1 DUAL DETECTION........................................................... 22

BOND PRIMARY ANTIBODY DILUENT......................................................... 38

BOND FISH KIT............................................................................................ 22

BOND ENZYME PRETREATMENT KIT......................................................... 39

BOND DETECTION....................................................................................... 22

BOND DAB ENHANCER............................................................................... 39

BOND INTENSE R DETECTION ................................................................... 23

BOND ANTI-FLUORESCEIN ANTIBODY....................................................... 40

BOND RESEARCH DETECTION ................................................................... 23

BOND HYBRIDIZATION SOLUTION............................................................. 40

BOND DETECTION....................................................................................... 23

BOND ANTI-BIOTIN ANTIBODY................................................................... 40

BOND RNASCOPE DETECTION REAGENTS - BROWN................................ 24

BOND STRINGENCY WASH......................................................................... 41

BOND DETECTION....................................................................................... 24

BOND RNASCOPE PROTEASE.................................................................... 41

BOND READY-TO-USE ANTIBODIES....................................................25

BOND CONSUMABLES.......................................................................42

XL FISH PROBES FOR BOND...............................................................27

BOND ASPIRATING PROBE CLEANING SYSTEM....................................... 42

2P23 ALK (2P23) BREAK57........................................................................ 27

BOND MIXING STATIONS............................................................................ 42

6Q22 ROS1 (6Q22) BREAK57...................................................................... 27

BOND OPEN CONTAINERS 7 ML................................................................. 42

7Q31 MET (7Q31) / SE7 (D7Z1)57.............................................................. 28

BOND OPEN CONTAINERS 30 ML.............................................................. 42

8P11 FGFR1 (8P11) / SE8 (D8Z1)57........................................................... 28

BOND TITRATION KIT.................................................................................. 43

10Q11 RET (10Q11) BREAK57.................................................................... 29

BOND TITRATION CONTAINER INSERTS.................................................... 43

8Q24 MYC (8Q24) BREAK57....................................................................... 29

BOND SLIDE LABEL AND PRINT RIBBON KIT............................................. 43

14Q32 IGH (14Q32) BREAK57.................................................................... 30

BOND REAGENT TRAY................................................................................. 43

18Q21 BCL2 (18Q21) BREAK57.................................................................. 30

BOND SLIDE TRAY....................................................................................... 44

3Q27 BCL6 (3Q27) BREAK57...................................................................... 31

BOND SYRINGE (FOR 9-PORT PUMP)......................................................... 44

17P13 TP53 (17P13) / SE 1757.................................................................. 31

BOND PLUS SLIDES..................................................................................... 45

BOND CISH PROBES...........................................................................32

BOND COVERTILE CLEANING RACK.......................................................... 45

BOND KAPPA PROBE.................................................................................. 32
BOND LAMBDA PROBE............................................................................... 32

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BOND ECOSYSTEM
A complete IHC and ISH solution that delivers optimal results
BOND DETECTIONSYSTEMS• BOND Polymer Refine Detection (Brown)• BOND Polymer Refine Red Detection• ChromoPlex 1 Dual Detection for BOND

BOND READY‑TO‑USE
ANTIBODIESUSING TRUSTEDNOVOCASTRA CLONES
Comprehensive range of ready-to-use antibodies
spanning across 14 pathology menus.

NOVOCASTRA HD
ANTIBODIESThe BOND RTU range includes Novocastra
HD antibodies that have been independently
validated by NordiQC for optimal performance.
NOVOCASTRA HD BOND RTU CD10 (56CD6)

ROCHE TISSUE DIAGNOSTICS

BOND ANCILLARIES AND CONSUMABLES

Ready-to-use solutions designed to be used on the BOND system

BOND Universal Covertile facilitates gentle, even reagent flow over tissue* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

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F U L LY A U T O M AT E D, C L I N I C A L ,I H C & I S H S TA I N E R S

BOND-IIIFor high throughput labs who require
exceptional slide TAT (turnaround time),
coupled with high quality staining.

2.5 HOURSLIDE TAT

Finish earlier. BOND-III consistently
completes IHC slides in 2.5 hours
whether your workflow is batch orcontinuous.

BOND-MAX
With a case throughput superior tolarger instruments, BOND-MAX is ideal
for space-constrained laboratories.

SMALL
FOOTPRINT
Meet the demands of ever-increasing slidevolumes with the space you have.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

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F U L LY A U T O M AT E D, C L I N I C A L ,I H C & I S H S TA I N E R S

BOND RTU

OPTIMAL STAINING

Optimized and validated for use on BOND systems.

The BOND platform used in conjunction with Novocastra HD Antibodies and
BOND detection systems is a fully integrated solution delivering optimal
staining outcomes.

High quality results in three easy steps:

LEICA BIOSYSTEMS

1. LOAD

2. SELECT

3. RUN70%

Eliminate mixing, titration and dilution.

Novocastra HD Antibodies
classified as optimal staining*

ROCHE TISSUE DIAGNOSTICS

vs33%
Roche Antibodies classified
as optimal staining** Based on a comparison of 67 equivalent RTU antibodies

DESIGNED WITH
THE USER IN MINDINTERCONNECTIVITY
SUITE

BOND Platform software features an intuitive user interface incorporating
highly visual modular iconography which is easy to use and learn.

With BOND in your lab, you can connect with tools designed to make yourlife easier. Turn your lab into a paragon of efficiency and reap the results.
• CEREBRO Specimen Tracking and Workflow Management• BOND LIS-ip, bidirectional LIS interface• BOND-ADVANCE Network, deploy up to 30 instruments on a single
unified network* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

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F U L LY A U T O M AT E D,
R E S E A R C H S TA I N E R S

BOND RXFor research labs and academical centres
who want to accelerate their test program.

BOND RXm
For labs with limited space whowant to explore their ideas.

FOR RESEARCH USE ONLY. NOT FOR USE IN DIAGNOSTIC PROCEDURES.
* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

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A WHOLE SUITE OF OPEN INNOVATIONPARTNERS TO CHOOSE FROMFREEDOM TO DISCOVERE X P LO R E YO U R I D E A SIFIMMUNOFLUORESCENCETSA

TYRAMIDE SIGNALAMPLIFICATIONCISH

CHROMOGENIC IN SITUHYBRIDIZATIONCTC

CIRCULATING TUMOUR
CELLS

FISH

FLUORESCENCE IN SITUHYBRIDIZATIONTUNELTERMINAL DEOXYNUCLEOTIDYL
TRANSFERASE DUTP NICK END
LABELING ASSAY

A C C E L E R AT E Y O U RTEST PROGRAMCOMMERCIALIZE
YOUR DISCOVERY

bDNA

BRANCHED DNA ASSAYS

LNA

LOCKED NUCELIC ACID

miRNA

Customize your protocols

MICRORNA

Complete your test program sooner
with speed, consistency and efficiency

A path from research to the clinic

OPEN INNOVATION PARTNERS

Choose from an expanding range of innovation partners bringing new technologies to the research lab, automated for use on BOND RX and BOND RXm

ACD

AKOYA

Fully integrated RNA ISH solution

Walk away multiplexing

ULTIVUERARECYTE

Single step multiplexing

CTC analysis from whole blood
FOR RESEARCH USE ONLY. NOT FOR USE IN DIAGNOSTIC PROCEDURES.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

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SPECIMEN TRACKING ANDW O R K F LO W M A N AG E M E NTCEREBROGo home at the end of each day confident thatevery patient specimen will reach the pathologist
for diagnosis as quickly as possible.

A DOCUMENTED CHAIN OF CUSTODY FOR ALL
ANATOMIC PATHOLOGY AND CYTOLOGY SPECIMENSACCESSIONINGGROSSINGACCESSIONING

CENTRIFUGINGTISSUE PROCESSINGHISTOLOGYCYTOLOGY* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.

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EMBEDDING

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DON’T LET IDENTIFICATION ERRORS LEAD
TO PATIENT HARMPAT I E N T S A F E T Y
ID Confirmed. All specimens accounted for. Every taskcomplete. Track and verify each item and case throughevery AP workflow step in your lab.

PRODUCTIVITY
Save thousands of hours a year on non-value adding tasks.
Eliminate handwriting. Reduce repetitive data entry.
Real-time information to make data driven decisions.

SUPERIOR FLEXIBILITY
Don‘t Compromise. Give your lab a competitive advantage.
Integrate with your preferred instruments and IT systems.
Coverage across a variety of workflow types.

SECTIONING

STAINING

SEND-OUTREPORTING

UNIVERSAL

Additional fixation
Decalcification
Frozen section
Specimen storage
Slide archival
Block archival
Tracking referred cases
Delivery to pathologist
Pathologist review
Queued work

SMEARING* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.

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THERMOBRITE
Automates the denaturation and hybridization steps in slide-based FISH procedures,and provides walk-away convenience for clinical and research personnel. The low cost
unit accepts a wide range of sample types, is easy to use, and reduces hands-on timeby more than 50% while ensuring overall precision and accuracy in FISH assays.

USER PROGRAMMABLE
SETTINGS• 40 user defined protocols and3 operating modes• Easy to read backlit display• Numeric keypad allows foreasy programming• Fixed temperature setting forslide baking

EASY TO USE• Reduces hands-on time during
ISH procedures• Does not need to be fully loaded tomaintain temperature accuracy• Slide separator keeps slides in place andallows for one hand removal

PRODUCT DESCRIPTIONPRODUCT CODE

ThermoBrite Slide Denaturation/Hybridization System 120V

3800-004852-001

ThermoBrite Slide Denaturation/Hybridization System 240V

3800-004852-002

Humidity Card, 10pk

3800-004970-001

ThermoBrite Temperature Verification Kit

3800-006418-001

A D VA N TA G E SOVER MANUALPROCESSING• Replaces water bath and hybridizationoven• Superior temperature control compared towater bath
• No need to denature slides intoxic formamide• No need to denature probes separately• Eliminates many manual steps* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

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THERMOBRITE ELITE
Automates and standardizes the FISH slide preparation process including deparaffinization,
pretreatment, denaturation/hybridization and post hybridization wash. Application of probe,
counterstain and cover slipping are the only manual steps. Just load your slides and walk away.

Minimal hands-on time frees up technologists for other important tasks. The ThermoBrite Elite hybridizes with temperature controlled to +/- 1°C and canprocess up to twelve slides per run with the ability to adapt to smaller batches. For higher throughput, transfer slides to a standard ThermoBrite instrument
to denature/hybridize and continue using your ThermoBrite Elite for new runs. The included intuitive software enables users to run preload protocols for solid
tumor/FFPE, urine, or to create up to 1,000 user defined protocols. The instrument can be programmed to work with nearly any probe or protocol, allowing theselection of up to ten input reagents and three separate waste paths.

F E AT U R E SSPEED &EFFICIENCYFLEXIBILITY• Small bench top unit
• Automated fluidic system• Hybridization temperature precision
to +/- 1°C• Workflow based software navigation• Open system—preloaded &custom protocols• Fast protocol setup and start of run• Hands on time reduced to 3 steps from>30 (FFPE)• Free up technologists for other tasks• Flexible and easy-to-use• Increases laboratory productivity

PRODUCT DESCRIPTIONPRODUCT CODEPRODUCT DESCRIPTION

ThemoBrite Elite 120V

3800-007000-001

ThemoBrite Elite 240 V

Histology (solid tumor/FFPE specimens)
Cytology (urine and other fluids)
Hematology (blood/bone marrow)
Cytogenetics (metaphase/interphase,tissue)PRODUCT DESCRIPTIONPRODUCT CODE

TBE Wash buffer (250 mL 10x) LK-141B

20 x SSC

LKU-061A

3800-007000-001

20 x SSC

LK-061A

Pretreatment Solution B

LKU-100C

Peritubes 2 tubes

3800-010022-001

Pretreatment Solution B

LK-100C

Pretreatment Solution A

LKU-110C

Peritubes 12 tubes

3801-010021-001

Pretreatment Solution A

LK-110C

Wash Buffer V (10x)

LKU-141B

Wash Buffer V (10x)LK-141B

Wash Buffer V (10x)

LKU-141C

Wash Buffer V (10x)LK-141C

Pretreatment Solution A (1 L) LK-110C

PRODUCT CODE

•
•
•
•

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

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COMPANION DIAGNOSTICS
BOND ORACLE HER2 IHC SYSTEM
WITH TREATMENT DECISIONS DEPENDENT ON A STAINED SLIDE, YOU NEED CONFIDENCE THAT YOUR HER2 IHCSTAINING IS CONSISTENT AND ACCURATE.
The BOND Oracle HER2 IHC system gives you the confidence that comes with demonstrated HER2 IHC FISH concordance andcomplete assay validation. With the Oracle system, you get the accurate results needed for effective patient management.

PRODUCT CODE:

CLONE:

NO. OF TESTS:KIT CONTENTS:

TA9145CB11

60 tests (150 slides)

HER2 Control Slides (x15)
HER2 Primary Antibody
HER2 Negative Control
Integrated DAB Detection System* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

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COMPANION DIAGNOSTICS

MAXIMIZE EFFICIENCY
A complete solution of Ready-to-Use reagents,
HER2 Control Slides, BOND automation anda validated, standardized protocol reduce thepotential for repeat testing and free skilled staff
for other high-value tasks.

0

DRIVE CONSISTENCY
A validated, standardized protocol for uniform
staining consistency is supported by conveniente-learning which reinforces and tests consistentinterpretation of Oracle HER2 IHC staining.

1+

2+

HER2 CONTROL SLIDESINCREASE CONFIDENCE
Confidence in HER2 testing is enhanced by HER2
control slides demonstrating 0, 1+ , 2+ and 3+
staining, and excellent FISH concordance.

3+

BREAST TISSUEG A S T R I C T I S S U E **** This product is not for use in gastric cancer in the USA.
* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

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COMPANION DIAGNOSTICS
LEICA HER2 FISH SYSTEMFULLY AUTOMATED LEICA HER2 FISH SYSTEM FOR BOND
Contains PathVysion®** FISH Probes supplied by Abbott Molecular Inc.

PRODUCT CODE:

CLONE:

NO. OF TESTS:KIT CONTENTS:

TA9217-30 tests (30 slides)

RTU LSI HER2/CEP17 dual probe
Post Hybridization Wash Solution 2
BOND Enzyme Diluent
BOND Enzyme Concentrate 2
BOND Open Containers** PathVysion LSI and CEP is a trademark of Abbott Molecular Inc. All Rights Reserved. Used under License. This product is not for sale in the USA.
* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

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COMPANION DIAGNOSTICSEASYEFFICIENT

Eliminate complexity and reduce human errorsthat may compromise patient care.
With fully automated staining, laboratories willfind it easy to produce the consistent, highquality stained slides that pathologists rely on.
SUPERIOR QUALITY & STANDARDIZATIONThe Leica HER2 FISH System is a complete andfully compatible diagnostic kit, containing all thecomponents required to run the entire test on the
BOND System.
REDUCED ERRORS & LOWER REPEAT RATESLeica Biosystems recommended BOND protocols
provide uniform staining consistency. Precise
BOND automation ensures reduced process
variation to dramatically reduce the number of
repeats and save valuable hands-on time.

A C C U R AT E

Work smarter, increase efficiency and provide
an improved service to your clinicians
and customers. BOND automation brings
optimized workflow to HER2 FISH staining.
With automation, an optimized protocol andstandardized Ready-to-Use reagents, the HER2FISH System provides the flexibility, reduced
hands-on time and reduced turnaround time thattoday’s Lean workflow demands.

The Leica HER2 FISH System provides a
Total Solution. The system combines Abbott
Molecular Inc’s HER2 FISH probes with the BOND
automated platform. The reduction in variationdelivers a high level of diagnostic confidence
when combined with proprietary HER2 FISH
Control Slides.

FULLY AUTOMATED & FLEXIBLE

The easy-to-read, single slide, dual probe
fluorescent staining provides the highest quality
result for the assessment of HER2 gene status.

Three independent slide trays mean the BOND
System keeps your cases organized whileproviding the flexibility for optimal workflow
scheduling of your IHC and ISH tests.
MAXIMIZE EFFICIENCY & MINIMIZE COSTS
Free your skilled staff for other high-value tasks
by automating labor intensive FISH techniques.
The Leica HER2 FISH System brings time,
workflow and ultimately cost efficiencies to yourlaboratory.

QUICKLY DELIVER ACCURATE RESULTSDIAGNOSTIC CONFIDENCE
Now you can be confident you have done
everything to deliver the accurate results neededfor effective patient care.

** PathVysion LSI and CEP is a trademark of Abbott Molecular Inc. All Rights Reserved. Used under License. This product is not for sale in the USA.
* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

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COMPANION DIAGNOSTICS
CUTTING EDGE COLLABORATIONPARTNER WITH THE LEICA BIOSYSTEMS COMPANION DIAGNOSTICS (CDX)
TEAM FOR YOUR NEXT DIAGNOSTIC DEVELOPMENT PROJECT.
Our CDx team collaborates with leading biotechnology and pharmaceutical companies. Together, wedevelop and commercialize cutting-edge diagnostic test solutions that help identify patients who are likely
to benefit from our partners’ emerging therapies, a critical element of personalized medicine.

We are uniquely positioned to drive personalized healthcare by ensuring patients receive a timely and accurate diagnosis,
a critical part of VISION24, our vision statement. Partnering with Leica Biosystems for your CDx needs provides:

DEDICATED AND
EXPERIENCED
CDX TEAMFLEXIBLE
DEVELOPMENTAND
PARTNERSHIP
MODELS

TRANSPARENTPARTNERSHIPSGLOBAL
NETWORKSAND STRATEGICPARTNERSHIPSUNIQUELYPOSITIONEDTO ADDRESSFUTURE CDX
UNMET NEEDS* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

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COMPANION DIAGNOSTICS
A DEDICATED TEAMOUR STRATEGIES ARE FLEXIBLE AND RESPONSIVE TO THE PHARMAPARTNER’S DEVELOPMENT SCHEDULE AND OBJECTIVES.
Each CDx project is assigned to a cross-functional team that works closely with our Pharma
Partners throughout the IVD development process. The cross functional teams support:

ASSAY DEVELOPMENT

Our dedicated and experienced
CDx team leverages our flexible
development and partnershipmodels to function withtransparency and economic
consciousness for our
Pharma Partners’ needs.
Assay development is carried out
under Design Control standards.
A standardized process also
allows for consistent output androbust diagnostic products.

CLINICAL AFFAIRSREGULATORY AFFAIRSCOMMERCIALIZATIONOur clinical affairs team’s
relevant IVD industry expertise
across Asia, Europe, and theAmericas ensures successful
coordination and execution of
global clinical programs.

This team includes professionals
with deep experience in CDx
development, using an establishedregulatory infrastructurethat lets us support Pharma
Partners worldwide.

CDx products are launchedusing Danaher Business System(DBS) tools, which provide leanand commercial support tonumerous companies acrossa variety of industries.

We have the flexibility to work with
contract research organizations(CROs) and trial sites selectedby our Pharma Partners.

We take a global lifecycle
approach to regulatory
planning and execution, withextensive experience in drug
and device submissions incountries across the world.

Our team of Market Accessprofessionals has expertise in:health policy, payer relations(Government and Private), clinicaloutcomes and health economic
evidence, which are needed
to meet HTA requirements.

WE SUPPORT THE CURRENT AND FUTURE CDX UNMET NEEDS INCLUDING:DIGITAL PATHOLOGY SOLUTIONS, MULTI-MODAL TECHNOLOGY, AND
MULTIPLEXING USING OUR IHC, ISH, AND RNA ISH SOLUTIONS.

Marker 1(Brown) and Marker 2(Red) IHC

Marker 3(RNAscope-BROWN) + Marker1/Marker2 (IHC Cocktail-RED)* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

20

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V

A

N

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E

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S

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A

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BOND Polymer Refine Detection
FORMAT
200-300 Tests

CODE
DS9800

USAGE
-

–

B

O

N

D

D

E

T

E

C

T

I

O

N

BOND Polymer Refine Red Detection
STATUSFORMAT
100 Tests

IVD

CODE
DS9390USAGE-

STATUSIVDAPPLICATIONAPPLICATION

Immunohistochemistry (IHC)

Immunohistochemistry (IHC)

Primary antibody binding to tissue sections can be visualized using BOND
Polymer Refine Detection, where it provides intense, high resolution staining.
A range of BOND Ready-to-Use primary antibodies are available,or alternatively, use antibody concentrates diluted with BOND Primary
Antibody Diluent (AR9352).

Primary antibody binding to tissue sections can be visualized using the BOND
Polymer Refine Red Detection, providing an intense and high resolution stain.
COMPONENTS
BOND Polymer Refine Red Detection is an IVD labeled red detection system
for the automated BOND system. BOND Polymer Refine Red Detection isbiotin-free, utilizing alkaline phosphatase (AP)-linked compact polymer toprovide enhanced tissue penetration and unsurpassed reagent sensitivity. It
contains post primary, polymer reagent, Fast Red chromogen, and hematoxylin
counterstain and is supplied in a convenient, Ready-to-Use format.

Chromogenic in situ Hybridization (ISH)
BOND Polymer Refine Detection produces highly specific, sensitive andreproducible demonstration of nucleic acid sequences through controlled
hybridization reactions.
COMPONENTS
A state-of-the-art Compact Polymer detection system HRP horseradish
peroxidase (HRP) polymer for use in both immunohistochemistry andchromogenic in situ hybridization. Small multifunctional linkers enhance tissue
penetration, producing unsurpassed sensitivity. The system is biotin-free.
BOND Polymer Refine Detection contains a peroxide block, post primary,polymer reagent, DAB chromogen and hematoxylin counterstain. It is supplied
ready-to-use for the automated BOND system.

Human skin stained for melanoma marker HMB45 using BOND Polymer Refine Red
Detection. Note intense cytoplasmic staining of melanocytes in contrast to the brown
endogenous melanin.

Colon mucosa: immunohistochemical staining with BOND Ready-to-Use Cytokeratin 8/18
(5D3) (PA0067) using BOND Polymer Refine Detection.

BOND Polymer Refine Red Detection.

BOND Polymer Refine Detection.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

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ChromoPlex 1 Dual Detection
FORMAT

CODE

USAGE

–

B

O

N

D

D

E

T

E

C

T

I

O

BOND FISH Kit
STATUSFORMAT

CODE

USAGE

STATUS

50 Tests

DS9665-IVD

60 TestsDS9636-

IVD

100 Tests

DS9477-

IVD

60 Tests

DS9374-GPR

APPLICATIONAPPLICATION

Immunohistochemistry (IHC)

Fluorescent in situ Hybridization (FISH)

When tissue is limited and a diagnosis is required, the most effective useof tissue sections becomes imperative. With ChromoPlex 1 Dual Detection
for BOND, you can view multiple antibodies using two distinctive chromogens
on a single slide, to give you a faster, more comprehensive result for clinicalassessment.

The BOND FISH Kit enables the user to perform fluorescence in situ
hybridization (FISH) on the automated BOND system. It is intended foruse with nucleic acid probes on formalin-fixed, paraffin embedded (FFPE)
tissue. The kit consists of a formamide mixture which reduces non-specifichybridization of nucleic acid probes.

COMPONENTS

RESTRICTIONS

ChromoPlex 1 Dual Detection is a biotin-free, polymeric horseradish
peroxidase (HRP)-linker and polymeric alkaline phosphatase (AP)-linker
antibody conjugate system for the detection of tissue-bound mouse and rabbit
IgG primary antibodies. It is intended for parallel staining sections of formalinfixed, paraffin-embedded tissue on the BOND automated system.

DS9636 is not available for sale in the US.
DS9374 is only available in the US.

BOND FISH Kit.
Sensitive and specific staining of the basal cell layer of a prostate biopsy with DAB
chromogen. Excellent staining intensity of malignant cells detected with Fast Red
chromogen. Prostate Biopsy stained with ChromoPlex 1 Dual Detection and a prostate
cocktail (PIN-4).

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

22

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V

A

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BOND Intense R Detection
FORMAT
200 Tests

CODE
DS9263

B

O

N

D

D

E

T

E

C

T

I

O

BOND Research Detection
USAGE

-

–

STATUSFORMAT

RUO

CODE

USAGE

STATUS

200 Tests

DS9455-RUO

200 Tests

DS9777-RUO

APPLICATIONAPPLICATION

Immunohistochemistry (IHC)

BOND Research Detection offers researchers the ability to tailor applications
and fully automate staining for ease of use.

By allowing a free choice of biotinylated secondary antibody, BOND Intense
R Detection is ideal for the detection of primary antibodies from any
species. Research applications such as IHC staining of mouse tissues canbe accommodated in this manner. The intense deposition of DAB reaction
product produces strong immunostaining.

COMPONENTS
BOND Research Detection System (DS9455), this open detection system
consists of six standard 30 mL open containers in a reagent tray.

COMPONENTS

BOND Research Detection System 2 (DS9777), this open detection system
consists of nine standard 30 mL open containers in a reagent tray.

BOND Intense R Detection is a peroxidase detection system optimized foruse on the automated BOND system and is ideal for research applications. It
contains a peroxide block, streptavidin/peroxidase conjugate, DAB chromogen
and hematoxylin counterstain. Users must supply a biotinylated secondary
antibody of their choice.

BOND Research Detection.

BOND Intense R Detection.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

23

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–

B

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D

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C

BOND RNAscope Detection Reagents BROWNFORMAT
60 Tests

CODE
DS9790USAGE-

STATUSGPRAPPLICATIONThe BOND RNAscope Detection Reagents - BROWN consists of a series ofreagents that enable visualization of RNA in FFPE (formalin fixed, paraffinembedded) tissue following hybridization with a target RNA specificoligonucleotide probe. The sequential addition of the reagents after probehybridization results in RNA target and signal amplification, visualized throughchromogenic conversion of DAB by HRP. The detection reagents enablechromogenic RNA ISH to be performed on the automated BOND-III system.
COMPONENTS
BOND RNAscope Detection Reagents – BROWN is ready to use.
Reconstitution, mixing, dilution or titration of this reagent is not required.
This product contains:
•
•
•
•
•
•
•
•
•
•
•
•

RNAscope Rinse
Hematoxylin
DAB Part 1
DAB Part B
RNAscope Bluing
RNAscope AMP 1 DAB
RNAscope AMP 2 DAB
RNAscope AMP 3 DAB
RNAscope AMP 4 DAB
RNAscope AMP 5 DAB
RNAscope AMP 6 DAB
RNAscope H2O2BOND RNAscope

BOND RNAscope Detection Reagents - BROWN* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

24

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A D V A N C E D

S T A I N I N G–

B O N DB O N DR E A D Y - T O - U S E

A N T I B O D I E S

RT U S

ENHANCE LABORATORY PRODUCTIVITY
NAME

CLONE

7 ML

30 ML

NAME

CLONE

7 ML

30 ML

ALK

5A4

PA0306

-

CD43

MT1

PA0938

-

ALK

5A4

PA0831-CD45

X16/99PA0042-Alpha Fetoprotein

C3

PA0963-

CD45RO

UCHL1

PA0146

-

CD5

4C7

PA0168-

CD56 (NCAM)

CD564

PA0191-

Alpha-Methylacyl-CoA Racemase(AMACR, p504s)

EPMU1

PA0210-B Cell Specific Octamer Binding Protein-1(BOB-1)

TG14

PA0558

-

CD57

NK-1

PA0443-

Bcl-2 Oncoprotein

bcl-2/100/D5

PA0117-

CD61 (GPIIIa)

2f2

PA0308-

Bcl-6 Oncoprotein

LN22

PA0204-

CD68

514H12

PA0273-

Beta-Catenin

17C2

PA0083

-

CD7

LP15

PA0266-

CA125 (Ovarian Cancer Antigen)

Ov185:1

PA0539

-

CD79a

11E3

PA0192-

CA19-9 (Sialyl Lewisa)

C241:5:1:4

PA0424-

CD79a

JCB117

PA0599-Calcitonin

Polyclonal

PA0406

-

CD8

4B11

PA0183-

Calponin (Basic)

26A11

PA0416

-

CDX2

EP25

PA0375-

Calretinin

CAL6

PA0346-c-erbB-2 Oncoprotein (HER-2) Antibodies

CB11

PA0983

Carcinoembryonic Antigen (CD66e)

COL-1

PA0848-

PA0571(13.5 mL)

CD10

56C6

PA0270

PA0131Chromogranin A

5H7

PA0515

-

CD103

EP206

PA0374-Cyclin D1

EP12PA0046

-

CD117

EP10

PA0007-

Cytokeratin (8/18)

5D3PA0067

-

CD11c

5D11

PA0554-

Cytokeratin 14

LL002

PA0074

-

CD13

38C12

PA0304-

Cytokeratin 17

E3

PA0114-

CD138 (Syndecan 1)

MI15

PA0088-

Cytokeratin 19

b170

PA0799

-

CD15

MMA

PA0473-

Cytokeratin 20

Ks20.8PA0022

PA0037

CD163

10D6

PA0090-

Cytokeratin 5

XM26

PA0468

-

CD19

BT51E

PA0843-

Cytokeratin 7

RN7

PA0942

PA0138

CD1a

MTB1

PA0235-

Cytokeratin 8

TS1

PA0567-

CD2 (LFA-2)

11F11

PA0271-

Cytokeratin, Multi (1/5/10/14)

34βE12

PA0134

-

CD20

L26

PA0200PA0359

Cytokeratin, Multi (AE1/AE3)

AE1/AE3

PA0094

-

CD21

2G9

PA0171-

Cytokeratin, Multi (AE1/AE3) 2

AE1/AE3

PA0909

-

CD22

FPC1

PA0249-DesminDE-R-11

PA0032

-

CD23

1B12

PA0169

-

DOG-1

K9

PA0219

-

CD25

4C9

PA0305-

E-Cadherin

36B5

PA0387

-

CD3

LN10

PA0553

PA0122

Epithelial Membrane Antigen

GP1.4

PA0035-

CD30

JCM182

PA0790-

Estrogen Receptor

6F11PA0151PA0009CD31 (PECAM-1)

JC70A

PA0414-

EZH2 (Enhancer of Zeste Homolog 2(Drosophila))

6A10

PA0575

-

CD33

PWS44

PA0555-

E980.1

PA0449-CD34 (Endothelial Cell Marker)

QBEnd/10

PA0212

PA0354

Factor XIIIa(Blood Coagulation Factor XIIIa)

CD4

4B12

PA0427-

FascinIM20

PA0420-* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

25

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B O N DB O N DR E A D Y - T O - U S E

A N T I B O D I E S

RT U SIMMUNOHISTOCHEMISTRY HAS NEVER BEEN EASIER
NAME

CLONE

7 ML

30 ML

NAME

CLONE

7 ML

30 ML

Galectin-3

9C4

PA0238-Myeloperoxidase

59A5

PA0491-

GastrinPolyclonal

PA0681-Myogenin (Myf-4)

LO26

PA0226-

Glial Fibrillary Acidic Protein

GA5PA0026-

Myoglobin

MYO18

PA0727-Granzyme B

11F1

PA0291-

Myosin Heavy Chain Antibodies

S131

PA0493-Gross Cystic Disease Fluid Protein-15

23A3

PA0708-

Napsin A

IP64

PA0064-

Human Chorionic Gonadotrophin (beta)

Polyclonal

PA0014-

Negative Control (Mouse)

MOPC-21

PA0996-

Negative Control (Rabbit)

n/aPA0777-

Neurofilament 200kD

N52.1.7

PA0371-

Neuron Specific Enolase

22C9

PA0435-

Oct-2

Oct-207

PA0532-Oct-3/4

N1NK

PA0193-p120 Catenin

EP66

PA0379

-

p16

6H12

PA0016-

p53 Protein

DO-7PA0057-

p63 Protein

7JUL

PA0103

-

Pax-5

1EW

PA0552

-

PD-L1

73-10

PA0832-

Placental Alkaline Phosphatase

8A9

PA0161-

Progesterone Receptor

16

PA0312-

Prostate Specific Antigen

35H9

PA0431-

Prostatic Acid Phosphatase

PASE/4LJ

PA0006-

Protein Gene Product 9.5

10A1

PA0286-

S-100B

EP32

PA0031-

Serotonin

Polyclonal

PA0736-

SMA (Alpha Smooth Muscle Actin)alpha sm-1

PA0943-

Synaptophysin

27G12

PA0299-2600000

PA0093-

Human Follicle Stimulating Hormone(beta 2) (HFSH)

INN-hFSH-60

PA0693-

Human Growth Hormone (HGH)

Polyclonal

PA0704-

Human Herpesvirus 8 (HHV8)

13B10

PA0050-Immunoglobulin D

DRN1C

PA0061-

Immunoglobulin G

RWP49

PA0905-

Immunoglobulin M

8H6

PA0278-Inhibin Alpha

R1

PA0488-Insulin

2D11-H5

PA0620-Kappa Light Chain

CH15

PA0606-

Ki67 Antigen

K2

PA0230-Ki67 Antigen

MM1

PA0118

PA0410Lambda Light Chain

SHL53

PA0570-Lysozyme (Muramidase)

Polyclonal

PA0391-

Mammaglobin

EP249

PA0378-Mast Cell Tryptase

10D11PA0019-Melan A

A103

PA0233PA0044

Melanoma Marker (HMB45)

HMB45

PA0027

PA0625Mesothelin

5B2

PA0373-

Mismatch Repair Protein (MLH1)

ES05

PA0610-Mismatch Repair Protein (MLH1)

ES05

PA0988-

Mismatch Repair Protein (MSH2)

25D12PA0048-

Tartrate-Resistant Acid Phosphatase(TRAP)

Mismatch Repair Protein (MSH2)

25D12

PA0989-Terminal Deoxynucleotidyl Transferase

SEN28

PA0339-Mismatch Repair Protein (MSH6)

EP49

PA0990-Thyroid Stimulating Hormone

QB2/6

PA0776-

Mismatch Repair Protein (PMS2)

EP51

PA0991-Thyroid Transcription Factor-1

SPT24

PA0364-

Muc-1 Glycoprotein

Ma695

PA0051-

Tyrosinase

T311

PA0322-

Muc-2 Glycoprotein

Ccp58

PA0155-Vimentin

V9

PA0640-

Muc-5AC Glycoprotein

CLH2

PA0052-36B11PA0055-

Muc-6 Glycoprotein

CLH5PA0053-von Willebrand Factor(Factor VIII-related antigen)

Multiple Myeloma Oncogene 1 (MUM-1)

EAU32

PA0129-Wilms' Tumor

WT49

PA0562-

Muscle Specific Actin

HHF35

PA0258-

Zap-70

L453R

PA0998-* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

26

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X L

F I S HP R O B E S

F O R

B O N D

2p23 ALK (2p23) Break

6q22 ROS1 (6q22) BreakAdenocarcinoma of the lung stained using Kreatech ALK (2p23) Break - XL probe for
BOND (KBI-XL001).

Adenocarcinoma of the lung stained using Kreatech ROS1 (6q22) Break - XL probe for
BOND (KBI-XL002).

ALK (2p23) BreakROS1 (6q22) BreakCODE
KBI-XL001

COLOR

FORMAT

Green/Red

2 x 1 mL
(10 x concentrate)

CODE

STATUSKBI-XL002

IVD

COLOR

FORMAT

Green/Red

2 x 1 mL
(10 x concentrate)

STATUS
IVD

MENU

MENU

LUNG PATHOLOGYLUNG PATHOLOGYBACKGROUNDBACKGROUND

ALK (2p23) Break - XL for BOND FISH probe detects genomic translocations
involving the ALK gene. ALK (2p23) Proximal - XL and ALK (2p23) Distal - XLprobes are optimized to detect the genomic regions proximal and distal tobreak points in the ALK gene region.

ROS1 (6q22) Break - XL for BOND FISH probe detects genomic translocations
involving the ROS1 gene. ROS1 (6q22) Proximal - XL and ROS1 (6q22) Distal XL probes are optimized to detect the genomic regions proximal and distal tobreak points in the ROS1 gene region.

When combined, both probes are used to detect translocations involving the
ALK gene at 2p23.

When combined, both probes are used to detect translocations involving the
ROS1 gene at 6q22.

RH56671
2p23

310 kB
SHGC-14420

SHGC-17159
SHGC-83664

ALK

340 kB

450 kB

SHGC-144661

RH69070

ROS1

RH104060

Exon 42
Exon 30

6q22

260 kB
RH68126

GOPC

6
2* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

27

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X L

F I S HP R O B E S

F O R

B O N D

7q31 MET (7q31) / SE7 (D7Z1)

8p11 FGFR1 (8p11) / SE8 (D8Z1)

Adenocarcinoma of the lung stained using Kreatech MET (7q31) / SE7(D7Z1) - XL probe
for BOND (KBI-XL003).

Squamous cell carcinoma of the lung stained using Kreatech FGFR1 (8p11) / SE8 (D8Z1)- XL probe for BOND (KBI-XL004).

MET (7q31) / SE7 (D7Z1)

FGFR1 (8p11) / SE8 (D8Z1)

CODE
KBI-XL003

COLOR

FORMAT

Green/Red

2 x 1 mL
(10 x concentrate)

CODE

STATUSKBI-XL004

IVD

COLOR

FORMAT

Green/Red

2 x 1 mL
(10 x concentrate)

STATUS
IVD

MENU

MENU

LUNG PATHOLOGYLUNG PATHOLOGYBACKGROUNDBACKGROUND

MET (7q31) / SE7 (D7Z1) - XL for BOND FISH probe detects genomic
amplifications involving the MET gene. MET (7q31) - XL is optimized to detect
copy numbers of the MET gene region at 7q31. SE7 (D7Z1) - XL is optimized todetect copy numbers of the chromosome 7 centromere.

The FGFR1 (8p11) / SE8 (D8Z1) - XL for BOND probe detects genomic
amplifications involving the FGFR1 gene. FGFR1 (8p11) - XL is optimized todetect copy numbers of the FGFR1 gene at 8p11. SE8 (D8Z1) - XL is optimized
to detect copy numbers of the chromosome 8 centromere.

When combined, both probes are used to detect amplification of the MET gene
at 7q31, using the centromeric probe as a control.

When combined, both probes are used to detect amplification of the FGFR1
gene at 8p11, using the centromeric probe as a control.

RH46977
8p11.2

D7Z1

SE8
FGFR1

540 kB

D7S3086

7q31

MET

D8S414450 kB

SHGC-79904

87* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

28

A D V A N C E D

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X L

F I S HP R O B E S

F O R

B O N D

10q11 RET (10q11) Break

8q24 MYC (8q24) BreakAdenocarcinoma of the lung stained using Kreatech RET (10q11) Break - XL probe for
BOND (KBI-XL005).

Diffuse Large B-Cell Lymphoma stained using Kreatech MYC (8q24) Break - XL probe for
BOND (KBI-XL006).

RET (10q11) Break

MYC (8q24) BreakCODE
KBI-XL005

COLOR

FORMAT

Green/Red

2 x 1 mL
(10 x concentrate)

CODE

STATUSKBI-XL006

IVD

COLOR

FORMAT

Green/Red

2 x 1 mL
(10 x concentrate)

STATUS
IVD

MENU

MENU

LUNG PATHOLOGYHEMATOPATHOLOGY (LYMPHOMA)

BACKGROUNDBACKGROUND

RET (10q11) Break - XL for BOND FISH probe detects genomic translocations
involving the RET gene. RET (10q11) Proximal - XL and RET (10q11) Distal - XLprobes are optimized to detect the genomic regions proximal and distal tobreak points in the RET gene region.

MYC (8q24) Break - XL for BOND FISH probe detects genomic translocations
involving the MYC gene. MYC (8q24) Proximal - XL and MYC (8q24) Distal - XL
are optimized to detect the genomic regions proximal and distal to breakpoints in the MYC gene region.

When combined, both probes are used to detect translocations involving the
RET gene at 10q11.

When combined, both probes are used to detect translocations involving the
MYC gene at 8q24.

RH51277
SHGC-104746

535 kB

680 kB

RET

10q11.2GDB:579598

RH77966

D10S1176

MYC

500 kB

SHGC-100242

SHGC-148579

8q24.210

8

540 kB

SHGC-140863* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

29

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X L

F I S HP R O B E S

F O R

B O N D

14q32 IGH (14q32) Break

18q21 BCL2 (18q21) BreakDiffuse Large B-Cell Lymphoma stained using Kreatech IGH (14q32) Break - XL probe for
BOND (KBI-XL007).

Diffuse Large B-Cell Lymphoma stained using Kreatech BCL2 (18q21) Break - XL probe
for BOND (KBI-XL008).

IGH (14q32) BreakBCL2 (18q21) BreakCODE
KBI-XL007

COLOR

FORMAT

Green/Red

2 x 1 mL
(10 x concentrate)

CODE

STATUSKBI-XL008

IVD

COLOR

FORMAT

Green/Red

2 x 1 mL
(10 x concentrate)

STATUS
IVD

MENU

MENU

HEMATOPATHOLOGY (LYMPHOMA)

HEMATOPATHOLOGY (LYMPHOMA)

BACKGROUNDBACKGROUND

IGH (14q32) Break - XL for BOND FISH probe detects genomic translocations
involving the IGH gene. IGH (14q32) Proximal - XL and IGH (14q32) Distal - XLprobes are optimized to detect the genomic regions proximal and distal tobreak points in the IGH gene region.

BCL2 (18q21) Break - XL for BOND FISH probe detects genomic translocations
involving the BCL2 gene. BCL2 (18q21) Proximal - XL and BCL2 (18q21) Distal- XL probes are optimized to detect the genomic regions proximal and distal tobreak points in the BCL2 gene region.

When combined, both probes are used to detect translocations involving the
IGH gene at 14q32.

When combined, both probes are used to detect translocations involving the
BCL2 gene at 18q21.
RH75060

480 kB

D14S683E
D18S91660 kB

BCL2
18q21

RH44825

D18S87540 kB

IGH
SHGC-170017
14q32

14

18

460 kB

SHGC-4651

D14S1420* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

30

A D V A N C E D

S T A I N I N G–

X L

F I S HP R O B E S

F O R

B O N D

3q27 BCL6 (3q27) Break

17p13 TP53 (17p13) / SE 17

Diffuse Large B-Cell Lymphoma stained using Kreatech BCL6 (3q27) Break - XL probe for
BOND (KBI-XL009).

Diffuse Large B-Cell Lymphoma stained using Kreatech TP53 (17p13) / SE17 - XL probe
for BOND (KBI-XL010).

BCL6 (3q27) BreakTP53 (17p13) / SE 17

CODE
KBI-XL009

COLOR

FORMAT

Green/Red

2 x 1 mL
(10 x concentrate)

CODE

STATUSKBI-XL010

IVD

COLOR

FORMAT

Green/Red

2 x 1 mL
(10 x concentrate)

STATUS
IVD

MENU

MENU

HEMATOPATHOLOGY (LYMPHOMA)

HEMATOPATHOLOGY (LYMPHOMA)

BACKGROUNDBACKGROUND

BCL6 (3q27) Break - XL for BOND FISH probe detects genomic translocations
involving the BCL6 gene. BCL6 (3q27) Proximal - XL and BCL6 (3q27) Distal XL probes are optimized to detect the genomic regions proximal and distal tobreak points in the BCL6 gene region.

TP53 (17p13) / SE 17 - XL for BOND FISH probe detects genomic deletions
involving the TP53 gene. TP53 (17p13) - XL is optimized to detect copy
numbers of the TP53 gene region at 17p13. SE 17 (D17Z1) - XL is optimized todetect copy numbers of the chromosome 17 centromere.

When combined, both probes are used to detect translocations involving the
BCL6 gene at 3q27.

When combined, both probes are used to detect deletion of the TP53 gene at
17p13, with the centromeric probe as a control.
17p13
D17S960

D17Z1

335 kB
TP53

D17S634

17

D3S4060

540 kB
SHGC-143921

BCL6

MBR*
ABR*

SHGC-60245

410 kB

3q27

3

SHGC-7226

ABR* atypical breakpoint region
MBR* major breakpoint region* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

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BOND Kappa Probe
FORMAT
5.5 mL

O

N

D

C

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P

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B

E

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BOND Lambda Probe

CODE
PB0645B

USAGE
PSTATUSFORMAT
5.5 mL

IVD

CODE
PB0669USAGE

STATUSPIVDBACKGROUNDBACKGROUND

Kappa Probe is used for the qualitative identification of Kappa light chain
messenger RNA (mRNA) in formalin-fixed, paraffin-embedded tissue by
in situ hybridization (ISH) using the automated BOND system.

Lambda Probe is used in conjunction with Kappa Probe for the detectionof antibody producing B cells in formalin-fixed, paraffin-embedded tissue.
B cell neoplasms are thought to arise from a single transformed cell(monoclonal), whereas reactive states result in proliferation of a numberof B cells (polyclonal).

Immunoglobulins are glycoproteins produced in mature B-cells against
a specific antigen. Each individual immunoglobulin molecule comprises
two heavy and two light polypeptide chains. There are five classes of
immunoglobulin, determined by the type of heavy chain.

Since immunoglobulins from the same B cell contain either Kappa or Lambda
light chains, light chain restriction or monoclonality can be used to make thedistinction between reactive and neoplastic B cell proliferations.

In contrast, there are only two types of light chain: Kappa or Lambda.
Each individual immunogloblin molecule is composed of one of five classesof heavy chains and either Kappa or Lambda light chains. In normal human
lymphoid populations, the ratio of Kappa to Lambda light chainsis approximately 2:1.

RESTRICTIONS
PB0669 is not available for sale in the US.

B-cell neoplasms are thought to arise from a single transformed cell(monoclonal). In contrast, reactive states result in proliferation of a numberof B-cells (polyclonal). Since immunoglobulins from the same B-cell containeither Kappa or Lambda light chains, light chain restriction or monoclonality
can be used to make the distinction between reactive and neoplastic B cellproliferations.
Kappa Probe is used in conjunction with Lambda Probe for the detectionof antibody producing B-cells in formalin-fixed, paraffin embedded tissue.
RESTRICTIONS
PB0645 is not available for sale in the US.
Human tonsil: in situ hybridization for lambda mRNA using Lambda Probe, AntiFluorescein Antibody and BOND Polymer Refine Detection.

Human tonsil: in situ hybridization for kappa mRNA using Kappa Probe, Anti-Fluorescein
Antibody and BOND Polymer Refine Detection.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

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BOND EBER Probe
FORMAT
5.5 mL

B

O

N

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BOND CMV Probe
CODE

PB0589USAGEPSTATUSFORMAT
5.5 mL

IVD

CODE
PB0614USAGE

STATUSPBACKGROUNDBACKGROUND

Epstein-Barr Virus (EBV) is a member of the Gamma Herpes Virus family.
EBV can establish both lytic infection as well as latent infection.

Cytomegalovirus (CMV) is a member of the Beta Herpes Virus family,transmitted via body fluids, and can establish primary infection, latent
infection and subsequent viral reactivation.

Epstein-Barr Virus encoded RNA (EBER) is abundantly expressed in latent EBV
infection and ISH is considered a sensitive method for the detection of latent
EBV infection.

IVD

CMV is a common opportunistic pathogen, capable of causing serious
disease in immunocompromised individuals such as AIDS patients, transplantpatients and in neonates.

Latent EBV infection is associated with several conditions including: Hodgkin’s
Lymphoma, B cell Non Hodgkin’s Lymphoma, nasopharyngeal carcinoma,
lymphoproliferative disorders and lymphoma in the immunosuppressed,
including transplant and AIDS patients, gastric cancer and some T cell
lymphomas.

Congenital CMV is a result of intrauterine infection and although the majorityof children are asymptomatic, congenital CMV can result in sensorineural
hearing loss, cognitive, motor and visual deficits and seizures.
RESTRICTIONSRESTRICTIONS

PB0614 is not available for sale in the US.

PB0589 is not available for sale in the US.

Human placenta: in situ hybridization for Cytomegalovirus (CMV) mRNA using CMVProbe, Anti-Fluorescein Antibody and BOND Polymer Refine Detection.

Hodgkin’s lymphoma: in situ hybridization for Epstein-Barr virus (EBV) encoded mRNA
using EBV Probe, Anti-Fluorescein Antibody and BOND Polymer Refine Detection.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

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BOND HPV (subtypes 6, 11) Probe
FORMAT
6.25 mL

CODE
PB0780

USAGE
P

B

O

N

D

C

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S

H

P

R

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B

E

S

BOND HPV (subtypes 16, 18, 31, 33,
51) Probe

STATUSFORMAT

IVD

6.25 mL

CODE
PB0829USAGEPSTATUSIVDBACKGROUNDBACKGROUNDHPV Probe (Subtypes 6,11) is used for the qualitative identification of the
Human Papillomavirus (HPV) DNA in formalin-fixed, paraffin-embedded tissue
by in situ hybridization (ISH) using the automated BOND system.
This probe binds to HPV subtypes 6 and 11 and is biotin-conjugated.

HPV Probe (Subtypes 16, 18, 31, 33, 51) is used for the qualitative
identification of the Human Papillomavirus (HPV) DNA in formalin-fixed,
paraffin-embedded tissue by in situ hybridization (ISH) using the automated
BOND system. This probe binds to HPV 16, 18, 31, 33 and 51 and is biotinconjugated.

There are over 100 known Human Papillomavirus types, but only about 40 are
known to infect the anogenital epithelium. HPV is the most common sexuallytransmitted virus. HPV infections have been associated with a number ofmalignant and benign lesions, including genital warts, anogenital cancers andoral head and neck cancers. HPV subtypes have been associated with over
95% of cervical cancers. As a result, HPV subtypes are broadly classified ashigh or low risk, depending on the incidence they are associated with cervicalmalignant transformation (high risk) and benign lesion development (low risk).
There are 12 HPV subtypes classified as low risk, including 6 and 11, whichhave a low association with cervical cancer progression.

There are over 100 known Human Papillomavirus types, but only about 40 are
known to infect the anogenital epithelium. HPV is the most common sexuallytransmitted virus. HPV infections have been associated with a number ofmalignant and benign lesions, including genital warts, anogenital cancers andoral head and neck cancers. HPV subtypes have been associated with over
95% of cervical cancers. As a result, HPV subtypes are broadly classified ashigh or low risk, depending on the incidence they are associated with cervicalmalignant transformation (high risk) and benign lesion development (lowrisk). There are 15 HPV subtypes classified as high risk, including 16, 18,
31, 33 and 51, but HPV subtypes 16 and 18 are the most frequent subtypes
associated with cervical carcinogenesis and are detected in up to 71% ofcervical cancers. It is now widely accepted that a HPV infection is necessary
for cervical cancer progression; however, additional cellular events, such as
HPV DNA integration status and viral load, are also key factors associatedwith cancer progression.

RESTRICTIONS
PB0780 is not available for sale in the US.

RESTRICTIONS
PB0829 is not available for sale in the US.

Cervical tissue (CIN1): in situ hybridization for HPV, subtype 6 and 11 DNA using HPV(6,11) Probe, Anti-Biotin Antibody, Stringency Wash and BOND Polymer Refine Detection.

Cervical tissue, abnormal epithelia (CINII) stained with HPV (subtypes 16, 18, 31,33, 51)
Probe Anti-Biotin Antibody, Stringency Wash and BOND Polymer Refine Detection.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

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BOND DNA Positive Control
FORMAT
6.25 mL

CODE
PB0682

USAGE
P

B

O

N

D

C

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S

H

P

R

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B

E

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BOND RNA Positive Control Probe
STATUSFORMAT
5.5 mL

IVD

CODE
PB0785USAGEP

STATUSIVDBACKGROUNDBACKGROUND

Positive control probes should be run on patient tissue to validate reagent
performance, to provide information on the preservation of nucleic acids in thetissue and to confirm accessibility of nucleic acids to the probe.

RNA is very susceptible to degradation by RNases, therefore, theRNA Positive Control Probe is ideally used as a screening tool to detect
the preservation of mRNA in cells.

The DNA Positive Control Probe is intended for use as a positive control informalin-fixed, paraffin-embedded tissue by DNA in situ hybridization (ISH)using the automated BOND system.

RESTRICTIONS
PB0785 is not available for sale in the US.

It is designed to specifically hybridize to the genomic ALU repeat sequences,which represent approximately 10% of the human genome. The DNA Positive
Control Probe is biotin-labeled.

BOND RNA Negative Control Probe
FORMAT

RESTRICTIONS
5.5 mLPB0682 is not available for sale in the US.

CODE
PB0809USAGEPSTATUSIVDBACKGROUND

BOND DNA Negative Control
FORMAT
6.25 mL

CODE
PB0731USAGEP

RNA Negative Control Probe is intended for use in the identification of
background staining resulting from non-specific interactions in formalin-fixed,
paraffin-embedded tissue by in situ hybridization (ISH) using the automated
BOND system.

STATUSIVD

RNA Negative Control Probe is a single oligonucleotide, designed from zebra
fish DNA and analyzed using Basic Local Alignment Search Tool (BLAST)
analysis to confirm that the sequence bears no homology with any humansequences. The RNA Negative Control Probe is generated with a fluoresceinlabel using the same procedures as applied to other oligonucleotide probes
used in the detection of RNA on BOND. Therefore, RNA Negative Control Probeis ideal as a negative control probe for RNA ISH on BOND.

BACKGROUND
The DNA Negative Control is intended for use as a negative control informalin-fixed, paraffin-embedded tissue by DNA in situ hybridization (ISH)using the automated BOND system.
DNA Negative Control is used in place of the probe, to enable the identificationof background staining resulting from non-specific interactions with thespecimen sample under investigation.

RESTRICTIONS
PB0809 is not available for sale in the US.

RESTRICTIONS
PB0731 is not available for sale in the US.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

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BOND Dewax Solution
FORMAT
1L

O

N

D

A

N

C

I

L

L

A

R

I

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S

BOND Wash Solution 10X Concentrate

CODE
AR9222B

USAGE
PSTATUSFORMAT
1L

IVD

CODE
AR9590USAGEPSTATUSIVDAPPLICATIONAPPLICATIONThe use of BOND Dewax Solution allows paraffin wax to be removed fromtissue sections before rehydration and staining on BOND. It is speciallyformulated to be compatible with the automated BOND system, and efficiently
removes wax from slides while retaining the integrity of tissue antigens andprobe binding sites. BOND Dewax Solution is less harmful than alternative
deparaffinization solutions such as xylene.

BOND Wash Solution is the only wash buffer that should be used in BOND
automated staining procedures. It is formulated for optimal reagent flow underthe BOND Covertile to help ensure that excess reagent is removed from thetissue section before new reagent is added.
COMPONENTS
BOND Wash Solution 10X Concentrate is a concentrated buffer solution
specifically for use on the automated BOND system. It is available in 1 L
quantities, and when diluted will make up 10 L of working solution.

COMPONENTS
BOND Dewax Solution is a deparaffinization solution specifically designed foruse on the automated BOND system. It is provided ready-to-use in 1 L bottles
and can be poured directly into the appropriate bulk reagent container on the
instrument.

BOND Wash Solution 10X Concentrate.

BOND Dewax Solution.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

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BOND Epitope Retrieval Solution 1
FORMAT
1L

CODE
AR9961

USAGE
P

B

O

N

D

A

N

C

I

L

L

A

R

I

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BOND Epitope Retrieval Solution 2

STATUSFORMAT
1L

IVD

CODE
AR9640USAGEPSTATUSIVDAPPLICATIONAPPLICATION

BOND Epitope Retrieval Solution 1 is for use on formalin-fixed, paraffinembedded tissue sections to expose epitopes within tissue that have beenmasked during fixation. The solution is gentle on sections as it has a reduced
boiling temperature and utilizes BOND Covertile technology to prevent reagent
evaporation.

BOND Epitope Retrieval Solution 2 is for use on formalin-fixed, paraffinembedded tissue sections to expose epitopes within tissue that have beenmasked during fixation. The solution is gentle on sections as it has a reduced
boiling temperature and utilizes BOND Covertile technology to prevent reagent
evaporation.

COMPONENTSCOMPONENTS

BOND Epitope Retrieval Solution 1 is a 1 L ready-to-use, citrate-based
pH 6.0 solution. It is specifically for heat-induced epitope retrieval (HIER)on the automated BOND system.

BOND Epitope Retrieval Solution 2 is a 1 L ready-to-use, EDTA-based pH 9.0
solution. It is specifically for heat-induced epitope retrieval (HIER) on the
BOND system.

Human lung stained for TTF-1 with BOND Ready-to-Use Thyroid Transcription Factor-1(SPT24, PA0364), using BOND Polymer Refine Detection and BOND Epitope Retrieval
Solution 1.

Human tonsil stained for CD3 with BOND Ready-to-Use CD3 (LN10, PA0533), using BOND
Polymer Refine Detection and BOND Epitope Retrieval Solution 2.

BOND Epitope Retrieval Solution 2.

BOND Epitope Retrieval Solution 1.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

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BOND Universal Covertile
FORMAT
160 Pack

CODE
S21.4611

O

N

D

A

N

C

I

L

L

A

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I

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BOND Primary Antibody Diluent
USAGE

P

B

STATUSFORMAT
500 mL

IVD

CODE
AR9352USAGE
P

STATUSIVDAPPLICATIONAPPLICATIONThe BOND Universal Covertile is a patented technology that facilitates gentle,
even reagent flow over tissue. It prevents reagent evaporation and minimizes
waste generation. The Covertile is re-usable and can also be recycled once its
staining life is over.

BOND Primary Antibody Diluent is specifically for diluting concentrated
primary antibodies for use on the automated BOND system. It is not intended
for the reconstitution of lyophilized reagents.
COMPONENTS
BOND Primary Antibody Diluent is ready-to-use and available in a quantityof 500 mL.

BOND Universal Covertile.

BOND Primary Antibody Diluent.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

38

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BOND Enzyme Pretreatment Kit
FORMAT
1 Kit

CODE
AR9551

USAGE
P

B

O

N

D

A

N

C

I

L

L

A

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BOND DAB Enhancer
STATUSFORMAT
30 mL

IVD

CODE
AR9432USAGE
P

STATUSIVDAPPLICATIONAPPLICATION

Immunohistochemistry (IHC)

BOND DAB Enhancer changes the color of the DAB reaction deposit fromgolden to dark brown, providing an increase in contrast between chromogenspecific staining and the slide back drop. This can assist in qualitative
identification of antigens.

The BOND Enzyme Pretreatment Kit can be used for enzymatic digestion
on formalin-fixed, paraffin-embedded tissue sections to assist in epitope
exposure. Enzymatic pretreatment improves the staining of some antibodies
by exposing epitopes within tissue that have been masked during fixation.

COMPONENTS
BOND DAB Enhancer is a heavy metal solution for use on the automated BOND
system. The no-mix, ready-to-use format simplifies laboratory workflow.

In situ Hybridization (ISH)The diluted enzyme solution can also be used for ISH. Enzymatic digestion oftissue assists in the penetration of probes and facilitates binding.
COMPONENTS• BOND Enzyme Concentrate, 1 mL
• BOND Enzyme Diluent, 200 mL• 3 x BOND Open Containers, 7 mL
The enzyme is diluted before use in the BOND Open Containers supplied.
The diluted enzyme solution is used for enzymatic digestion on the automated
BOND system.

BOND DAB Enhancer.

BOND Enzyme Pretreatment Kit.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

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BOND Anti-Fluorescein Antibody
FORMAT

CODE

USAGE

B

O

N

D

A

N

C

I

L

L

A

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BOND Hybridization Solution
STATUSFORMAT

CODE

USAGE

STATUS3.75 mL

AR0833P

IVD

100 mL

AR9037

-

IVD

15 mL

AR0222P

IVD

100 mLAR9013-RUO

APPLICATIONAPPLICATION

In situ hybridization (ISH) allows the detection and visualization of specificnucleic acids in tissues sections. ISH probes used for the detection of mRNAor DNA on BOND contain a fluorescein label. The BOND Anti-Fluorescein
Antibody allows linking of the oligonucleotide probe with the detection
reagents, and consequently, visualization of a chromogenic product by lightmicroscopy.

BOND Hybridization Solution is intended to be used for the dilution ofindividual In situ hybridization (ISH) probes for use on the automated BOND
system.

BOND Anti-Biotin Antibody
FORMATCOMPONENTS

7.5 mL

BOND Anti-Fluorescein Antibody is a purified IgG fraction of a mousemonoclonal antibody. It is supplied ready-to-use.

CODE
AR0584USAGE
P

STATUSIVDAPPLICATION
In situ hybridization (ISH) allows the detection and visualization of specificnucleic acids in tissue sections. Some ISH probes used for detection of DNA
on the BOND system contain a biotin label. The Anti-Biotin Antibody allows thelinking of the probe with the detection reagents and consequently visualizationof a chromogenic product by light microscopy.
COMPONENTS
Anti-Biotin Antibody is a purified anti-biotin, IgG1 isotype. It is supplied readyto-use.

Anti-Biotin Antibody* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

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BOND Stringency WashFORMAT
3.75 mL

O

N

D

A

N

C

I

L

L

A

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BOND RNAscope Protease

CODE
AR0633B

USAGE
P

STATUSFORMAT
12 mL

IVD

CODE
AR9773USAGE
P

STATUSGPRAPPLICATIONAPPLICATION

In situ hybridization (ISH) allows the detection and visualization of specificnucleic acids in tissue sections. The BOND Stringency Wash Solution isintended for use with DNA probes to reduce non-specific DNA hybridization informalin-fixed, paraffin-embedded tissue using the automated BOND system.
COMPONENTS

The BOND RNAscope Protease reagent is used for pretreatment of FFPE
(formalin fixed, paraffin-embedded) tissue in conjunction with BOND reagentson the automated BOND-III system. The enzyme pretreatment permeabilizes
the tissue and prepares the sample for hybridization witha target RNA specific oligonucleotide probe and subsequent detection
using the BOND RNAscope Detection Reagents.

The BOND Stringency Wash Solution is a formamide mixture used with the
BOND DNA ISH Probes. This solution reduces non-specific hybridization of
DNA probes.

Total volume = 12 mL, sufficient for 60 tests.

COMPONENTS

BOND RNAscope Protease is ready to use. Reconstitution, mixing, dilution
or titration of this reagent is not required.

Stringency Wash.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

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BOND Aspirating Probe Cleaning
SystemFORMAT
15 Cleaning Cycles

CODE
CS9100

USAGE
-

B

O

N

D

C

O

N

S

U

M

A

B

L

E

BOND Open Containers 7 mL
STATUS-FORMAT

CODE

10 Pack, Minimum
200 Tests/Container

OP79193

USAGE-

STATUSIVD

PRODUCT DESCRIPTIONPRODUCT DESCRIPTION

BOND Open 7 mL Containers allow the use of reagents from any source on the
BOND system. Each container can be refilled until a total of 40 mL has beendispensed from it. They are ideal for reagents that are consumed intermittently
and have a short shelf life.

The BOND Aspirating Probe Cleaning System contains reagents optimized toclean the aspirating probe of residual DAB. Sold in a standard reagent tray, thesystem is loaded onto BOND where a predefined cleaning protocol ensuresmaximum wash efficiency.

BOND Mixing Stations
FORMAT
5 PackS

CODE
S21.1971

USAGE-

STATUSIVD

PRODUCT DESCRIPTION
BOND Mixing Stations are reusable inserts with six vials for mixing andcatalyzing chromogens prior to slide application. Fresh chromogen promotes
high quality staining. Replacing the mixing stations at recommended intervals
ensures that the mixed chromogen does not become contaminated.

BOND Open Containers 7 mL.

BOND Open Containers 30 mL
FORMAT

CODE

10 Pack, Minimum
200 Tests/Container

OP309700

USAGE-

STATUSIVD

PRODUCT DESCRIPTION
BOND Open 30 mL Containers allow the use of reagents from any sourceon the BOND system. Each container holds 30 mL and can be refilled until a
total of 40 mL has been dispensed from it. They are ideal for high throughput
reagents that are consumed on a daily basis and their use can minimize
reagent preparation time.

BOND Mixing Stations.

BOND Open Containers 30 mL.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

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BOND Titration Kit
FORMAT
10 Titration Containers and
50 Titration Container Inserts

B

O

N

D

C

O

N

S

U

M

A

B

L

E

BOND Slide Label and Print Ribbon Kit
CODE

OPT9049

USAGE-

STATUSIVD

PRODUCT DESCRIPTION
The BOND Titration Kit contains BOND Titration Container Inserts and BOND
Titration Containers. The kit allows users to optimize primary antibody
concentrates on the BOND system. The kits can be re-used for different
antibodies and are designed with minimal dead volume to preserve reagent.

FORMAT

CODE

USAGE

STATUS

1 Pack, 3000 Labels

S21.4564

Zebra

IVD

1 Pack, 3000 Labels

S21.4604

Cognitive

IVD

6 Pack, 18000 Labels

S21.4610

Cognitive

IVD

PRODUCT DESCRIPTION
The BOND Slide Label and Print Ribbon Kit produces high-quality, solventresistant slide labels for use on the BOND system. This assists in preserving
the integrity of slide identification and patient data records on BOND slides.
The BOND Universal Slide labels adhere to slides for easy and secure
identification.

BOND Titration Kit.

BOND Titration Container Inserts
FORMAT
50 Pack

CODE
OPT9719

USAGE-

BOND Slide Label and Print Ribbon Kit.

STATUS

BOND Reagent Tray

IVD

FORMATPRODUCT DESCRIPTION

1 Tray

BOND Titration Container Inserts are tubes that fit directly into the BOND
Titration Containers. They enable use of up to 40 mL of reagent per titration
container.

CODE
S21.1003

USAGE-

STATUS-PRODUCT DESCRIPTION
Additional BOND Reagent Trays let laboratories setup reagents for upcoming
runs while other reagent trays are in use. This reduces setup delays andimproves laboratory workflow.

BOND Titration Container Inserts.

BOND Reagent Tray.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

43

S

A

D

V

A

N

C

E

D

S

T

A

I

N

I

N

G

–

BOND Slide Tray
FORMAT
1 Tray

B

O

N

D

C

O

N

S

U

M

A

B

L

E

S

BOND Syringe (for 9-Port Pump)
CODE
S21.4586

USAGE-

STATUSFORMAT

-

CODE

USAGE

STATUS

1 Syringe

S21.2131--

4 Syringes

S21.4565P-PRODUCT DESCRIPTIONPRODUCT DESCRIPTION

The BOND slide tray offers keying cues to improve usability and Covertile
placement. Additional BOND Slide Trays to allow laboratories to prepare
slides while other trays are running. This reduces setup delays and improves
laboratory workflow. This tray can be used with all BOND Covertiles.

The BOND Syringe precisely measures reagent volumes to be dispensed onto
the slides. The syringe must be replaced at regular intervals as prompted by
the software or if problems are found during scheduled fluidics checks. Thispart is for BOND-MAX instruments with a 9-Port valve.

BOND Slide Tray.
BOND Syringe.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

44

A

D

V

A

N

C

E

D

S

T

A

I

N

I

N

G

–

20 Boxes x 72 Slides/Box

O

N

D

C

O

N

S

U

M

A

B

L

E

S

BOND Covertile Cleaning Rack

BOND Plus Slides
FORMAT

B

CODE
S21.2113

USAGE
P

FORMATSTATUS
1 Rack

IVD

CODE
S21.4588

USAGE-

STATUS-PRODUCT DESCRIPTIONPRODUCT DESCRIPTION

BOND Plus Slides are positively charged glass microscopic slides designed foruse on the BOND system. They include defined margins to enable the accurate
placement of tissue for staining in the 100 µL and the 150 µL dispense modes,
which helps in maintaining the integrity of staining quality.

The BOND Covertile Cleaning Rack makes Covertile cleaning even easier. It iseasy to load, securely locks the Covertiles in place, and sits either vertically or
horizontally.

BOND Covertile Cleaning Rack.
BOND Plus Slides.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

45

MANUALNOVOLINK MAX POLYMER DETECTION SYSTEM ..................................... 47

HEMATOXYLIN ........................................................................................... 48

NOVOLINK POLYMER DETECTION SYSTEM.............................................. 47

PEROXIDASE DETECTION SYSTEMS (READY-TO-USE) ............................. 48

NOVOLINK MIN POLYMER DETECTION SYSTEM....................................... 47

STREPTAVIDIN-HRP ................................................................................... 49

PEROXIDASE BLOCK .................................................................................. 47

AVIDIN/BIOTIN BLOCKING SYSTEM .......................................................... 49

PROTEIN BLOCK ......................................................................................... 47

ANTIBODY DILUENT.................................................................................... 50

NOVOLINK MAX POLYMER ........................................................................ 48

ENZYME PROTEINASE K (IHC)................................................................... 50

NOVOLINK POLYMER ................................................................................. 48

EPITOPE RETRIEVAL SOLUTIONS PH6 ..................................................... 50

NOVOLINK MAX DAB (POLYMER) .............................................................. 48

EPITOPE RETRIEVAL SOLUTIONS PH9 ..................................................... 51

NOVOLINK DAB (POLYMER) ....................................................................... 48

MANUAL ANCILLARIES - MOLECULAR...................................................... 52

46

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M A N U A L

Novolink Max Polymer
Detection System
FORMAT
1250 Tests

-

I H C

Novolink Min Polymer
Detection System

CODE
RE7280-K

D E T E C T I O N

USAGE
P

STATUSFORMAT
50 Tests

IVD

CODE
RE7290-K

USAGE
P

STATUSIVD

PRODUCT DESCRIPTIONPRODUCT DESCRIPTIONThe Novolink Polymer Detection Systems utilize a novel Compact Polymer
technology. Therefore, the problem of non-specific staining that can occur
with Streptavidin/Biotin detection systems due to endogenous biotin does
not occur. Novolink Polymer Detection Systems contain pre-diluted, reagentsin color coded bottles for ease of use and ultimate convenience. Thesesystems can be used for the visualization of mouse IgG, mouse IgM andrabbit IgG primary antibodies. These detection systems contain Peroxidase
Block, Protein Block, Post Primary Block, Novolink Polymer, DAB Chromogen,
Novolink DAB Substrate Buffer (Polymer) and Hematoxylin.

The Novolink Polymer Detection Systems utilize a novel Compact Polymer
technology. Therefore, the problem of non-specific staining that can occur
with Streptavidin/Biotin detection systems due to endogenous biotin does
not occur. Novolink Polymer Detection Systems contain pre-diluted, reagentsin color coded bottles for ease of use and ultimate convenience. Thesesystems can be used for the visualization of mouse IgG, mouse IgM andrabbit IgG primary antibodies. These detection systems contain Peroxidase
Block, Protein Block, Post Primary Block, Novolink Polymer, DAB Chromogen,
Novolink DAB Substrate Buffer (Polymer) and Hematoxylin.

Peroxidase Block
FORMAT
25 mL

CODE
RE7101USAGE
PSTATUSIVD

PRODUCT DESCRIPTION
Novocastra Peroxidase Block, RE7101, is intended for use in the peroxidase
based immunohistochemical (IHC) staining procedures. The presence ofpseudoperoxidase (erythrocytes) and endogenous peroxidase in paraffin
sections to be stained by immunoperoxidase procedures, can result in
nonspecific staining. A method for the blocking of pseudoperoxidase wasdescribed (StreefkerkJG, Journal of Histochemistry and Cytochemistry. 20:
829 (1972)). This product is used in a peroxidase based IHC procedure.
Incubating sections with Novocastra Peroxidase Block, RE7101, can neutralize
endogenous peroxidase activity. 25 mL of reagent is supplied.

Novolink Polymer Detection System (RE7150-K) staining for Cytokeratin 5 with NCL-L-CK5
on breast carcinoma. Paraffin section.

Novolink Polymer
Detection System
FORMAT

CODE

USAGE

Protein BlockSTATUS

250 Tests

RE7140-K

P

IVD

500 Tests

RE7150-K

P

IVD

FORMAT
25 mL

CODE
RE7102USAGE
P

STATUSIVD

PRODUCT DESCRIPTIONPRODUCT DESCRIPTIONThe Novolink Polymer Detection Systems utilize a novel Compact Polymer
technology. Therefore, the problem of non-specific staining that can occur
with Streptavidin/Biotin detection systems due to endogenous biotin does
not occur. Novolink Polymer Detection Systems contain pre-diluted, reagentsin color coded bottles for ease of use and ultimate convenience. Thesesystems can be used for the visualization of mouse IgG, mouse IgM andrabbit IgG primary antibodies. These detection systems contain Peroxidase
Block, Protein Block, Post Primary Block, Novolink Polymer, DAB Chromogen,
Novolink DAB Substrate Buffer (Polymer) and Hematoxylin.

Novocastra Protein Block, RE7102, is intended for use inimmunohistochemical (IHC) staining procedures. In immunohistochemistry,diffuse non-specific staining (background) may occur as a result ofhydrophobic and ionic interactions between antibodies and tissue
components. Novocastra Protein Block, RE7102, is a serum-free, protein
blocker. 25 mL of reagent is supplied.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

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M A N U A L

Novolink Max Polymer
FORMAT
1250 Tests

-

I H C

Novolink DAB (Polymer)

CODE
RE7260-K

D E T E C T I O N

USAGE
P

STATUSFORMAT
250 Tests

IVD

CODE
RE7230-K

USAGE
P

STATUSIVD

PRODUCT DESCRIPTIONPRODUCT DESCRIPTION

Novolink (Polymer), RE7200-K, is a two part ready-to-use kit comprising 25 mL
of Novocastra Post Primary Block, RE7111, and 25 mL of Novolink Polymer,
RE7112, sufficient to perform approximately 250 tests. The larger format
Novolink Max (Polymer), RE7260-K, is a two-part ready-to-use kit comprising
125 mL of Novocastra Post Primary Block, RE7159, and 125 mL of Novolink
Polymer, RE7161, sufficient to perform approximately 1250 tests.

Novolink Max DAB (Polymer) RE7270-K is a two part DAB kit comprising
150 mL of Novolink Substrate Buffer (Polymer), RE7163, and 8 mL of
Novocastra DAB Chromogen, RE7162, sufficient to perform approximately
1250 tests. Novolink DAB (Polymer), RE7230-K, is a two part DAB kit
comprising 30 mL of Novolink DAB Substrate Buffer, RE7143, and 3 mL
of Novocastra DAB Chromogen, RE7105, sufficient to perform
approximately 250 tests.

Novolink Polymer
FORMAT
250 Tests

CODE
RE7200-K

USAGE
P

Hematoxylin

STATUSFORMAT

IVD

25 mL

PRODUCT DESCRIPTION

1250 Tests

RE7270-K

USAGE
P

P

STATUS
IVD

Novocastra Hematoxylin, RE7107, is intended for use in immunohistochemical(IHC) staining procedures. Hematoxylin stains cell nuclei and has many uses
in histology, the most common of which is the Hematoxylin and Eosin stain.
In IHC procedures, hematoxylin can be used as a counterstain to aid thevisualization and localization of the colored end product. 25 mL of the reagent
is supplied.

Novolink Max DAB (Polymer)
CODE

RE7107USAGE

PRODUCT DESCRIPTION

Novolink (Polymer), RE7200-K, is a two part ready-to-use kit comprising 25 mL
of Novocastra Post Primary Block, RE7111, and 25 mL of Novolink Polymer,
RE7112, sufficient to perform approximately 250 tests. The larger format
Novolink Max (Polymer), RE7260-K, is a two-part ready-to-use kit comprising
125 mL of Novocastra Post Primary Block, RE7159, and 125 mL of Novolink
Polymer, RE7161, sufficient to perform approximately 1250 tests.

FORMAT

CODE

Peroxidase Detection Systems(Ready-To-Use)

STATUS
IVD

FORMAT

CODE

USAGE

STATUSPRODUCT DESCRIPTION

250 Tests

RE7110-K

P

IVD

Novolink Max DAB (Polymer) RE7270-K is a two part DAB kit comprising
150 mL of Novolink Substrate Buffer (Polymer), RE7163, and 8 mL of
Novocastra DAB Chromogen, RE7162, sufficient to perform approximately
1250 tests. Novolink DAB (Polymer), RE7230-K, is a two part DAB kit
comprising 30 mL of Novolink DAB Substrate Buffer, RE7143, and 3 mL
of Novocastra DAB Chromogen, RE7105, sufficient to perform
approximately 250 tests.

500 Tests

RE7120-K

P

IVD

PRODUCT DESCRIPTION
Novocastra Peroxidase Detection Systems (250 tests), RE7110-K, and(500 tests), RE7120-K, are for the visualization of mouse IgG, mouse IgM
and rabbit IgG primary antibodies. Each detection system contains Novocastra
Peroxidase Block, RE7101, Novocastra Protein Block, RE7102, Novocastra
Biotinylated Secondary Antibody, RE7103, Novocastra Streptavidin-HRP,
RE7104, Novocastra DAB Chromogen, RE7105, Novocastra DAB Substrate
Buffer, RE7106, and Novocastra Hematoxylin, RE7107.
The components in these kits are pre-diluted, ready-to-use reagents incolor coded bottles for ease of use and ultimate convenience.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

48

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M A N U A L

D E T E C T I O N

Streptavidin-HRP
FORMAT
25 mL

CODE
RE7104USAGE
P

STATUSIVD

PRODUCT DESCRIPTION
Streptavidin-HRP is a streptavidin-conjugated horseradish peroxidase reagent.
It is supplied ready-to-use in a volume of 25 mL.

Avidin/Biotin Blocking System
FORMAT2 x 18 mL

CODE
RE7170-K

USAGE
FPW

STATUSRUO

PRODUCT DESCRIPTION
Some tissues may bind avidin, biotinylated horseradish peroxidase, biotinylated
alkaline phosphatase or other Biotin/Avidin System components without prioraddition of biotinylated antibody. This binding may be due to endogenous biotin
or biotin-binding proteins, lectins or non-specific binding substances present in
the section. If high background is present using Avidin Biotin Complex (ABC)reagents, or other avidin conjugates in the absence of biotinylated secondary
antibody, the use of the Novocastra Avidin/Biotin Blocking System RE7170-K
may be of benefit. 18 mL of each reagent is supplied.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

49

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I H C

A D V A N C E D

S T A I N I N G–

M A N U A L

Antibody Diluent
FORMAT
500 mLD E T E C T I O N

-

I H C

Epitope Retrieval Solutions pH6
CODE
RE7133USAGE
FPO

STATUSFORMAT
1 L pH6 (x10 Concentrate)

IVD

CODE
RE7113USAGE
P (HIER)STATUSIVD

PRODUCT DESCRIPTIONPRODUCT DESCRIPTION

Novocastra IHC Diluent is intended for use as a diluent for Novocastra
primary antibodies, Novocastra Concentrated Biotinylated Secondary
Antibody, RE7108, and Novocastra Concentrated Streptavidin-HRP, RE7109,
in immunohistochemical (IHC) procedures. Novocastra IHC Diluent is notintended for the reconstitution of lyophilized reagents.

Novocastra Epitope Retrieval Solutions are intended for Heat Induced Epitope
Retrieval (HIER) on formalin-fixed, paraffin-embedded tissue sections aspart of an immunohistochemical procedure. HIER using an appropriate pH
solution improves the staining of some antibodies by exposing epitopes withintissue that has been masked during fixation. The development of Epitope
Retrieval using heat was first reported in 1991 by Shi S-R et al. , Journal of
Histochemistry and Cytochemistry 39: 741-748 (1991). Since then numerous
studies have been published looking at the effects of molarity, pH and heating
methods on epitope retrieval. A universal HIER technique suitable for all
epitopes does not exist. A combination of different heating methods andepitope retrieval solutions may be used to optimize unmasking of antigens
where this technique is recommended. HIER is not recommended for all
antibodies. Optimum conditions for epitope retrieval should be validated by
the user, as these are dependent upon tissue, fixation and/or primary antibody.
RE7113 is supplied as a 1 L volume, sufficient to prepare
10 L of working solution.

Enzyme Proteinase K (IHC)
FORMAT
100 mL

CODE

USAGE

STATUS

RE7160-K

P (Enzyme)

IVD

PRODUCT DESCRIPTION
Enzyme pretreatment of formalin-fixed, paraffin-embedded tissue sections
improves the staining of some antibodies by exposing epitopes within tissue
that have been masked during fixation. The first proteolytic enzyme employed
for epitope retrieval was trypsin. More recently, proteinase K which is commonlyused in in situ hybridization techniques has been reported to be of use.
PRODUCT SPECIFIC INFORMATION
Novocastra Enzyme Proteinase K (IHC), RE7160-K, is intended for the
enzymatic pretreatment of formalin-fixed, paraffin-embedded tissue sections
prior to incubation with a primary antibody in an immunohistochemical (IHC)
procedure. This product can be used for epitope retrieval with Novocastra
antibodies for which trypsin is recommended, known exception to this is NCLCYCLIN D1-GM. This two part kit comprises 0.75 mL of Enzyme Proteinase
K Concentrate, RE7126, and 100 mL of Enzyme Proteinase K Buffer, RE7127,
sufficient to produce 100 mL of working strength enzyme solution. This productis used in an IHC procedure, which allows the qualitative identification by lightmicroscopy. Epitope retrieval by enzymatic pretreatment is recommended for alimited number of antibodies. Optimum conditions for epitope retrieval should
be validated by the user as these are dependent upon tissue, fixation and/or
primary antibody.

Colonic adenocarcinoma pre-treated with Epitope Retrieval Solution pH6 (RE7113).
Staining for Cytokeratin 20 protein using NCL-L-CK20-561. Paraffin section.

Liver pre-treated with Enzyme Proteinase K (RE7160-K). Staining for Cytokeratin 8/18
using NCL-L-5D3. Paraffin section.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

50

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M A N U A L

D E T E C T I O N

Epitope Retrieval Solutions pH9
FORMAT
1 L pH9 (x10 Concentrate)

CODE
RE7119USAGE
P (HIER)STATUSIVD

PRODUCT DESCRIPTION
Novocastra Epitope Retrieval Solutions are intended for Heat Induced Epitope
Retrieval (HIER) on formalin-fixed, paraffin-embedded tissue sections aspart of an immunohistochemical procedure. HIER using an appropriate pH
solution improves the staining of some antibodies by exposing epitopes withintissue that has been masked during fixation. The development of Epitope
Retrieval using heat was first reported in 1991 by Shi S-R et al. Journal of
Histochemistry and Cytochemistry 39: 741-748 (1991). Since then numerous
studies have been published looking at the effects of molarity, pH and heating
methods on epitope retrieval. A universal HIER technique suitable for all
epitopes does not exist. A combination of different heating methods andepitope retrieval solutions may be used to optimize unmasking of antigens
where this technique is recommended. HIER is not recommended for all
antibodies. Optimum conditions for epitope retrieval should be validated by
the user, as these are dependent upon tissue, fixation and/or primary antibody.
RE7119 is supplied as a 1 L volume, sufficient to prepare
10 L of working solution.

Kidney pre-treated with Epitope Retrieval Solution pH9 (RE7119). Staining for Wilms’
Tumor protein using NCL-L-WT1-562. Paraffin section.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

51

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A D V A N C E D

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M A N U A L

D E T E C T I O N

-

I H C

Manual Ancillaries - Molecular
CONTENTCONCENTRATION

Whole Chromosome Buffer (WCB)

PRODUCT NAME

KBI-WCBPRODUCT CODE

10 TestRTU

CLASSIFICATION
GPR

Whole Chromosome Buffer (WCB)

KI-WCB

10 TestRTU

GPR

Tissue Digestion Kit I

KBI-60007

Kit

-

IVD

Tissue Digestion Kit I

KI-60007

Kit

-

RUO

Tissue Digestion Kit II

KBI-60004

Kit

-

IVD

Tissue Digestion Kit II

KI-60004

Kit

-

RUO

FISH Reagent Kit

KBI-60005

Kit

-

IVD

FISH Reagent Kit

KI-60005

Kit

-

RUO

FISH Digestion Kit

KBI-60006

Kit

-

IVD

FISH Digestion Kit

KI-60006

Kit

-

RUO

KREAvital Prenatal Medium (Basal)

KBI-90010

90 mL

RTU

IVD

KREAvital Prenatal Medium (Supplement)

KBI-90011

10 mL

RTU

IVD

KREAvital Prenatal Medium (Complete)

KBI-90012

100 mL

RTU

IVD

KREAvital Prenatal Medium PLUS (Complete)

KBI-90013

100 mL

RTU

IVD

KREAvital Lymphocyte Karyotyping Medium (without PHA)

KBI-90020

100 mL

RTU

IVD

KREAvital Lymphocyte Karyotyping Medium (including PHA)

KBI-90021

5 mL

RTU

IVD

KREAvital Bone Marrow Karyotyping Medium

KBI-90030

100 mL

RTU

IVD

KREAvital Myeloid Cell Medium

KBI-90031

100 mL

RTU

IVD

Colchicine Solution (10µg/ mL, in PBS)

KBI-90050

25 mL

RTU

IVD

Colcemid Solution (10µg/ mL, in PBS)

KBI-90051

10 mL

RTU

IVD

Potassium Chloride (0. 075M)

KBI-90052

100 mL

RTU

IVD

Sodium Citrate Solution (0. 8%)

KBI-90054

500 mL

RTU

IVD

Phytohaemagglutinin liquid

KBI-90056

5 mL

RTU

IVD

KREAvital Prenatal Medium (Complete)

KBI-92012

500 mL

RTU

IVD

KREAvital Lymphocyte Karyotyping Medium (without PHA)

KBI-92020

500 mL

RTU

IVD

Trypsin EDTA 10X (EDTA 0. 2%, Trypsin 0. 5%, in saline solution)

KBI-92055

100 mL

RTU

IVD

Fixogum Rubber Cement

LK-071A

125 gr-GPR

Pretreatment Solution B

LK-100C

1L

-

GPR

Wash Buffer V (10x)LK-141B

250 mL-GPR

Wash Buffer V (10x)LK-141C

1L

-

GPR

Wash Buffer II

LK-103A

100 mL-GPR

Wash Buffer I

LK-102A

100 mL-GPR

Pepsin Solution

LK-101A

2. 5 mLRTU

GPRCounterstain Diluent (antifade)

LK-097A

1 mL

-

GPR

DAPI Counterstain (1 µg/ mL)

LK-096A

1 mL

-

GPR

DAPI Counterstain (0. 1 µg/ mL)

LK-095A

1 mL

-

GPR

Paraffin Tissue Buffer (PTB)

KBI-PTB

10 TestRTU

GPR

Paraffin Tissue Buffer (PTB)

KI-PTB

10 TestRTU

GPR

FISH Hybridization Buffer (FHB)

KBI-FHB

10 TestRTU

GPR

FISH Hybridization Buffer (FHB)

KI-FHB

10 TestRTU

GPR* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

52

ANTIBODIESAKT (PHOSPHORYLATED)............................................................................................55

CD61 (GPIIIA)................................................................................................................79

ALK.................................................................................................................................55

CD68..............................................................................................................................80

ALPHA FETOPROTEIN..................................................................................................56

CD71..............................................................................................................................80

ALPHA-METHYLACYL-COA RACEMASE (AMACR, P504S)..........................................56

CD79A............................................................................................................................81

ALPHA-SYNUCLEIN.......................................................................................................57

CD79B............................................................................................................................81

ANDROGEN RECEPTOR.................................................................................................57

CD99..............................................................................................................................82

AURORA KINASE 2........................................................................................................58

CD103............................................................................................................................82

B CELL SPECIFIC OCTAMER BINDING PROTEIN-1 (BOB-1).........................................58

CD117............................................................................................................................83

BCL-2 ONCOPROTEIN...................................................................................................59

CD123............................................................................................................................83

BCL-6 ONCOPROTEIN...................................................................................................59

CD138 (SYNDECAN 1)...................................................................................................84

BETA-CATENIN..............................................................................................................60

CD141 (THROMBOMODULIN).......................................................................................84

BETA-DYSTROGLYCAN..................................................................................................60

CD146 (MCAM)..............................................................................................................85

CA125 (OVARIAN CANCER ANTIGEN)..........................................................................61

CD163............................................................................................................................85

CA19-9 (SIALYL LEWIS A)..............................................................................................61

CDX2..............................................................................................................................86

CALCITONIN..................................................................................................................62

C-ERBB-2 ONCOPROTEIN (HER-2) ANTIBODIES..........................................................86

CALPAIN ANTIBODIES..................................................................................................62

CHROMOGRANIN A.......................................................................................................87

CALPONIN (BASIC).......................................................................................................63CYCLIN D1.....................................................................................................................87

CALRETININ..................................................................................................................63CYTOKERATIN 5............................................................................................................88

CARBONIC ANHYDRASE IX...........................................................................................64CYTOKERATIN 7............................................................................................................88

CARCINOEMBRYONIC ANTIGEN (CD66E)....................................................................64CYTOKERATIN 8............................................................................................................89

CAVEOLIN-1...................................................................................................................65CYTOKERATIN 14..........................................................................................................89

CD1A..............................................................................................................................65CYTOKERATIN 17..........................................................................................................90

CD2 (LFA-2)....................................................................................................................66CYTOKERATIN 18..........................................................................................................90

CD3.................................................................................................................................66CYTOKERATIN 19..........................................................................................................91

CD4.................................................................................................................................67CYTOKERATIN 20..........................................................................................................91

CD5.................................................................................................................................67CYTOKERATIN (5/6/18).................................................................................................92

CD7.................................................................................................................................68CYTOKERATIN (8/18)....................................................................................................92

CD8.................................................................................................................................68CYTOKERATIN, MULTI (1/5/10/14) (HIGH MOLECULAR WEIGHT)..............................93

CD10..............................................................................................................................69CYTOKERATIN, MULTI (4/5/6/8/10/13/18)..................................................................93

CD11C............................................................................................................................69CYTOKERATIN, MULTI (5/6/8/18).................................................................................94

CD13..............................................................................................................................70CYTOKERATIN, MULTI (AE1/AE3).................................................................................94

CD15..............................................................................................................................70

DESMIN..........................................................................................................................95

CD16..............................................................................................................................71

DOG-1.............................................................................................................................95

CD19..............................................................................................................................71

DYSFERLIN ANTIBODIES..............................................................................................96

CD20..............................................................................................................................72

DYSTROPHIN ANTIBODIES...........................................................................................96

CD21..............................................................................................................................72

E-CADHERIN..................................................................................................................97

CD22..............................................................................................................................73

EMERIN..........................................................................................................................97

CD23..............................................................................................................................73

EPIDERMAL GROWTH FACTOR RECEPTOR.................................................................98

CD25..............................................................................................................................74

EPITHELIAL MEMBRANE ANTIGEN..............................................................................98

CD30..............................................................................................................................74

ESTROGEN RECEPTOR..................................................................................................99

CD31 (PECAM-1)...........................................................................................................75

EZH2 (ENHANCER OF ZESTE HOMOLOG 2 (DROSOPHILA)).......................................99

CD33..............................................................................................................................75

FACTOR XIIIA (BLOOD COAGULATION FACTOR XIIIA)...............................................100

CD34 (ENDOTHELIAL CELL MARKER)..........................................................................76FASCIN.........................................................................................................................100

CD38..............................................................................................................................76

FOLATE RECEPTOR ALPHA........................................................................................101

CD43..............................................................................................................................77

GALECTIN-3.................................................................................................................101

CD45..............................................................................................................................77

GASTRIN......................................................................................................................102

CD45RO..........................................................................................................................78

GEMININ......................................................................................................................102

CD56 (NCAM)................................................................................................................78

GLIAL FIBRILLARY ACIDIC PROTEIN..........................................................................103

CD57..............................................................................................................................79

GLUTATHIONE S-TRANSFERASE (GST) ANTIBODY...................................................10353

ANTIBODIESGRANZYME B...............................................................................................................104

OCT-02..........................................................................................................................128

GROSS CYSTIC DISEASE FLUID PROTEIN-15.............................................................104

OCT-3/4........................................................................................................................129

HELICOBACTER PYLORI..............................................................................................105

P16...............................................................................................................................129

HUMAN CHORIONIC GONADOTROPHIN (BETA).......................................................105

P21 (WAF1 PROTEIN)..................................................................................................130

HUMAN FOLLICLE STIMULATING HORMONE (BETA 2) (HFSH)...............................106

P53 PROTEIN...............................................................................................................130

HUMAN GROWTH HORMONE (HGH)..........................................................................106

P53 PROTEIN (CM5)....................................................................................................131

HUMAN HERPESVIRUS 8 (HHV8)...............................................................................107

P57 PROTEIN (KIP2)....................................................................................................131

IMMUNOGLOBULIN A..................................................................................................107

P63 PROTEIN...............................................................................................................132

IMMUNOGLOBULIN D..................................................................................................108

P120 CATENIN.............................................................................................................132

IMMUNOGLOBULIN G.................................................................................................108

PARATHYROID HORMONE (PTH)................................................................................133

IMMUNOGLOBULIN M.................................................................................................109

PAX-5............................................................................................................................133

INHIBIN ALPHA...........................................................................................................109

PD-L1............................................................................................................................134

INSULIN.......................................................................................................................110

PERFORIN....................................................................................................................134

INTERLEUKIN 6............................................................................................................110

PLACENTAL ALKALINE PHOSPHATASE....................................................................135

KAPPA LIGHT CHAIN..................................................................................................111

POLO-LIKE KINASE 1 (PLK-1)......................................................................................135

KI67 ANTIGEN.............................................................................................................111

PROGESTERONE RECEPTOR......................................................................................136

LAMBDA LIGHT CHAIN...............................................................................................112

PROGESTERONE RECEPTOR (A/B FORMS)................................................................136

LANGERIN....................................................................................................................112

PROSTATE SPECIFIC ANTIGEN..................................................................................137

LYSOZYME (MURAMIDASE)........................................................................................113

PROSTATE SPECIFIC MEMBRANE ANTIGEN.............................................................137

MAMMAGLOBIN..........................................................................................................113

PROSTATIC ACID PHOSPHATASE..............................................................................138

MAST CELL TRYPTASE...............................................................................................114

PROTEIN GENE PRODUCT 9.5....................................................................................138

MELAN A......................................................................................................................114

RETINOBLASTOMA GENE PROTEIN...........................................................................139

MELANOMA MARKER (HMB45).................................................................................115

S-100............................................................................................................................139

MEROSIN LAMININ ALPHA 2 CHAIN.........................................................................115

SARCOGLYCAN ANTIBODIES......................................................................................140

MESOTHELIN...............................................................................................................116

SEROTONIN.................................................................................................................140

MICROPHTHALMIA TRANSCRIPTION FACTOR (MITF).............................................116

SMA (ALPHA SMOOTH MUSCLE ACTIN)...................................................................141

MISMATCH REPAIR PROTEIN (MLH1)........................................................................117

SPECTRIN....................................................................................................................141

MISMATCH REPAIR PROTEIN (MSH2)........................................................................117

SURFACTANT PROTEIN A...........................................................................................142

MISMATCH REPAIR PROTEIN (MSH6)........................................................................118

SYNAPTOPHYSIN........................................................................................................142

MISMATCH REPAIR PROTEIN (PMS2)........................................................................118

TARTRATE-RESISTANT ACID PHOSPHATASE (TRAP)...............................................143

MUC-1 GLYCOPROTEIN...............................................................................................119

TERMINAL DEOXYNUCLEOTIDYL TRANSFERASE.....................................................143

MUC-2 GLYCOPROTEIN...............................................................................................119

THYROGLOBULIN........................................................................................................144

MUC-5AC GLYCOPROTEIN..........................................................................................120

THYROID PEROXIDASE...............................................................................................144

MUC-6 GLYCOPROTEIN...............................................................................................120

THYROID STIMULATING HORMONE..........................................................................145

MULTIPLE MYELOMA ONCOGENE 1 (MUM-1)...........................................................121

THYROID TRANSCRIPTION FACTOR-1.......................................................................145

MUSCLE SPECIFIC ACTIN...........................................................................................121

TOPOISOMERASE I......................................................................................................146

MYELOPEROXIDASE....................................................................................................122

TOPOISOMERASE II ALPHA........................................................................................146

MYOD1 (RHABDOMYOSARCOMA MARKER)..............................................................122

TYROSINASE...............................................................................................................147

MYOGENIN (MYF-4).....................................................................................................123

TYROSINE HYDROXYLASE..........................................................................................147

MYOGLOBIN.................................................................................................................123

UTROPHIN...................................................................................................................148

MYOSIN HEAVY CHAIN ANTIBODIES.........................................................................124

VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-3.....................................148

MYOTILIN.....................................................................................................................124

VILLIN..........................................................................................................................149

NAPSIN A.....................................................................................................................125

VIMENTIN....................................................................................................................149

N-CADHERIN................................................................................................................125

VON WILLEBRAND FACTOR (FACTOR VIII-RELATED ANTIGEN)................................150

NEGATIVE CONTROL (MOUSE)...................................................................................126

WILMS’ TUMOR............................................................................................................150

NEGATIVE CONTROL (RABBIT)...................................................................................126

ZAP-70.........................................................................................................................151

NEUROFILAMENT 200KD............................................................................................127

CELL MARQUE.............................................................................................................152

NEURON SPECIFIC ENOLASE.....................................................................................127
NITRIC OXIDE SYNTHASE 1........................................................................................128

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Akt (Phosphorylated)

ALK

Human skin: immunohistochemical staining for Phosphorylated Akt.
Akt (Phosphorylated): clone LP18

Non-small cell lung cancer: immunohistochemical staining for ALK. ALK: clone 5A4

E

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5A4

LP18
FORMAT

CODE

USAGE

US

EU

ROW*

Liquid 1 mL

NCL-L-Akt-Phos

P(HIER)

IVD

IVD

IVD

FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0831

P(HIER)

IVD

IVD

IVD

EU

ROW*

PATHOLOGY MENUPATHOLOGY MENULUNG PATHOLOGY

SPECIALIZED

5A4

ANTIGEN BACKGROUND
Akt-1, also referred to as protein kinase B (PKB) or Rac alpha is a memberof the Akt serin/threonine protein kinase family. It plays an important role inmany biological responses including metabolism, cell survival and growth byphosphorylation and inactivating several targets including GSK 3 beta, caspase 9,
BAD and the forkhead transcription factor.

FORMAT

CODE

USAGE

US

BOND 7 mL

PA0306P(HIER)

IVD

IVD

IVD

Liquid 0.5 mL

NCL-L-ALK

P(HIER)

IVD

IVD/RUO

IVD/RUOPATHOLOGY MENUHEMATOPATHOLOGY

Akt (Phosphorylated) is recommended for the detection of specific antigens
of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

ANTIGEN BACKGROUNDPRODUCT SPECIFIC INFORMATION

Anaplastic large cell lymphoma (ALCL) is usually composed of large pleomorphic
cells which are reported to express CD30 antigen and epithelial membrane
antigen (EMA). These tumor cells tend to occur in younger individuals and may
be associated with cutaneous and extranodal involvement. A proportion ofthese cases contain a chromosomal translocation t(2;5) (p23;q35). This results
in a hybrid gene encoding part of the nucleophosmin (NPM) gene joined to thecytoplasmic domain of the anaplastic lymphoma kinase (ALK) gene, giving rise to
the protein, p80. Large cell lymphomas account for approximately 25% of all nonHodgkin’s lymphomas in children and young adults, of which one third carry the
NPM-ALK gene translocation.

Akt-Phos is not recommended for use with PBS, since the use of PBS-based wash
buffers and possibly PBS-based antibody diluents gives increased backgroundstaining and decreased staining intensity. Proprietary reagents from Leica
Biosystems or TBS-based wash buffer and diluents are recommended.

ALK is recommended for the detection of specific antigens of interest in normal
and neoplastic tissues, as an adjunct to conventional histopathology using nonimmunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Alpha Fetoprotein

Alpha-Methylacyl-CoA Racemase(AMACR, p504s)

Human fetal liver: immunohistochemical staining for Alpha Fetoprotein.
Alpha Fetoprotein: clone C3

Human prostatic adenocarcinoma: immunohistochemical staining for AMACR.
AMACR: clone EPMU1

C3

EPMU1

I

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CODE

USAGE

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EU

ROW*

FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0963

P

IVD

IVD

IVD

BOND 7 mL

PA0210P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-AFP

P

IVD

IVD

IVD

Liquid 1 mL

NCL-L-AMACR

P(HIER)

IVD

IVD

IVD

S

PATHOLOGY MENUPATHOLOGY MENUGYNEPATHOLOGYUROPATHOLOGYANTIGEN BACKGROUNDANTIGEN BACKGROUND

Alpha fetoprotein (AFP) is an oncofetal antigen of 70 kD found in body fluids,
which if detected in high concentrations has clinical implications.

Alpha-methylacyl-CoA racemase (AMACR), also known as p504s, is a
mitochondrial and peroxisomal enzyme that is involved in bile acid biosynthesis
and beta-oxidation of branched-chain fatty acids. AMACR is essential in lipid
metabolism, and is expressed in normal liver (hepatocytes), kidney (tubularepithelial cells) and gall bladder (epithelial cells). Expression has also beenfound in lung (bronchial epithelial cells) and colon (colonic surface epithelium).
Expression is granular and cytoplasmic. AMACR expression can also be found inhepatocellular carcinoma and kidney carcinoma. Past studies have also shownthat AMACR is expressed in various colon carcinomas (well, moderately and poorly
differentiated) and over expressed in prostate carcinoma.

AFP is expressed in fetal liver but is not present under normal circumstances inhealthy adult tissues. It is reported to be expressed in a proportion of germ celltumors, with high frequency in yolk sac tumors.
Alpha Fetoprotein is recommended for the detection of specific antigens of interestin normal and neoplastic tissues, as an adjunct to conventional histopathology
using non-immunologic histochemical stains.

Alpha-Methylacyl-CoA Racemase (AMACR, p504s) is recommended for thedetection of specific antigens of interest in normal and neoplastic tissues, as an
adjunct to conventional histopathology using non-immunologic histochemical
stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Alpha-Synuclein

Androgen Receptor

Human brain, Lewy body dementia: immunohistochemical staining for alpha-synuclein. Notestaining of alpha-synuclein-containing Lewy bodies. Alpha-Synuclein: clone KM51

Human skin: immunohistochemical staining for Androgen Receptor. Note the nuclear stainingof the epithelial cells. Androgen Receptor: clone AR27

KM51

AR27

FORMAT

CODE

USAGE

US

EU

ROW*

FORMAT

CODE

USAGE

US

EU

ROW*

Liquid 1 mL

NCL-L-ASYN

P(HIER)

RUO

RUO

RUO

Liquid 1 mL

NCL-L-AR-318

P(HIER)

IVD

IVD

IVD

PATHOLOGY MENUPATHOLOGY MENUNEUROPATHOLOGYUROPATHOLOGYANTIGEN BACKGROUNDANTIGEN BACKGROUND

Alpha-synuclein is a protein of 140 amino acids and a member of the synuclein
family. It shares 61% sequence homology with beta-synuclein and is highly
conserved between vertebrate species. It does not possess a signal sequencesuggesting that it is an intracellular protein. All synucleins have an unusualorganization based around the eleven residue repeating motif and an alphahelical secondary structure resembling those found in the lipid-binding domain of
exchangeable apolipoproteins, including Apo E. This homology suggests a directinteraction of alpha-synuclein with membranes consistent with its affinity forsynaptosomes.

Androgen receptor is a member of the superfamily of ligand responsive
transcription regulators. The androgen receptor functions in the nucleus where it
is believed to act as a transcriptional regulator mediating the action of male sex
hormones (androgens). The androgen receptor has wide distribution and can bedemonstrated by immunohistochemistry in several tissues e.g. prostate, skin,and oral mucosa. Androgen receptor has been reported in a diverse range ofhuman tumors eg osteosarcoma, and in prostatic carcinoma androgen receptor
expression may be of clinical relevance. Furthermore, mutation of the geneencoding androgen receptor has been reported in prostatic carcinoma.

The function of alpha-synuclein may be to carry a target protein to the inner
membrane of nerve terminals or to the outer surface of synaptic vesicles. Western
Blot analyses of highly purified Lewy bodies from Lewy body dementia brain
material has shown full-length, partially truncated and insoluble aggregates ofalpha-synuclein.

Androgen Receptor is recommended for the detection of specific antigens
of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

Alpha-synuclein may be implicated in the formation of Lewy bodies and theselective degeneration of neurons in sporadic Parkinson’s disease and Lewy bodydementia.
PRODUCT SPECIFIC INFORMATION
Clone KM51 is specific for alpha-synuclein and is unreactive with beta-synuclein.
Pretreatment of tissue sections with 98-100% formic acid is also recommended.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Aurora Kinase 2

B Cell Specific Octamer Binding Protein-1(BOB-1)

HeLa cell line: immunohistochemical staining for Aurora Kinase. Note nuclear staining of a
proportion of cells. Aurora Kinase 2: clone JLM28

Human tonsil: Immunohistochemical staining for BOB-1. Note nuclear and cytoplasmic
staining of B cells with BOB-1: clone TG14

JLM28

TG14

FORMAT

CODE

Liquid 1 mL

NCL-L-AK2

USAGE
-

US

EU

ROW*

FORMAT

CODE

USAGE

ASR

RUO

RUO

BOND 7 mL

PA0558P(HIER)

Liquid 1 mL

NCL-L-BOB-1

PATHOLOGY MENUSPECIALIZED

US
-

EU

ROW*

IVD

IVD

IVD

ASR

RUO

RUO

PATHOLOGY MENUHEMATOPATHOLOGYANALYTE SPECIFIC REAGENTANALYTE SPECIFIC REAGENT

Analyte Specific Reagent. Analytical and performance characteristics are notestablished.

Analyte Specific Reagent. Analytical and performance characteristics are notestablished.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Bcl-2 Oncoprotein

Bcl-6 Oncoprotein

Human follicular lymphoma: immunohistochemical staining for Bcl-2. Bcl-2: clone bcl-2/100/
D5

Human diffuse large B cell lymphoma: immunohistochemical staining for Bcl-6. Bcl-6: clone
LN22

bcl-2/100/D5

LN22

FORMAT

CODE

USAGE

US

EU

ROW*

FORMAT

CODE

BOND 7 mL

PA0117P(HIER)

IVD

IVD

IVD

BOND 7 mL

Liquid 1 mL

NCL-L-bcl-2

P(HIER)

IVD

IVD

IVD/RUO

Liquid 1 mL

USAGE

US

EU

ROW*

PA0204P(HIER)

IVD

IVD

IVD

NCL-L-Bcl-6-564

P(HIER)

IVD

IVD

IVD/RUOPATHOLOGY MENUPATHOLOGY MENUHEMATOPATHOLOGYHEMATOPATHOLOGYANTIGEN BACKGROUNDANTIGEN BACKGROUND

Bcl-2 is a member of a family of proteins that are involved in apoptosis. Bcl-2 isan integral inner mitochondrial membrane protein of 25 kD and has a wide tissue
distribution. It is considered to act as an inhibitor of apoptosis. For this reason,bcl-2 expression is inhibited in germinal centers where apoptosis forms part of the
B cell production pathway.

Bcl-6 is a proto-oncogene that encodes a Kruppel-type zinc-finger protein of 95
kD and shares homology with other transcription factors. Bcl-6 protein is mainly
expressed in normal germinal center B cells and related lymphomas. It has beenshown that the Bcl-6 proto-oncogene is involved in chromosome rearrangements
at 3q27 in non-Hodgkin’s lymphomas and Bcl-6 rearrangements have also been
detected in 33-45% of diffuse large B cell lymphomas. Immunohistochemistry
has been reported to show the Bcl-6 gene product to be detectable in follicularlymphomas, diffuse large B cell lymphomas, Burkitt’s lymphomas and in nodular,
lymphocyte predominant Hodgkin’s disease.

In 90% of follicular lymphomas a translocation occurs which juxtaposes thebcl-2 gene at 18q21, to an immunoglobulin gene. This t(14;18) translocation
can deregulate gene expression and bcl-2 over-expression can be demonstrated
immunohistochemically in the vast majority of follicular lymphomas.

Bcl-6 Oncoprotein is recommended for the detection of specific antigens
of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

Bcl-2 Oncoprotein is recommended for the detection of specific antigens
of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Beta-Catenin

Beta-Dystroglycan

Human colon polyp: immunohistochemical staining for Beta-Catenin. Note the abnormaltranslocation of the protein to the nucleus. Beta-Catenin: clone 17C2

Human skeletal muscle: immunohistochemical staining on a frozen longitudinal section.
Staining is localized in the sarcolemma of the fibers. Beta-Dystroglycan: clone 43DAG1/8D5

17C2

43DAG1/8D5FORMAT

CODE

USAGE

US

EU

ROW*

FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0083P(HIER)

IVD

IVD

IVD

Lyophilized 1 mL

NCL-b-DG

F

IVD

IVD

IVD

Liquid 1 mL

NCL-L-B-CAT

P(HIER)

IVD

IVD

IVD

PATHOLOGY MENUPATHOLOGY MENUMUSCLE PATHOLOGYSOFT TISSUE PATHOLOGYANTIGEN BACKGROUNDANTIGEN BACKGROUND

Dystrophin associated glycoproteins (DAGs) are involved in the attachment ofdystrophin to muscle membranes. The biological significance of this dystrophin/glycoprotein complex is not fully understood, but it appears to form an essential
linkage between actin on the inside of the muscle fiber and muscle laminin in thebasal lamina which surrounds the fiber. Beta-dystroglycan spans the sarcolemma
and it has been suggested that it is the member of the complex which binds
directly to dystrophin.

The catenins, (alpha, beta and gamma) are cytoplasmic proteins which bind tothe highly conserved tail of the E-cadherin molecule. Beta-catenin is a componentof the adherens junction, a multiprotein complex which supports Ca2+ -dependentcell-to-cell contact, which in itself is critical for adhesion, signal transmission
and for anchoring the actin cytoskeleton. Beta-catenin’s role is as a transcription
effector of the wnt-signaling pathway. Immunohistochemistry is the best way
to demonstrate nuclear expression of beta-catenin and wnt-pathway activation.
This aberrant expression is observed in human tumorigenesis, and especially incolorectal cancer.

Beta-Dystroglycan is recommended for the detection of specific antigens
of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

Beta-Catenin is recommended for the detection of specific antigens of interest in
normal and neoplastic tissues, as an adjunct to conventional histopathology using
non-immunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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CA125 (Ovarian Cancer Antigen)CA19-9 (Sialyl Lewis a)

Human adenocarcinoma of endometrium: immunohistochemical staining on CA125.
CA125: clone Ov185:1

Colonic adenocarcinoma: immunohistochemical staining for Sialyl Lewis a antigen.
CA19-9: clone C241:5:1:4

Ov185:1

C241:5:1:4
US

EU

E

FORMAT

CODE

USAGE

US

EU

ROW*

FORMAT

CODE

USAGE

BOND 7 mL

PA0539P(HIER)

IVD

IVD

IVD

BOND 7 mL

PA0424P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-CA125

P(HIER)

IVD

IVD

IVD/RUO

Liquid 1 mL

NCL-L-CA19-9

P(HIER)

RUO

RUO

RUO

S

ROW*

PATHOLOGY MENUPATHOLOGY MENUGYNEPATHOLOGYGASTROINTESTINAL PATHOLOGYANTIGEN BACKGROUNDANTIGEN BACKGROUND

CA125 antigen is usually associated with ovarian epithelial malignancies. Serum
assays are widely used to detect this protein in the monitoring of ovarian cancers.
CA125 antigen may also be detected by immunohistochemistry and expression
has been found in neoplasms such as seminal vesicle carcinoma and anaplastic
lymphoma. CA125 antigen is not found exclusively in malignant tumors. CA125 isalso known as MUC16.

CA19-9 is an epitope on the sialylated Lewisa carbohydrate structure. Sialylated
Lewisa plays a role in cell adhesion by acting as a functional ligand for the
inducible adhesion molecule E-selectin. In carcinoma of the pancreas, it is reported
that the immunohistochemical expression of both CA19-9 and CA50 correlateswith tumor differentiation, where the strongest staining is observed in welldifferentiated tumors. These two markers are also reported in a number of benign
lesions such as chronic pancreatitis.

CA125 (Ovarian Cancer Antigen) is recommended for the detection of specificantigens of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

CA19-9 (Sialyl Lewis a) is recommended for the detection of specific antigens
of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.
PRODUCT SPECIFIC INFORMATION
Clone C241:5:1:4 reacts specifically with Sialyl Lewis a - containing glycolipids,
showing no crossreaction with Lewis a, Lewis b, or other structurally related
molecules. The epitope recognized by NCL-L-CA19-9 is designated CA19-9.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Calcitonin

Calpain Antibodies

Human medullary thyroid carcinoma: immunohistochemical staining for Calcitonin.
Calcitonin: clone CL1948

Western Blot: analysis of human skeletal muscle showing detection of calpain 3 proteins.
Lane A, calpain 3 bands at 94 and 30 kD detected with CALP-2C4. Lane B, Calpain 3 bands
at 94 and approximately 60 kD detected with CALP-12A2. Calpain: clone Calc3d/2C4
Calpain: clone Calp3c/12A2

CL1948
FORMAT

CODE

USAGE

US

EU

ROW*

Calp3c/12A2

Liquid 1 mL

NCL-L-CALCITONIN

P(ENZYME)

IVD

IVD

IVD

FORMAT

CODE

USAGE

US

EU

ROW*

Lyophilized 2.5 mL

NCL-CALP-12A2

W

RUO

RUO

RUO

Polyclonal
FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0406P(ENZYME)

IVD

IVD

IVD

S

Calp3d/2C4

PATHOLOGY MENU
HEAD, NECK AND ENDOCRINEFORMAT

CODE

USAGE

US

EU

ROW*

Lyophilized 2.5 mL

NCL-CALP-2C4

W

RUO

RUO

RUO

PATHOLOGY MENUMUSCLE PATHOLOGYANTIGEN BACKGROUND
Calcitonin (CT) is a 32 amino acid peptide synthesized by the parafollicular C
cells of the thyroid. It acts through its receptors to inhibit osteoclast mediatedbone resorption, decrease calcium resorption by the kidney and decrease calcium
absorption by the intestines. The action of calcitonin is therefore to cause areduction in serum calcium, an effect opposite to that of parathyroid hormone. The
calcitonin gene transcript also encodes the calcitonin gene-related peptide (CGRP),
which is thought to be a potent vasodilator. The tissue specificity of the transcript
produced depends on alternative splicing of the CT/CGRP gene transcript. In theparafollicular cells of the thyroid 95% of the CT/CGRP is processed and translated
to produce CT, however, in neuronal cells 99% of the CT/CGRP RNA is translated
into CGRP. The C cells of the thyroid give rise to an endocrine tumor, medullary
thyroid carcinoma (MTC), which occurs in a sporadic (75% of cases) and hereditary
form (25% of cases). Familial MTC is associated with C cell hyperplasia (CCH),
whereas sporadic MTC is thought not to be. However, in the general population
CCH is present in 20-30% of thyroid glands, either with normal histology, thyroiditis
or follicular tumors.

ANTIGEN BACKGROUND
The gene responsible for LGMD2A has been identified as the chromosome 15q15encoded muscle-specific calcium-activated neutral protease, calpain 3. Calpain
3 enzyme is only stable in human muscle when homogenized in treatment buffer
immediately after harvest (Anderson LVB et al. Am. J. of Pathol. 153(4), 1169-1179(1998)), and in homogenates containing SDS and is therefore well suited foranalysis by Western Blot. CALP-2C4 reacts with the full-size calpain 3 (94kD) andan additional fragment (30kD) in human skeletal muscle. CALP-12A2 reacts withfull-size protein plus apparent degradation products at approximately 60kD.

Calcitonin is recommended for the detection of specific antigens of interest in
normal and neoplastic tissues, as an adjunct to conventional histopathology using
non-immunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Calponin (Basic)

Calretinin

Human prostate: immunohistochemical staining for Calponin (Basic). Note staining of basal
cells. Calponin (Basic): clone 26A11

Human small cell lung carcinoma: immunohistochemical staining for Calretinin.
Calretinin: clone CAL6

26A11

CAL6

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FORMAT

CODE

USAGE

US

EU

ROW*

FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0416P(HIER)

IVD

IVD

IVD

BOND 7 mL

PA0346P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-CALRET-566

P(HIER)

IVD

IVD

IVD

PATHOLOGY MENUMUSCLE PATHOLOGYSPATHOLOGY MENULUNG PATHOLOGYANTIGEN BACKGROUNDANTIGEN BACKGROUND

Basic calponin (calponin-h1) is a 34 kD protein which exhibits a high degreeof homology to acidic and neutral calponins at its N-terminal region. It is an
actin, tropomyosin and calmodulin binding protein thought to be involved in
the regulation of smooth muscle contraction. The expression of basic calponinis reported to be restricted to smooth muscle cells and is a marker of thedifferentiated contractile phenotype of developing smooth muscle. Vascularsmooth muscle cells convert to a synthetic dedifferentiated phenotype when thisprotein is lost and this is a key stage in both atherosclerosis and restenosis ofcoronary arteries after balloon angioplasty. It is thought that basic calponin exerts
its effect via the cortical actin cytoskeleton, and therefore influences proliferation,
the transformed phenotype and the metastatic potential of tumor cells. Basic
calponin mRNA is expressed in smooth muscle of prostate, bowel and aorta,
whereas neutral and acidic calponin mRNAs are expressed in non-smooth muscle
tissues such as heart, placenta, lung, kidney, pancreas, spleen, testis and ovary as
well as in smooth muscle-containing tissues.

Calretinin is a calcium-binding protein of 29 kD that is a member of the family of
so-called EF-hand proteins that also includes S-100 proteins. Calretinin is reported
to be abundantly expressed in neurons. Outside the nervous system, calretinin
is reported to be expressed in a range of cell types including mesothelial cells,
steroid producing cells, (for example adrenal cortical cells, Leydig cells, ovarian
theca interna cells, Sertoli cells, some neuroendocrine cells, eccrine sweat glands)
and other cell types.
Calretinin is recommended for the detection of specific antigens of interest in
normal and neoplastic tissues, as an adjunct to conventional histopathology using
non-immunologic histochemical stains.

Calponin (Basic) is recommended for the detection of specific antigens of interestin normal and neoplastic tissues, as an adjunct to conventional histopathology
using non-immunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Carbonic Anhydrase IX

Carcinoembryonic Antigen (CD66e)

Human stomach: immunohistochemical staining for Carbonic Anhydrase IX. Note intense
membrane and cytoplasmic staining of the deep glands. Carbonic Anhydrase IX: clone TH22

Human bowel: immunohistochemical staining for CD66e. Note cytoplasmic staining ofepithelial cells. CD66e: clone 12-140-10

TH22

COL-1

FORMAT

CODE

USAGE

US

EU

ROW*

FORMAT

CODE

USAGE

US

EU

ROW*

Liquid 1 mL

NCL-L-CAIX

P(HIER)

IVD

IVD

IVD

BOND 7 mL

PA0848P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-CEA-609

P(HIER)

IVD

IVD

IVD

PATHOLOGY MENU
UROPATHOLOGYSPATHOLOGY MENUGASTROINTESTINAL PATHOLOGYANTIGEN BACKGROUNDANTIGEN BACKGROUND

Carbonic anhydrase (CA) is an enzyme that assists rapid interconversion of carbon
dioxide and water into carbonic acid, protons, and bicarbonate ions. Originallynamed MN/G250, carbonic anhydrase IX (CAIX) is a cell surface transmembraneprotein, which is predominantly found in the gastrointestinal tract and gallbladder.
The glandular regions of normal colon are reported to be negative, but in the caseof adenocarcinoma, the glands are positive. CAIX is also reported to be expressedin common epithelial tumors such as carcinomas of the esophagus, lung, colon,
kidney, cervix and non-small cell lung carcinoma.In breast carcinomas, CAIX
expression has been reported to be associated with malignant tissue. Expressionof CAIX is reported to be absent in normal kidney, chromophobe carcinomas or
oncocytomas; however, it is specifically expressed in clear cell renal carcinomas.

Carcinoembryonic antigen (CEA) is a heterogeneous cell surface glycoprotein
produced by cells of fetal colon. Low levels are also found on normal mucosal
epithelia of the adult colon and a variety of other normal tissues. CEA is encodedby the CEA gene, which is located on chromosome 19. It is a member of the CEA
gene family, which in turn is a subfamily of the immunoglobulin superfamily.
Cell adhesion properties are now well recognized for CEA. It is believed thatthe expression of this glycoprotein in conjunction with other known adhesion
molecules will influence the cell-cell interaction.
Carcinoembryonic Antigen (CD66e) is recommended for the detection of specificantigens of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

Carbonic Anhydrase IX is recommended for the detection of specific antigens
of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Caveolin-1

CD1aNormal human colon: immunohistochemical staining for Caveolin-1. Note cytoplasmic stainingof smooth muscle and endothelium. Caveolin-1: clone 4D6

Human thymoma: immunohistochemical staining for CD1a. CD1a: clone MTB1

CODE

USAGE

US

EU

ROW*

Liquid 1 mL

NCL-L-Caveolin-1

P(HIER)

RUO

RUO

RUO

E

S

MTB1

4D6
FORMATI

PATHOLOGY MENUSPECIALIZEDFORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0235P(HIER)

IVD

IVD

IVD

Liquid 0.5 mL

NCL-L-CD1a-235

P(HIER)

IVD

IVD

IVD/RUO

Liquid 1 mL

NCL-L-CD1a-235

P(HIER)

IVD

IVD

IVD

PATHOLOGY MENU
DERMATOPATHOLOGYANTIGEN BACKGROUND
Caveolin-1 is a major structural component of caveolae, which are vesicularinvaginations present on the plasma membrane of different cell types. It plays aregulatory role in several signaling pathways and is reported to be most abundantly
expressed in terminally differentiated mesenchymal cells such as smooth muscle
cells, adipocytes and endothelial cells. High levels are also reported in fibroblasts
where a fine granular membranous and diffuse cytoplasmic staining pattern is
described.

ANTIGEN BACKGROUND
CD1a is a protein of 43 to 49 kD expressed on dendritic cells and cortical
thymocytes. CD1a antigen expression has been shown to be useful indifferentiating Langerhans cells, powerful antigen presenting cells present in skinand epithelia, from interdigitating cells. Immunohistochemical studies for CD1aantigen have reported a reduction in epidermal Langerhans cells in graft versus
host disease and the participation of CD1a antigen-positive dendritic cells in
atherosclerotic lesion formation and asthmatic inflammation.
CD1a is recommended for the detection of specific antigens of interest in normal
and neoplastic tissues, as an adjunct to conventional histopathology using nonimmunologic histochemical stains.
PRODUCT SPECIFIC INFORMATION
Clone MTB1 detects cortical thymocytes, Langerhans cells in epidermis,
interdigitating cells of dermis and interdigitating cells of stratified squamous
epithelium of tonsil. Clone MTB1 may also detect small focal groups oflymphocytes outside the germinal centers of tonsil indicating a cross-reaction with
CD1b antigen.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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CD2 (LFA-2)

CD3

Human tonsil: immunohistochemical staining for CD2. Note membrane staining of T
lymphocytes. CD2: clone 11F11

Human skin with mycosis fungoides: immunohistochemical staining for CD3. Note theextensively infiltrated positive cells. CD3: clone LN10

11F11

LN10

FORMAT

CODE

USAGE

US

EU

ROW*

FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0271

P(HIER)

IVD

IVD

IVD

BOND 7 mL

PA0553P(HIER)

IVD

IVD

IVD

BOND 30 mL

PA0122P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-CD3-565

P(HIER)

IVD

IVD

IVD

AB75
FORMAT

CODE

USAGE

US

EU

ROW*

Liquid 1 mL

NCL-L-CD2-271

P(HIER)

IVD

IVD

IVD/RUOPATHOLOGY MENUHEMATOPATHOLOGYPATHOLOGY MENUANTIGEN BACKGROUNDHEMATOPATHOLOGYThe CD3 molecule consists of five different polypeptide chains with molecularweights ranging from 16 to 28 kD. The CD3 antigen is first detected in early
thymocytes and its appearance probably represents one of the earliest signs ofcommitment to the T cell lineage.

ANTIGEN BACKGROUNDThe CD2 antigen (LFA-2) is a monomeric 45 to 58 kD glycoprotein. It is anaccessory molecule important in mediating the adhesion of activated T cells andthymocytes with antigen-presenting cells and target cells.

CD3 is recommended for the detection of specific antigens of interest in normal
and neoplastic tissues, as an adjunct to conventional histopathology using nonimmunologic histochemical stains.

CD2 (LFA-2) is recommended for the detection of specific antigens of interest in
normal and neoplastic tissues, as an adjunct to conventional histopathology using
non-immunologic histochemical stains.

PRODUCT SPECIFIC INFORMATION
Clone LN10 is specific for the non-glycosylated epsilon chain of the human CD3
molecule. Clone LN10 recognizes T cells in thymus, bone marrow, peripheral
lymphoid tissue and blood and is a pan T cell marker.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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CD4

CD5

T-Cell Lymphoma: immunohistochemical staining of CD4. CD4: clone 4B12

Human mantle cell lymphoma: immunohistochemical staining for CD5. CD5: clone 4C7

4B12

4C7

S

FORMAT

CODE

USAGE

US

EU

ROW*

FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0427P(HIER)

IVD

IVD

IVD

BOND 7 mL

PA0168P(HIER)

IVD

IVD

IVD

Liquid 0.5 mL

NCL-L-CD4-368

P(HIER)

IVD

IVD

IVD/RUO

Liquid 0.5 mL

NCL-L-CD5-4C7

P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-CD4-368

P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-CD5-4C7

P(HIER)

IVD

IVD/RUO

IVD/RUOPATHOLOGY MENUPATHOLOGY MENUHEMATOPATHOLOGYHEMATOPATHOLOGYANTIGEN BACKGROUNDANTIGEN BACKGROUNDThe CD4 molecule (T4) is a single chain transmembrane glycoprotein with amolecular weight of 59 kD. The CD4 antigen is expressed on a T cell subset(helper/inducer) representing 45% of peripheral blood lymphocytes and at a lower
level on monocytes and germinal center macrophages. Most cases of cutaneous T
cell lymphoma, including mycosis fungoides, express the CD4 antigen and HTLV-1
associated adult T cell leukemia/lymphoma is also generally CD4 positive.

CD5 antigen is reported to be expressed on 95% of thymocytes and 72% of
peripheral blood lymphocytes. In lymph nodes, the main reactivity is observed
on T cells. CD5 antigen is also expressed by many T cell leukemias, lymphomas,
activated T cells and on a subset of B cells located primarily in the mantle zones
of normal lymph nodes. CD5 antigen expression is also reported in T cell acutelymphocytic leukemias (T-ALL), some B cell chronic lymphocytic leukemias (B-CLL)
as well as B and T cell lymphomas.

CD4 is recommended for the detection of specific antigens of interest in normal
and neoplastic tissues, as an adjunct to conventional histopathology using nonimmunologic histochemical stains.

CD5 is recommended for the detection of specific antigens of interest in normal
and neoplastic tissues, as an adjunct to conventional histopathology using nonimmunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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CD7

CD8

T cell lymphoma: immunohistochemical staining for CD7. CD7: clone LP15

Human lymph node, T cell lymphoma: immunohistochemical staining for CD8.
CD8: clone 4B11

LP15
FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0266P(HIER)

IVD

IVD

IVD

NCL-L-CD7-580

P(HIER)

IVD

IVD

IVD

Liquid 1 mL

I

E

S

4B11

PATHOLOGY MENUHEMATOPATHOLOGYFORMAT

CODE

USAGE

US

EU

BOND 7 mL

ROW*

PA0183P(HIER)

IVD

IVD

IVD

Liquid 0.5 mL

NCL-L-CD8-4B11

P(HIER)

IVD

IVD

IVD/RUO

Liquid 1 mL

NCL-L-CD8-4B11

P(HIER)

IVD

IVD

IVD/RUOPATHOLOGY MENUHEMATOPATHOLOGYANTIGEN BACKGROUNDThe CD7 molecule is a membrane-bound glycoprotein of 40 kD and is the earliest T
cell specific antigen to be expressed in lymphocytes. CD7 antigen is also the only
early marker to persist throughout differentiation. The function and role of the CD7
molecule has not yet been fully identified, although the activation of T cells withgamma/delta receptors has been proposed based on mAb-induced activation. CD7
antigen is reported to be found on the majority of peripheral blood T cells, mostnatural killer cells and thymocytes.

ANTIGEN BACKGROUNDThe CD8 molecule is composed of two chains and has a molecular weight of
32 kD. It is found on a T cell subset of normal cytotoxic/suppressor cells whichmake up approximately 20-35% of human peripheral blood lymphocytes.The CD8
antigen is reported to be detected on natural killer cells, 80% of thymocytes, on a
subpopulation of 30% of peripheral blood null cells and 15-30% of bone marrowcells.

CD7 is recommended for the detection of specific antigens of interest in normal
and neoplastic tissues, as an adjunct to conventional histopathology using nonimmunologic histochemical stains.

CD8 is recommended for the detection of specific antigens of interest in normal
and neoplastic tissues, as an adjunct to conventional histopathology using nonimmunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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CD10

CD11c

Human tonsil: immunohistochemical staining for CD10. Note membrane staining of germinal
centre B cells. CD10: clone 56C6

Human hairy cell leukemia: immunohistochemical staining for CD11c. CD11c: clone 5D11

5D11

56C6
FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0270P(HIER)

IVD

IVD

IVD

BOND 30 mL

PA0131

P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-CD10-270

P(HIER)

IVD

IVD

IVD/RUOSFORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0554P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-CD11c-563

P(HIER)

IVD

IVD

IVD/RUOPATHOLOGY MENUHEMATOPATHOLOGYPATHOLOGY MENUHEMATOPATHOLOGYANTIGEN BACKGROUND
CD11c is a member of the leukocyte integrin family of adhesion proteins. It isreported to be expressed in normal tissues, mainly on myeloid cells, for example,
in bone marrow myelocytes, premyelocytes, metamyelocytes, non-segmented
and segmented neutrophils with high levels reported on tissue macrophages
and monocytes and with lowest levels in granulocytes. It is also reported to be
expressed on NK cells, activated T cells, lymphoid cell lines, including hairy cellleukemias and a proportion of interdigitating dendritic cells.

ANTIGEN BACKGROUND
CD10 antigen, also called neprilysin, is a 100 kD cell surface metalloendopeptidase
which inactivates a variety of biologically active peptides. It was initially identified
as the common acute lymphoblastic leukemia antigen (CALLA) and was thought
to be tumor-specific. Subsequent studies, however, have shown that CD10 antigen
is expressed on the surface of a wide variety of normal and neoplastic cells. In
other lymphoid malignancies, CD10 antigen is reported to be expressed on cellsof lymphoblastic, Burkitt’s and follicular lymphomas. CD10 antigen has been
identified on the surface of normal early lymphoid progenitor cells, immature B
cells within adult bone marrow and germinal center B cells within lymphoid tissue.
It is also expressed in various non-lymphoid cells and tissues, such as breast
myoepithelial cells, bile canaliculi, fibroblasts, with especially high expression on
the brush border of kidney and gut epithelial cells. (G. McIntosh et al. American
Journal of Pathology. 154(1): 77-82 (1999)).

CD11c is recommended for the detection of specific antigens of interest in normal
and neoplastic tissues, as an adjunct to conventional histopathology using nonimmunologic histochemical stains.

CD10 is recommended for the detection of specific antigens of interest in normal
and neoplastic tissues, as an adjunct to conventional histopathology using nonimmunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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CD13

CD15

Human liver: immunohistochemical staining for CD13. Note staining of the bile canaliculi.
CD13: clone 38C12

Hodgkin’s disease, mixed cellularity: immunohistochemical staining for CD15.
CD15: clone MMA

38C12

MMA

I

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FORMAT

CODE

USAGE

US

EU

ROW*

FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0304P(HIER)

IVD

IVD

IVD

BOND 7 mL

PA0473P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-CD13-304

P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-CD15-605

P(HIER)

IVD

IVD

IVD

PATHOLOGY MENUPATHOLOGY MENUHEMATOPATHOLOGYHEMATOPATHOLOGYANTIGEN BACKGROUNDANTIGEN BACKGROUND

CD13 antigen, also known as aminopeptidase N, is a member of type II integral
membrane metalloproteases, which also includes the leukocyte antigens CD10,
CD26, CD73 and BP-1. CD13 antigen is a receptor for the coronaviruses whichcause respiratory disease in humans and several animal species. The antigen
functions as a zinc-binding metalloprotease which plays a role in cell surface
antigen presentation by trimming the N-terminal amino acids from MHC class
II-bound peptides. CD13 antigen is reported to be expressed on granulocytes,
monocytes and their precursors, most acute myeloid leukemias and a smaller
proportion of acute lymphoid leukemias. Non-hematopoietic cells which express
CD13 antigen include epithelial cells, renal proximal tubules, intestinal brushborder, endothelial cells, fibroblasts, brain cells, bone marrow, osteoclasts and cells
lining the bile canaliculi.

CD15 antigen, also known as X-hapten, is reported to be expressed on 90% of
circulating human granulocytes, 30-60% of circulating monocytes and is absent
from normal lymphocytes. The CD15 antigen is also expressed on Reed Sternberg
cells of Hodgkin’s disease and some leukemias.
CD15 is recommended for the detection of specific antigens of interest in normal
and neoplastic tissues, as an adjunct to conventional histopathology using nonimmunologic histochemical stains.

CD13 is recommended for the detection of specific antigens of interest in normal
and neoplastic tissues, as an adjunct to conventional histopathology using nonimmunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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CD16

CD19

Human colon, ulcerative colitis: immunohistochemical staining for CD16. CD16: clone 2H7

Human tonsil: immunohistochemical staining for CD19. Note membrane staining of B cells.
CD19: clone BT51E

2H7
FORMAT

CODE

USAGE

US

EU

ROW*

Liquid 1 mL

NCL-L-CD16

P(HIER)

IVD

IVD

IVD

S

BT51E
FORMAT

CODE

USAGE

US

EU

BOND 7 mL

ROW*

PA0843P(HIER)

IVD

IVD

IVD

PATHOLOGY MENU

Liquid 0.5 mL

NCL-L-CD19-163

P(HIER)

IVD

IVD

IVD/RUOHEMATOPATHOLOGY

Liquid 1 mL

NCL-L-CD19-163

P(HIER)

IVD

IVD

IVD/RUOPATHOLOGY MENUANTIGEN BACKGROUNDHEMATOPATHOLOGY

CD16 antigen has a molecular weight of 50 to 70 kD and is a low affinity Fc
receptor for complexed IgG, Fc/gamma RIII, expressed on natural killer (NK) cells,
granulocytes, activated macrophages and a subset of T cells expressing alphabeta or gamma-delta T cell antigen receptors. The CD16 antigen exists both as aglycosyl-phosphatidylinositol (GPI)-anchored protein in polymorphonuclear cells
and as a transmembrane protein in NK cells.

ANTIGEN BACKGROUND
CD19 is a member of the immunoglobulin superfamily and has two Ig like domains.
It is a single chain glycoprotein present on the surface of B lymphocytes andfollicular dendritic cells of the hematopoietic system. CD19 is a crucial regulator in
B cell development, activation and differentiation. On B cells, CD19 associates with
CD21, CD81 and CD225 (Leu-13) forming a signal transduction complex. CD19 isexpressed from the earliest recognizable B cell lineage stage, through development
to B cell differentiation but is lost on maturation to plasma cells.

CD16 is recommended for the detection of specific antigens of interest in normal
and neoplastic tissues, as an adjunct to conventional histopathology using nonimmunologic histochemical stains.

CD19 is recommended for the detection of specific antigens of interest in normal
and neoplastic tissues, as an adjunct to conventional histopathology using nonimmunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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CD20

CD21

Follicular B cell lymphoma. immunohistochemical staining for CD20. CD20: Clone L26

Human tonsil: immunohistochemical staining for CD21 antigen. Note intense membranestaining of follicular dendritic cells. CD21: clone 2G9

L26
FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0200P(HIER)

IVD

IVD

IVD

PA0359P(HIER)

IVD

IVD

IVD

Liquid 0.5 mL

NCL-L-CD20-L26

P(HIER)

IVD

IVD

IVD/RUO

Liquid 1 mL

NCL-L-CD20-L26

P(HIER)

IVD

IVD

IVD

BOND 30 mLS

2G9FORMAT

CODE

USAGE

US

EU

BOND 7 mL

ROW*

PA0171

P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-CD21-2G9

P(HIER)

IVD

IVD

IVD/RUOPATHOLOGY MENUHEMATOPATHOLOGYPATHOLOGY MENUHEMATOPATHOLOGYANTIGEN BACKGROUND
CD21 antigen is a type I integral membrane glycoprotein of molecular weight
140 kD, which functions as the receptor for the C3d fragment of the third
complement component. The CD21 molecule, present on mature B cells, isinvolved in transmitting growth-promoting signals to the interior of the B cell andacts as a receptor for Epstein-Barr virus. CD21 antigen is reported to be found in
B cell chronic lymphocytic leukemias and in a subset of T cell acute lymphocytic
leukemias but is absent on T lymphocytes, monocytes and granulocytes. CD21
antigen is also reported to be expressed in follicular dendritic cells and in follicularand mantle cell lymphomas, mature leukemias and lymphomas.

ANTIGEN BACKGROUNDThe CD20 antigen is a non-glycosylated phosphoprotein of approximately 33kD
which is expressed on normal and malignant human B cells and is thought to act
as a receptor during B cell activation and differentiation. CD20 antigen has beenreported to be expressed on normal B cells from peripheral blood, lymph node,
spleen, tonsil, bone marrow, acute leukemias and chronic lymphocytic leukemias.
CD20 is recommended for the detection of specific antigens of interest in normal
and neoplastic tissues, as an adjunct to conventional histopathology using nonimmunologic histochemical stains.

CD21 is recommended for the detection of specific antigens of interest in normal
and neoplastic tissues, as an adjunct to conventional histopathology using nonimmunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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CD22

CD23

Human tonsil: immunohistochemical staining for CD22. Note the mantle zone is staining
stronger than the germinal center. CD22: clone FPC1

Human tonsil: immunohistochemical staining for CD23. Note intense staining of folliculardendritic cell network and weaker staining of mantle zone cells. CD23: clone 1B12

FPC1

1B12

S

FORMAT

CODE

USAGE

US

EU

ROW*

FORMAT

CODE

USAGE

US

EU

BOND 7 mL

PA0249P(HIER)

IVD

IVD

IVD

BOND 7 mL

PA0169P(HIER)

IVD

IVD

IVD

Liquid 0.5 mL

NCL-L-CD23-1B12

P(HIER)

IVD

IVD

IVD/RUO

Liquid 1 mL

NCL-L-CD23-1B12

P(HIER)

IVD

IVD

IVD/RUOPATHOLOGY MENUHEMATOPATHOLOGYROW*

PATHOLOGY MENUANTIGEN BACKGROUNDHEMATOPATHOLOGYThe CD22 antigen (BL-CAM) is a type 1 integral membrane glycoprotein witha molecular weight of 130 to 140 kD. It is a heterodimer of two independently
expressed glycoprotein chains present both on the membrane and in the cytoplasmof B lymphocytes. Expression of the CD22 antigen is reported to appear early in
B cell lymphocyte differentiation at approximately the same stage as that of the
CD19 antigen expression. Surface antigen expression is variable and may be lost
upon differentiation. CD22 antigen is also reported to be weakly expressed on
myeloid leukemias and non-T cell acute lymphoblastic leukemias and is strongly
expressed on hairy cell leukemias. It is absent on peripheral blood T cells, T cellleukemias, granulocytes and monocytes.

ANTIGEN BACKGROUNDThe CD23 molecule is the low affinity IgE receptor found on B cells. It is amembrane glycoprotein of 45 kD and is reported to be found on a a sub-populationof peripheral blood cells, B lymphocytes and on EBV-transformed B lymphoblastoid
cell lines. Expression of CD23 antigen has been reported on monocytes anddendritic cells.
CD23 is recommended for the detection of specific antigens of interest in normal
and neoplastic tissues, as an adjunct to conventional histopathology using nonimmunologic histochemical stains.

CD22 is recommended for the detection of specific antigens of interest in normal
and neoplastic tissues, as an adjunct to conventional histopathology using nonimmunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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CD25

CD30

Human appendix: immunohistochemical staining for CD25. Note staining of activatedlymphocytes. CD25: clone 4C9

Human lymph node, nodular sclerosing Hodgkin’s disease: immunohistochemical staining forCD30. CD30: clone JCM182

4C9

JCM182S

FORMAT

CODE

USAGE

US

EU

ROW*

FORMAT

CODE

USAGE

US

EU

BOND 7 mL

PA0305P(HIER)

IVD

IVD

IVD

BOND 7 mL

PA0790P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-CD30-591

P(HIER)

IVD

IVD

IVD/RUOPATHOLOGY MENUHEMATOPATHOLOGYROW*

PATHOLOGY MENUHEMATOPATHOLOGYANTIGEN BACKGROUNDANTIGEN BACKGROUND

CD25 antigen, the alpha subunit of interleukin-2 receptor, is a single-chain
glycoprotein with a molecular weight of 55 kD. Following the activation of T
cells interleukin-2 (IL-2) is rapidly synthesized and secreted. In response tothis a subpopulation of T cells expresses high affinity receptors for IL-2. Thesecells proliferate, expanding the T cell population which is capable of mediating
helper, suppressor and cytotoxic functions. IL-2 receptor is not exclusively foundon T cells, and is reported to be expressed on HTLV-transformed T and B cells,
EBV-transformed B cells, myeloid precursors and oligodendrocytes. It is absent
on thymocytes, resting T cells, non-activated B cells and null cells. IL-2 receptor
expression is reported to be associated with inflammatory and malignant
conditions, lymphoid neoplasia, auto-immune diseases and allograft rejection.

The CD30 antigen is a single chain glycoprotein with a molecular weight of 120
kD. CD30 antigen is known to act as a receptor for a cytokine ligand, CD30L,
and may also play a role in the regulation of cellular growth and transformation.
CD30 antigen is reported to be expressed on the surface of multinucleated Reed
Sternberg cells, mononuclear Hodgkin’s cells and in the majority of anaplastic large
cell lymphomas. The CD30 antigen is expressed in non-Hodgkin’s lymphoma andvirally transformed cells, for example, EBV-transformed B cells.
CD30 is recommended for the detection of specific antigens of interest in normal
and neoplastic tissues, as an adjunct to conventional histopathology using nonimmunologic histochemical stains.

CD25 is recommended for the detection of specific antigens of interest in normal
and neoplastic tissues, as an adjunct to conventional histopathology using nonimmunologic histochemical stains.

PRODUCT SPECIFIC INFORMATION
Using retrieval solutions other than that recommended for clone JCM182 in thedatasheet may increase background reactivity.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

74

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CD31 (PECAM-1)

CD33

Human lymphoma: immunohistochemical staining for CD31. Note the membrane staining ofendothelial cells. CD31: Clone JC70A

Human lymph node, anaplastic lymphoma: immunohistochemical staining for CD33.
CD33: clone PWS44

JC70A

PWS44

E

S

FORMAT

CODE

USAGE

US

EU

ROW*

FORMAT

CODE

USAGE

US

EU

BOND 7 mL

PA0414P(HIER)

IVD

IVD

IVD

BOND 7 mL

ROW*

PA0555P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-CD31-607

P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-CD33

P(HIER)

IVD

IVD

IVD/RUOPATHOLOGY MENUPATHOLOGY MENUSOFT TISSUE PATHOLOGYHEMATOPATHOLOGYANTIGEN BACKGROUNDANTIGEN BACKGROUND

CD31 antigen (PECAM-1) is a single chain transmembrane glycoprotein witha molecular weight of 130 to 140 kD. The CD31 molecule is expressed on thesurface of platelets, monocytes, granulocytes, B cells and at the endothelial
intracellular junction. The molecule has an extracellular domain that contains six
Ig-like homology units of C2 subclass, typical of cell to cell adhesion molecules.
This domain mediates endothelial cell to cell adhesion, plays a role in endothelial
contact and may serve to stabilize the endothelial cell monolayer. The CD31
molecule also has a cytoplasmic domain with potential sites for phosphorylation
after cellular activation. The properties of CD31 antigen suggest that it is involved
in interactive events during angiogenesis, thrombosis and wound healing.
Angiogenesis is essential for tumor growth and metastases.

CD33 antigen is reported to appear on myelomonocytic precursor cells after CD34
antigen expression. It then continues to be expressed on both the myeloid andmonocyte lineages, although it is reported to be absent on granulocytes. It has
been reported that expression of CD33 is restricted to monocytes, premyelocytes,
myeloid blasts, some acute undifferentiated leukemias and acute lymphoblastic
leukemias.
CD33 is recommended for the detection of specific antigens of interest in normal
and neoplastic tissues, as an adjunct to conventional histopathology using nonimmunologic histochemical stains.

CD31 (PECAM-1) is recommended for the detection of specific antigens of interestin normal and neoplastic tissues, as an adjunct to conventional histopathology
using non-immunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

75

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CD34 (Endothelial Cell Marker)

CD38

Dermatofibrosarcoma protuberans: immunohistochemical staining for CD34.
CD34: clone QBEnd/10

Chronically inflamed human bronchus: immunohistochemical staining CD38.
CD38: clone SPC32

QBEnd/10

SPC32

I

E

FORMAT

CODE

USAGE

US

EU

ROW*

FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0212P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-CD38-290

P(HIER)

IVD

IVD

IVD

BOND 30 mL

PA0354P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-END

P(ENZYME)

IVD

IVD

IVD/RUOSPATHOLOGY MENUHEMATOPATHOLOGYPATHOLOGY MENUANTIGEN BACKGROUNDSOFT TISSUE PATHOLOGYThe CD38 molecule is a type II single transmembrane glycoprotein with amolecular weight of 46 kD. It is an ectoenzyme with the activities of ADP-ribosyl
cyclase, cyclic ADP-ribose hydrolase, NAD glycohydrolase and is involved in boththe formation and hydrolysis of cADPR, a second messenger that regulates themobilization of intracellular Ca2+ ions. Although the CD38 molecule was originallyidentified as a T lymphocyte differentiation antigen, it is reported to be expressedin a wide range of cells and tissues. CD38 antigen can deliver potent growth anddifferentiation signals to lymphoid and myeloid cells. It is found on immature cellsof the B and T cell lineages but not on most mature resting peripheral lymphocytes.
It is also present on thymocytes, pre-B cells, germinal center B cells, mitogenactivated T cells, Ig-secreting plasma cells, monocytes, NK cells, erythroid andmyeloid progenitors in the bone marrow and brain cells. CD38 antigen has also
been reported in neurofibrillary tangles, the pathological indicator of Alzheimer’s
disease that occurs in the neuronal perikarya and proximal dendrites.

ANTIGEN BACKGROUNDThe CD34 antigen is a single chain transmembrane glycoprotein with a molecularweight of 110 kD. The CD34 protein is selectively expressed in human lymphoidand myeloid hematopoietic progenitor cells. The CD34 antigen is also expressed in
vascular enothelium.
CD34 (Endothelial Cell Marker) is recommended for the detection of specificantigens of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.
PRODUCT SPECIFIC INFORMATION
Enzyme digestion of paraffin sections is recommended with clone QBEnd/10 inperference to heat induced epitope retrieval as it produces stronger staining andreduces background elastin staining

CD38 is recommended for the detection of specific antigens of interest in normal
and neoplastic tissues, as an adjunct to conventional histopathology using nonimmunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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CD43

CD45

Diffuse large B cell lymphoma: immunohistochemical staining for CD43. CD43: clone MT1

Human tonsil: immunohistochemical staining of CD45 or leukocyte common antigen (LCA) in
various hematolymphoid cells. CD45: clone X16/99

MT1
FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0938P(HIER)

IVD

IVD

IVD

NCL-L-MT1

P

IVD

RUO

RUO

Liquid 1 mLS

X16/99PATHOLOGY MENUHEMATOPATHOLOGYFORMAT

CODE

USAGE

US

EU

BOND 7 mL

ROW*

PA0042P(HIER)

IVD

IVD

IVD

Liquid 0.5 mL

NCL-L-LCAP(HIER)

IVD

IVD

IVD/RUO

Liquid 1 mL

NCL-L-LCAP(HIER)

IVD

IVD

IVD/RUOPATHOLOGY MENUHEMATOPATHOLOGYANTIGEN BACKGROUNDThe CD43 antigen is expressed on the membrane and in the cytoplasm of T
cells and cells of myeloid lineage. The molecule itself exhibits molecular weight
heterogeneity with bands of 90 to 140 kD observed on SDS-PAGE between different
cell lines. Cells expressing the CD43 antigen are reported to include normal andneoplastic T cells. A small proportion of B cell chronic leukemias and diffuse large
B cell lymphomas are also reported to express CD43 antigen.

ANTIGEN BACKGROUNDThe CD45 antigen (leukocyte common antigen) is a family of five or more highmolecular weight glycoproteins present on the surface of the majority of thehuman leukocytes (including lymphocytes, monocytes and eosinophils) but absent
from erythrocytes and platelets. Various isoforms of CD45 are generated byalternative splicing of three exons. Expression of CD45 is necessary for signaling
through the T cell receptor.

CD43 is recommended for the detection of specific antigens of interest in normal
and neoplastic tissues, as an adjunct to conventional histopathology using nonimmunologic histochemical stains.

CD45 is recommended for the detection of specific antigens of interest in normal
and neoplastic tissues, as an adjunct to conventional histopathology using nonimmunologic histochemical stains.

PRODUCT SPECIFIC INFORMATION
An enzyme pretreatment can be used to enhance staining in some cases.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

77

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CD45RO

CD56 (NCAM)

Human tonsil: immunohistochemical staining with CD45RO: clone UCHL1

Human tonsil: immunohistochemical staining for CD56. Note the NK cells and CD4/CD8 double
positive T cells show a weak to moderate and distinct membrane staining reaction while themajority of lymphocytes are unstained. CD56: clone CD564

UCHL1
FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0146P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-UCHL1

P(HIER)

RUO

RUO

RUO

CD564

PATHOLOGY MENUHEMATOPATHOLOGYFORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0191

P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-CD56-504

P(HIER)

IVD

IVD

IVD

PATHOLOGY MENUHEMATOPATHOLOGYANTIGEN BACKGROUNDThe CD45RO molecule, a 180 kD isoform of CD45, is reported to be expressedon 48% of peripheral blood T lymphocytes, 37% of CD4 positive lymphocytes,
80% of thymocytes and on the majority of T cell malignancies. Monocytes andgranulocytes show surface expression of the antigen whereas tissue macrophages
exhibit cytoplasmic expression.

ANTIGEN BACKGROUND
The neural cell adhesion molecules are a family of closely-related cell surface
glycoproteins thought to play a role in embryogenesis, development and contactmediated interactions between neural cells. The CD56 antigen (NCAM) consists offour major isoforms generated by differential splicing of the RNA transcript from asingle gene located on chromosome 5. The CD56 antigen is expressed on neurons,
astrocytes, Schwann cells, NK cells and a subset of activated T lymphocytes.

CD45RO is recommended for the detection of specific antigens of interest in
normal and neoplastic tissues, as an adjunct to conventional histopathology using
non-immunologic histochemical stains.

CD56 (NCAM) is recommended for the detection of specific antigens of interest in
normal and neoplastic tissues, as an adjunct to conventional histopathology using
non-immunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

78

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CD57

CD61 (GPIIIa)

Human tonsil: immunohistochemical staining of T lymphocytes. CD57: clone NK-1

Human tonsil: immunohistochemical staining of CD61 antigen (GPIIIa) on platelets within the
blood vessel. CD61 (GPIIIa): clone 2f2

NK-1
FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0443P(HIER)

IVD

IVD

IVD

S

2f2

PATHOLOGY MENUFORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0308P(HIER)

IVD

IVD

IVD

PATHOLOGY MENUHEMATOPATHOLOGYHEMATOPATHOLOGYANTIGEN BACKGROUNDANTIGEN BACKGROUNDThe CD57 glycoprotein, also known as HNK-1, has a molecular weight of 110 kD.
It is found on a subset of mononuclear cells with natural killer activity and on
neuroectodermal cells expressing myelin-associated glycoprotein. Many cells
which co-express CD57 and CD8 proteins are a subset of suppressor/cytotoxic
T cells. These cells play a role in the rejection of grafts in acute graft versus hostdisease. The CD57 molecule is not expressed on erythrocytes or platelets.

The CD61 antigen, also known as GPIIIa, is a glycoprotein of 105 kD found on
platelets, monocytes, endothelial cells, smooth muscle cells, B cells, macrophages,
mast cells and fibroblasts. CD61 antigen plays a role in platelet aggregation andalso as a receptor for fibrinogen, fibronectin, von Willebrand factor and vitronectin.
Individuals with Glanzmann’s thrombasthenia are reported to express little or no
CD61 antigen. CD61 antigen is also reported to be expressed in most cases ofmegakaryocytic leukemias.

CD57 is recommended for the detection of specific antigens of interest in normal
and neoplastic tissues, as an adjunct to conventional histopathology using nonimmunologic histochemical stains.

CD61 (GPIIIa) is recommended for the detection of specific antigens of interest in
normal and neoplastic tissues, as an adjunct to conventional histopathology using
non-immunologic histochemical stains.

PRODUCT SPECIFIC INFORMATION
An enzyme pretreatment can be used to enhance staining in some cases.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

79

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CD68

CD71

Human tonsil: immunohistochemical staining for CD68. Note the germinal centre macrophages
show a strong cytoplasmic staining reaction, while the interfollicular macrophages showcorrect weak to moderate staining reaction. CD68: clone 514H12

Human bone marrow: immunohistochemical staining for CD71. Note membrane staining oferythroid progenitor cells. CD71: clone 10F11

10F11514H12
FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0273P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-CD68

P(HIER)

IVD

IVD

IVD/RUOFORMAT

CODE

USAGE

US

EU

ROW*

Liquid 1 mL

NCL-L-CD71-309

P(HIER)

IVD

IVD

IVD

PATHOLOGY MENUSPECIALIZEDPATHOLOGY MENUHEMATOPATHOLOGYANTIGEN BACKGROUNDThe CD71 molecule is a type II membrane glycoprotein with a molecular weightof approximately 180 kD. It is known as the transferrin receptor and is composedof two disulfide-BONDed 90 kD subunits. The CD71 molecule plays a critical rolein cell proliferation by controlling the supply of iron, an essential component for
many metabolic pathways, through the binding and endocytosis of transferrin, themajor iron-carrying protein. CD71 protein is reported to be expressed on activated
B and T cells, macrophages, proliferating cells and metabolically active cells, forexample, neurons.

ANTIGEN BACKGROUNDThe CD68 molecule is a 110 kD intracellular glycoprotein primarily reported to
be associated with cytoplasmic granules and to a lesser extent the membranesof macrophages. Markers to CD68 antigen are the most frequently used for theidentification of macrophages in immunohistochemistry; however, CD68 is also
found in monocytes, neutrophils, basophils and large lymphocytes. The functionof the CD68 molecule is not certain but these lysosomal membrane proteins
are major components and may protect the membranes from attack by acidhydrolases. It is unclear if the surface-associated CD68 protein is functionallysignificant or due to leakage from the lysosomes. CD68 protein expression has
been demonstrated in stimulated T cells and NK cells and non-hematopoietic
tissues such as liver and renal tubules.

CD71 is recommended for the detection of specific antigens of interest in normal
and neoplastic tissues, as an adjunct to conventional histopathology using nonimmunologic histochemical stains.

CD68 is recommended for the detection of specific antigens of interest in normal
and neoplastic tissues, as an adjunct to conventional histopathology using nonimmunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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CD79a

CD79b

Human diffuse large B cell lymphoma: immunohistochemical staining for CD79a.
CD79a: clone JCB117

Human tonsil: immunohistochemical staining for CD79b. Note intense membrane stainingof B cells. CD79b: clone JS01

JCB117

JS01

FORMAT

CODE

USAGE

US

EU

ROW*

FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0599P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-CD79b

P(HIER)

RUO

RUO

RUO

Liquid 1 mL

NCL-L-CD79a-599

P(HIER)

IVD

IVD

IVD

PATHOLOGY MENUPATHOLOGY MENUHEMATOPATHOLOGYHEMATOPATHOLOGYANTIGEN BACKGROUNDANTIGEN BACKGROUND

CD79b, also known as B29 and Ig-beta is thought to function in the cellular
activation and signaling that occurs when surface immunoglobulin (Ig) on B cells
binds antigen or becomes cross-linked by anti-Ig antibody. This function occurs
with the formation of a membrane signaling complex that is associated with Ig
at the surface of B cells. CD79b, together with CD79a, forms the B cell antigen
receptor (mlg) complex.

The CD79 complex is a disulfide-linked heterodimer which is non-covalently
associated with membrane-bound immunoglobulins on B cells. This complex ofpolypeptides and immunoglobulin constitute the B cell antigen receptor. The twocomponents of this complex are designated CD79a and CD79b. The CD79a antigen
is reported to first appear at the pre-B cell stage, early in maturation, and persist
until the plasma cell stage where it is found as an intracellular component. It is notpresent in myeloid or T cell lines.
CD79a is recommended for the detection of specific antigens of interest in normal
and neoplastic tissues, as an adjunct to conventional histopathology using nonimmunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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CD99

CD103

Human tonsil: immunohistochemical staining for CD99. Note membrane staining of vessel
endothelium and a subpopulation of lymphocytes. CD99: clone PCB1

Human normal small bowel immunohistochemical staining of CD103. Note membrane andcytoplasmic staining of Intraepithelial T lymphocytes. CD103: clone EP206

PCB1

EP206

FORMAT

CODE

USAGE

US

EU

ROW*

FORMAT

CODE

USAGE

US

EU

ROW*

Liquid 1 mL

NCL-L-CD99-187

P(HIER)

IVD

IVD

IVD/RUO

BOND 7 mL

PA0374P(HIER)

IVD

IVD

IVD

PATHOLOGY MENUPATHOLOGY MENUSOFT TISSUE PATHOLOGYHEMATOPATHOLOGYSANTIGEN BACKGROUNDANTIGEN BACKGROUND

CD99 is a 32 kDa transmembrane glycoprotein, encoded by the MIC2 gene, which
is located in the pseudoautosomal region of the human X and Y chromosomes.
Recently, the MIC2 gene has been shown to encode two distinct proteins which areproduced by alternative splicing of the CD99 gene transcript and are identified as
bands of 30 and 32 kDa (p30/32).

CD103, also known as alpha E integrin and human mucosal lymphocyte antigen 1,
is an integrin protein with expression on intraepithelial T cells and some peripheral
regulatory T cells. CD103 is expressed at high levels on tumor-infiltrating FOXP3positive regulatory T cells in cancer. CD103-positive T cells are strongly associatedwith patient survival in high-grade serous ovarian cancer. CD103 expression has
been suggested as a definitive marker of intraepithelial, tumor-specific infiltrating
lymphocytes. In addition, CD103-positive cells have also been identified in a small
proportion of breast cancers.

CD99 is recommended for the detection of specific antigens of interest in normal
and neoplastic tissues, as an adjunct to conventional histopathology using nonimmunologic histochemical stains.

CD103 is recommended for the detection of specific antigens of interest in normal
and neoplastic tissues, as an adjunct to conventional histopathology using nonimmunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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CD117

CD123

Human colon, gastrointestinal stromal tumor: immunohistochemical staining for CD117.
CD117: clone EP10

Human high walled venule endothelium and plasmacytoid dendritic cells:
immunohistochemical staining for CD123: clone BR4MS

EP10

BR4MS

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CODE

USAGE

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EU

ROW*

FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0007P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-CD123

P(HIER)

IVD

IVD

IVD/RUO

Liquid 1 mL

NCL-L-CD117-032

P(HIER)

IVD

IVD

IVD

PATHOLOGY MENUPATHOLOGY MENUHEMATOPATHOLOGYGASTROINTESTINAL PATHOLOGYANTIGEN BACKGROUNDANTIGEN BACKGROUNDThe CD123 antigen is also known as the alpha subunit of the human interleukin-3
receptor. It is a type I transmembrane glycoprotein and is a member of the cytokine
receptor superfamily. CD123 forms a heterodimer with CD131 (the beta subunitof the interleukin-3 receptor) to form the interleukin-3 receptor, where the cytokine
specificity is provided by the alpha subunit and the signal transduction function isprovided by the beta subunit. The interleukin-3 receptor is reported to be expressedon monocytes, neutrophils, basophils, eosinophils, megakaryocytes, erythroid
precursors, mast cells, macrophages and a subpopulation of B cells, where it
mediates proliferation and differentiation of these cells. Outside the hematopoietic
system CD123 is reported to be expressed in Leydig cells of the testis, someendothelial cells, and cells of the placenta and brain.

The c-kit proto-oncogene encodes a transmembrane receptor with tyrosine kinase
activity, c-kit (CD117), which is closely-related to the platelet-derived growth
factor receptor family. c-kit plays a role during hematopoiesis, gametogenesis andmelanogenesis. The expression of CD117 antigen is of particular interest in the
study of gastrointestinal stromal tumors (GIST), small lung cell carcinomas and inmelanomas.
CD117 is recommended for the detection of specific antigens of interest in normal
and neoplastic tissues, as an adjunct to conventional histopathology using nonimmunologic histochemical stains.

CD123 is recommended for the detection of specific antigens of interest in normal
and neoplastic tissues, as an adjunct to conventional histopathology using nonimmunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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CD138 (Syndecan 1)

CD141 (Thrombomodulin)

Plasmacytoma: immunohistochemical staining for CD138. CD138: clone MI15

Human tonsil: immunohistochemical staining for CD141. Note membrane staining of the basal
cells of the squamous mucosa, endothelium and a subset of dentritic cells. CD141: clone 15C8MI15FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0088P(HIER)

IVD

IVD

IVD

15C8

PATHOLOGY MENUFORMAT

CODE

USAGE

US

EU

ROW*

Liquid 1 mL

NCL-L-CD141

P(HIER)IVD--

PATHOLOGY MENUHEMATOPATHOLOGY

SPECIALIZEDANTIGEN BACKGROUNDANTIGEN BACKGROUNDThe CD138 molecule is a transmembrane heparan sulphate glycoprotein expressedat distinct stages of differentiation in normal lymphoid cells such as pre-B cells,
immature B cells and Ig-producing plasma cells as well as being expressedin stratified and simple epithelia. The loss of CD138 expression from atypicalcells is reported to be an early event during cervical carcinogenesis whereas
CD138 antigen expression shows a close association with preserved epithelial
morphology and differentiation; however, the major utility of CD138 as a marker in
immunohistochemistry is the quantification of plasma cells.

Thrombomodulin is a transmembrane glycoprotein of 75 kD which can accelerate
the activation of protein C. Activated protein C functions as an anticoagulant
by combining with protein S to inactivate factors Va and VIIIa of the blood
coagulation pathway and by binding thrombin. Several factors regulate
thrombomodulin expression. Downregulation of thrombomodulin may be inducedby the cytokine interleukin-1, tumor necrosis factor and endotoxin. Agents which
increase cyclic AMP such as forskolin may upregulate thrombomodulin activity
in endothelial cells. Thrombomodulin has been identified within a number ofnormal tissues. These include the lining cells of arteries, veins, capillaries andthe lymphatics as well as mesothelial cells, meningeal lining cells, synovial cells,
syncytiotrophoblasts, megakaryocytes and platelets.

CD138 (Syndecan 1) is recommended for the detection of specific antigens
of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

CD141 (Thrombomodulin) is recommended for the detection of specific antigens
of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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CD146 (MCAM)

CD163

Human malignant melanoma: immunohistochemical staining for CD146. CD146: clone N1238

Human placenta: immunohistochemical staining for CD163. Note cytoplasmic staining of
Hofbauer cells. CD163: clone 10D6N1238
FORMAT

CODE

USAGE

US

EU

ROW*

Liquid 1 mL

NCL-L-CD146

P(HIER)

IVD

-

-

S

10D6

PATHOLOGY MENU
DERMATOPATHOLOGYFORMAT

CODE

USAGE

US

EU

BOND 7 mL

ROW*

PA0090P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-CD163

P(HIER)

IVD

IVD

IVD/RUOPATHOLOGY MENUHEMATOPATHOLOGYANTIGEN BACKGROUND
CD146 protein is also known as the melanoma metastasis-associated surface
molecule, MUC18, A32 antigen, S-Endo-1 and the melanoma cell adhesion
molecule, MCAM or Mel-CAM. Originally, the CD146 molecule was defined as amarker of tumor progression and metastasis formation in human melanoma. Morerecently, it has been reported to be expressed on endothelial cells, smooth muscle
and cerebellar cortex. Structurally, CD146 is an integral membrane glycoprotein of
113 kD with the characteristic V-V-C2-C2-C2 immunoglobulin-like domain structure.
It shares considerable homology with chicken neural adhesion molecule, chicken
gicerin, goldfish neurolin and is also closely related to the human blood groupglycoprotein, lutheran. Although CD146 molecule functions as a cell adhesion
molecule it interacts with an as yet uncharacterized ligand. CD146 can be inducedon all T cells via PHA, recall antigen, superantigen and T cell receptor/CD3
stimulation. Furthermore reports suggest that the CD146 molecule is involved in
the extravasation and homing of activated T cells. CD146 protein can promotetumor progression in human melanoma, possibly through enhanced interaction
between melanoma cells and endothelial cells. In contrast, CD146 protein may act
as a tumor suppressor in breast carcinoma with expression frequently lost in somecases.

ANTIGEN BACKGROUNDThe CD163 molecule is a type I membrane protein also known as M130 antigen,
Ber-Mac3, Ki-M8 or SM4. CD163 protein is restricted in its expression to themonocytic/macrophage lineage. It is reported to be present on all circulating
monocytes and most tissue macrophages except those found in the mantle
zone and germinal centers of lymphoid follicles, interdigitating reticulum cells
and Langerhans cells. In addition, multi-nucleated cells within inflammatory
lesions are reported not to express CD163 protein. The protein is upregulated by
glucocorticoids and downregulated by the immunosuppressant cyclosporin A andby phorbol esters, while lipopolysaccharide, an inflammatory mediator, has noinfluence on expression. It has been proposed that a specific release mechanismof soluble CD163 antigen by human monocytes may play an important role inmodulating inflammatory processes.
CD163 is recommended for the detection of specific antigens of interest in normal
and neoplastic tissues, as an adjunct to conventional histopathology using nonimmunologic histochemical stains.

CD146 (MCAM) is recommended for the detection of specific antigens of interestin normal and neoplastic tissues, as an adjunct to conventional histopathology
using non-immunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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CDX2

c-erbB-2 Oncoprotein (HER-2) Antibodies

Human colonic adenocarcinoma: immunohistochemical staining for CDX2. CDX2: clone EP25

Human breast: invasive ductal carcinoma: immunohistochemical staining for c-erbB-2
Oncoprotein (HER-2): clone CB11

EP25
FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0375P(HIER)

IVD

IVD

IVD

CB11
FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0983P(HIER)

IVD

IVD

IVD

PATHOLOGY MENU

BOND 30 mL

PA0571

P(HIER)

IVD

IVD

IVD

GASTROINTESTINAL PATHOLOGY

Liquid 1 mL

NCL-L-CB11

P

-

IVD

IVD

ANTIGEN BACKGROUND

10A7

CDX2 is a caudal-type homeobox, intestine-specific transcription factor
expressed early in intestinal development and may be involved in the regulation of
proliferation and differentiation of intestinal epithelial cells. CDX2, as well as CDX1,
is of particular interest as the intestine is the only organ that contains detectablelevels of either gene product.

FORMAT

CODE

USAGE

US

EU

ROW*

Liquid 1 mL

NCL-L-CBE-356

P

-

IVD

IVD/RUOPATHOLOGY MENU
BREAST PATHOLOGYThis pattern of restricted expression is unusual for homeobox genes.
Phosphorylation of the CDX2 activation domain can modulate its function anddifferent spatial expression patterns in the intestinal epithelium. CDX2 is primarily
expressed on the surface of the villus and in the crypts. In contrast to CDX1,
intense CDX2 expression is reported to occur in all but the distal portions of thedeveloping intestine.

ANTIGEN BACKGROUND
The c-erbB-2 oncoprotein is closely related in structure to the epidermal growth
factor receptor and is a member of a large family of cell surface growth factor
receptors. c-erbB-2 oncoprotein is reported to be detectable in a proportion ofbreast and other adenocarcinomas as well as transitional cell carcinomas. c-erbB-2
oncoprotein is present in a wide variety of cell types in a range of normal human
fetal and adult tissues, including breast, stomach and ovary. CB11 detects theinternal domain of the c-erbB-2 oncoprotein. CBE-356 detects the external domainof the c-erbB-2 oncoprotein.

The loss of CDX2 has been reported to contribute towards the progression ofsome sporadic colorectal cancers. It has been reported that CDX2 may also be
associated with carcinogenesis of the stomach as expression of CDX2 mRNA
progressively decreases with the transition from well differentiated to poorly
differentiated gastric cancer cell lines.

c-erbB-2 Oncoprotein (HER-2) Antibodies are recommended for the detection of
specific antigens of interest in normal and neoplastic tissues, as an adjunct toconventional histopathology using non-immunologic histochemical stains.

CDX2 is recommended for the detection of specific antigens of interest in normal
and neoplastic tissues, as an adjunct to conventional histopathology using nonimmunologic histochemical stains.

PRODUCT SPECIFIC INFORMATIONThe use of the heat induced epitope retrieval (HIER) technique can enhance
staining in some cases.
INTENDED USEThis reagent is for in vitro diagnostic use. The c-erbB-2 Oncoprotein (CB11)
monoclonal antibody is intended to be used for the qualitative identification by
light microscopy of c-erbB-2 oncoprotein in formalin-fixed, paraffin-embedded
tissue by immunohistochemical staining.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Chromogranin A

Cyclin D1

Human small bowel: immunohistochemical staining for Chromogranin A. Note cytoplasmic
staining of neuroedocrine cells. Chromogranin A: clone 5H7

Human mantle cell lymphoma: immunohistochemical staining for Cyclin D1.
Cyclin D1: clone EP12

5H7

EP12

I

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FORMAT

CODE

USAGE

US

EU

ROW*

FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0515P(HIER)

IVD

IVD

IVD

BOND 7 mL

PA0046P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-CHROM-430

P(HIER)

IVD

IVD

IVD

S

P2D11F11

PATHOLOGY MENUFORMAT

CODE

HEAD, NECK AND ENDOCRINE

Liquid 1 mL

NCL-L-CYCLIND1-GM P(ENZYME/HIER)USAGE

ANTIGEN BACKGROUNDPATHOLOGY MENU

Chromogranin A is a 68 kD acidic protein which is reported to be widely expressedin neural tissues and in secretory granules of human endocrine cells, forexample, parathyroid gland, adrenal medulla, anterior pituitary gland, islet cellsof the pancreas and C cells of the thyroid. Chromogranin A expression has beenreported in neuroendocrine tumors such as pituitary adenomas, islet cell tumors,phaeochromocytomas, medullary thyroid carcinomas, Merkel cell tumors andcarcinoids.

HEMATOPATHOLOGY

US

EU

ROW*

IVD

IVD

IVD/RUO

ANTIGEN BACKGROUND
The D-type cyclins are a family of proteins which function primarily by regulating
the activity of cyclin dependent kinases in the G1 phase of the cell cycle. Cyclin D1,
a protein of 36 kD, is also known as PRAD1 or bcl-1. Maximum expression of cyclin
D1 occurs at a critical point in mid to late G1 phase of the cell cycle. The cyclin
D1 gene, located on 11q13 has been reported to be overexpressed in mantle cell
lymphomas due to the chromosomal translocation t(11;18).

Chromogranin A is recommended for the detection of specific antigens of interestin normal and neoplastic tissues, as an adjunct to conventional histopathology
using non-immunologic histochemical stains.

Cyclin D1 is recommended for the detection of specific antigens of interest in
normal and neoplastic tissues, as an adjunct to conventional histopathology using
non-immunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Cytokeratin 5

Cytokeratin 7

Human breast, ductal carcinoma in situ: immunohistochemical staining for Cytokeratin 5.
Cytokeratin 5: clone XM26

Invasive breast carcinoma: immunohistochemical staining for Cytokeratin 7.
Cytokeratin 7: clone RN7

XM26

RN7

I

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FORMAT

CODE

USAGE

US

EU

ROW*

FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0468P(HIER)

IVD

IVD

IVD

BOND 7 mL

PA0942P(HIER)

IVD

IVD

IVD

Liquid 0.5 mL

NCL-L-CK5

P(HIER)

IVD

IVD

IVD/RUO

BOND 30 mL

PA0138P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-CK5

P(HIER)

IVD

IVD

IVD/RUO

Liquid 1 mL

NCL-L-CK7-560

P(HIER)

IVD

IVD

IVD/RUOPATHOLOGY MENUPATHOLOGY MENU

UROPATHOLOGYTUMOR DIFFERENTIATIONANTIGEN BACKGROUNDANTIGEN BACKGROUND

Cytokeratins are a large family of cytoskeletal proteins found in epithelial cells.
They are co-ordinately synthesized in pairs so that at least one member of eachfamily is expressed in each epithelial cell. Cytokeratins assemble into obligatory
heteropolymers composed of type I (acidic) and type II (basic) polypeptides toform higher order tetramers and protofilaments. Basal cells of human epidermis
express acidic keratin 14 and basic cytokeratin 5. Cytokeratin 5 is a 58 kD proteinthat is closely related to cytokeratin 6. They share similar tissue distribution andare found in various proportions in many non-keratinizing stratified squamous
epithelia, for example, tongue mucosa, as well as in basal epithelia of trachea,basal cells of epidermis, hair follicles, sebaceous and sweat glands of skin,luminal cells of the mammary gland, basal cells of prostate, urothelium, vagina
and endocervical mucosa. Cytokeratins 5 and 6 are also expressed in basal cellepitheliomas, squamous cell carcinomas of skin, tongue, epiglottis and of therectal-anal region. Point mutations in the cytokeratin 5 gene at locus 12q11-q13
can cause various types of epidermolysis bullosa simplex. Cytokeratin 5 is also
reported to be expressed in most epithelial and biphasic mesotheliomas.

Cytokeratins are intermediate filament proteins present in epithelial cells. They
are expressed in a tissue-specific manner in normal organs and the tumors thatarise from them. Cytokeratin 7 belongs to the neutral basic type B subfamily ofcytokeratins. Its distribution is confined to glandular and transitional epithelia.
Cytokeratin 7 is reported to be expressed in abundance in cultured bronchial andmesothelial cells but only at lower levels in cultured epidermal cells. The predicted
amino acid sequence of this keratin has revealed a striking difference between
this keratin and the type II keratins expressed in epidermal cells. Cytokeratin 7
has been reported in adenocarcinomas of the lung, breast, endometrium, ovary,thyroid as well as in carcinomas of the bladder and chromophobe renal cell
carcinoma. Cytokeratin 7 and Cytokeratin 20 expression have been reported
to show characteristic patterns on primary and metastatic lung and colorectal
adenocarcinomas.
Cytokeratin 7 is recommended for the detection of specific antigens of interest in
normal and neoplastic tissues, as an adjunct to conventional histopathology using
non-immunologic histochemical stains.

Cytokeratin 5 is recommended for the detection of specific antigens of interest in
normal and neoplastic tissues, as an adjunct to conventional histopathology using
non-immunologic histochemical stains.

PRODUCT SPECIFIC INFORMATION
Where clone OV-TL 12/30 can produce unwanted staining of endothelial cells,clone RN7 does not stain these cell types. The choice of epitope retrieval, heat or
enzyme, to provide the best result with clone OV-TL 12/30 should be determined
and validated by the user. Clones RN7 and OV-TL 12/30 react with the humancytokeratin intermediate filament protein (54 kD) identified as cytokeratin 7.

PRODUCT SPECIFIC INFORMATION
Clone XM26 is specific for the 58 kD intermediate filament protein known ascytokeratin 5. It is not cross-reactive with cytokeratin 6.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Cytokeratin 8

Cytokeratin 14

Immunohistochemical staining for Cytokeratin 8: clone TS1

Invasive breast cancer: immunohistochemical staining for the Cytokeratin 14.
Cytokeratin 14: clone LL002

TS1
FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0567P(HIER)

IVD

IVD

IVD

ASR

RUO

RUO

Liquid 1 mL

NCL-L-CK8-TS1

-

I

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S

LL002

PATHOLOGY MENU
TUMOR DIFFERENTIATIONFORMAT

CODE

USAGE

US

EU

BOND 7 mL

ROW*

PA0074P(HIER)

IVD

IVD

IVD

Liquid 0.5 mL

NCL-L-LL002

P(HIER)

IVD

IVD

IVD/RUO

Liquid 1 mL

NCL-L-LL002

P(HIER)

IVD

IVD

IVD/RUOPATHOLOGY MENUANALYTE SPECIFIC REAGENTTUMOR DIFFERENTIATION

Analyte Specific Reagent. Analytical and performance characteristics are notestablished.

ANTIGEN BACKGROUND
Cytokeratins 14 and 5 are useful to distinguish stratified epithelial cell types from
simple epithelial cell types. Cytokeratin 14 has been reported to be expressed inneoplasms of squamous cell origin.
Cytokeratin 14 is recommended for the detection of specific antigens of interest in
normal and neoplastic tissues, as an adjunct to conventional histopathology using
non-immunologic histochemical stains.
PRODUCT SPECIFIC INFORMATION
Clone LL002 reacts with the human cytokeratin intermediate filament protein (50kD) identified as cytokeratin 14.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Cytokeratin 17

Cytokeratin 18

Human squamous cell carcinoma, floor of the mouth: immunohistochemical staining for
Cytokeratin 17. Cytokeratin 17: clone E3

Human colonic adenocarcinoma: immunohistochemical staining for Cytokeratin 18.
Cytokeratin 18: clone DC-10

E3

DC-10

E

S

FORMAT

CODE

USAGE

US

EU

ROW*

FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0114P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-CK18

P(HIER)

IVD--

Liquid 1 mL

NCL-L-CK17

P(HIER)

IVD

IVD

IVD

PATHOLOGY MENUPATHOLOGY MENU

TUMOR DIFFERENTIATIONTUMOR DIFFERENTIATIONANTIGEN BACKGROUNDANTIGEN BACKGROUND

Cytokeratin 18 is normally co-expressed with cytokeratin 8 and is found in most
simple ductal and glandular epithelia.

In normal tissues cytokeratin 17 is reported to be expressed in basal cells ofcomplex epithelia, for example, basal cells of pseudostratified epithelium in the
trachea, larynx, bronchi, myoepithelial cells in salivary glands and sweat glands.
In neoplastic tissue, cytokeratin 17 is reported to be expressed in squamous cell
carcinomas of the lung, cervix and oral cavity.

Cytokeratin 18 is recommended for the detection of specific antigens of interest in
normal and neoplastic tissues, as an adjunct to conventional histopathology using
non-immunologic histochemical stains.
PRODUCT SPECIFIC INFORMATION

Cytokeratin 17 is recommended for the detection of specific antigens of interest in
normal and neoplastic tissues, as an adjunct to conventional histopathology using
non-immunologic histochemical stains.

CK18 reacts with the acidic cytokeratin intermediate filament protein (45 kD)
identified as cytokeratin 18. Cytokeratin 18 is reported not to be expressed instratified squamous epithelium on most squamous cell carcinomas.

PRODUCT SPECIFIC INFORMATIONCK17 reacts with the human cytokeratin intermediate filament protein (46 kD)
identified as cytokeratin 17.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Cytokeratin 19

Cytokeratin 20

Human rectal adenocarcinoma: immunohistochemical staining for Cytokeratin 19.
Cytokeratin 19: clone b170

Human colon: immunohistochemical staining for Cytokeratin 20. Note the intense staining of
surface mucosa. Cytokeratin 20: clone Ks.20.8

b170

Ks20.8S

FORMAT

CODE

USAGE

US

EU

ROW*

FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0799P(ENZYME)

IVD

IVD

IVD

BOND 7 mL

PA0022P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-CK19

P(HIER)

IVD--

BOND 30 mL

PA0037P(HIER)

IVD

IVD

IVD

Liquid 0.5 mL

NCL-L-CK20

P(HIER)

IVD

IVD

IVD/RUO

Liquid 1 mL

NCL-L-CK20

P(HIER)

IVD

IVD

IVD/RUOFORMAT

CODE

USAGE

US

EU

ROW*

Liquid 1 mL

NCL-L-CK20-561

P(HIER)

IVD

IVD

IVD

PATHOLOGY MENU
TUMOR DIFFERENTIATIONPW31ANTIGEN BACKGROUND
The smallest human cytokeratin filament protein (40 kD) has been identified
as cytokeratin 19 and has been reported to be expressed in a large number ofepithelial cell types, including many ductal and glandular epithelia.

PATHOLOGY MENU

Cytokeratin 19 is recommended for the detection of specific antigens of interest in
normal and neoplastic tissues, as an adjunct to conventional histopathology using
non-immunologic histochemical stains.

TUMOR DIFFERENTIATIONANTIGEN BACKGROUNDPRODUCT SPECIFIC INFORMATION

Cytokeratin 20 has been demonstrated to be almost entirely confined to the gastricand intestinal epithelium, urothelium and Merkel cells of the skin. Cytokeratin 20
is less acidic than other type I cytokeratins and is of interest due to its restrictedtissue expression. In normal tissue, cytokeratin 20 is expressed in intestinal
epithelium, gastric foveolar epithelium, a number of endocrine cells in the upper
portions of the pyloric glands, urothelium and Merkel cells in epidermis. In tumors
it is reported, there is a marked difference in the expression of cytokeratin 20
within different carcinomas. Neoplasms expressing cytokeratin 20 are derived
from normal epithelia which themselves expressed cytokeratin 20. Colorectal
carcinomas consistently express cytokeratin 20, while gastric adenocarcinomas
express cytokeratin 20 to a lesser degree. Adenocarcinomas of the gall bladderand bile duct, ductal cell adenocarcinomas of the pancreas, mucinous ovarian
tumors, Merkel cell tumors and transitional cell carcinomas have also beenreported to express cytokeratin 20.

Clone b170 produces a complex heterogeneous staining pattern in non-keratinizing
squamous epithelia and hair follicles, with strong staining of the basal layer
observed.

Cytokeratin 20 is recommended for the detection of specific antigens of interest in
normal and neoplastic tissues, as an adjunct to conventional histopathology using
non-immunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Cytokeratin (5/6/18)

Cytokeratin (8/18)

Human skin: immunohistochemical staining of LP34 (cytokeratins 5/6/18) localized
throughout the epidermis, with the strongest staining in the stratum spinosum. There is anabsence of staining in the dermis. Cytokeratin (5/6/18): clone LP34

Colon mucosa: immunohistochemical staining for Cytokeratin 8/18: clone 5D3

I

E

S

5D3

LP34

FORMAT

CODE

USAGE

US

EU

ROW*

FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0067P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-LP34

P(ENZYME)

IVD

RUO

RUO

Liquid 1 mL

NCL-L-5D3P(ENZYME)

IVD

IVD

IVD

PATHOLOGY MENUPATHOLOGY MENU

UROPATHOLOGYTUMOR DIFFERENTIATIONANTIGEN BACKGROUNDANTIGEN BACKGROUND

Cytokeratins 5, 6 and 18 are reported to be expressed in a broad range of humanepithelial tissues, from simple glandular epithelia to stratified squamous epithelia.
These include epithelial cells that are ectodermal, mesodermal, or endodermal inorigin. These cytokeratins have been reported to be expressed in tumor cells ofepithelial origin and less commonly of mesothelial origin. Non-epithelial tumors
such as lymphomas do not express these cytokeratins.

In normal tissues, cytokeratins 8 and 18 are reported to be expressed in all simple
and glandular epithelium and in neoplastic tissues, they have been reported to
be expressed in adenocarcinomas and most squamous cell carcinomas. These
cytokeratins are absent from keratinizing squamous carcinomas.
Cytokeratin (8/18) is recommended for the detection of specific antigens
of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

Cytokeratin (5/6/18) is recommended for the detection of specific antigens
of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

PRODUCT SPECIFIC INFORMATION
Clone 5D3 reacts with human cytokeratin intermediate filament proteins of 52.5
kD and 45 kD, identified as cytokeratins 8 and 18, respectively. Clone 5D3 shares
similar specificities to clone CAM5.2 (Angus B et al. Journal of Pathology. 153:
377-384 (1987)).

PRODUCT SPECIFIC INFORMATIONThe recognition of cytokeratin 18 on formalin fixed paraffin embedded sections
using clone LP34 may be variable.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Cytokeratin, Multi (1/5/10/14)(High Molecular Weight)

Cytokeratin, Multi (4/5/6/8/10/13/18)

Human prostate: immunohistochemical staining of the basal cells of the prostate with anticytokeratin (high molecular weight) antibody. Cytokeratin, Multi (1/5/10/14): clone 34βE12Human tonsil: immunohistochemical staining for cytokeratin, Multi. Note the cytokeratinsdemonstrated in stratified squamous epithelium. The negative cells in the epithelium are
infiltrating lymphocytes. Cytokeratin, Multi (4/5/6/8/10/13/18): clone C-11

34βE12
FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0134P(ENZYME)

IVD

IVD

IVD

C-11

PATHOLOGY MENUFORMAT

CODE

USAGE

US

EU

ROW*

Liquid 1 mL

NCL-L-C11

P(HIER)IVD--

PATHOLOGY MENU

TUMOR DIFFERENTIATIONTUMOR DIFFERENTIATIONANTIGEN BACKGROUNDANTIGEN BACKGROUND

34βE12 reacts with human cytokeratin intermediate filament proteins 1, 5, 10 and
14. The antibody is reported to react with squamous epithelium and sweat ducts innormal skin, some pneumocytes, bronchial epithelium and mesothelium in normallung and bile ducts in normal liver. It also reacts with ductal cells of the normal
pancreas, some acinar and ductal cells of normal breast, some follicular epitheliaof normal thyroid and some epithelia and mesothelium of the normal small andlarge bowel.

Cytokeratins 4, 5, 6, 8, 10, 13 and 18 are differentially expressed between a variety
of normal, reactive and neoplastic epithelia and also simple epithelium and bothbasal and suprabasal layers of cornifying and noncornifying squamous epithelium.
Cytokeratin, Multi (4/5/6/8/10/13/18) is recommended for the detection of
specific antigens of interest in normal and neoplastic tissues, as an adjunct toconventional histopathology using non-immunologic histochemical stains.

Cytokeratin, Multi (1/5/10/14) is recommended for the detection of specificantigens of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Cytokeratin, Multi (5/6/8/18)

Cytokeratin, Multi (AE1/AE3)

Human squamous cell carcinoma of the floor of the mouth: immunohistochemical staining forcytokeratins. Cytokeratin, Multi (5/6/8/18): clone 5D3/LP34

Human invasive ductal carcinoma of breast: immunohistochemical staining for AE1/AE3.
Multi-Cytokeratin: clone AE1/AE3

5D3/LP34

AE1/AE3

FORMAT

CODE

USAGE

US

EU

ROW*

FORMAT

CODE

USAGE

US

EU

ROW*

Liquid 1 mL

NCL-L-CK5/6/8/18

P(ENZYME)

RUO

RUO

RUO

BOND 7 mL

PA0094P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-AE1/AE3-601

P(HIER)

IVD

IVD

IVD

PATHOLOGY MENU
TUMOR DIFFERENTIATIONS

AE1/AE3 (Previous Formulation)

ANTIGEN BACKGROUND
CK5/6/8/18 reacts with human cytokeratins 5, 6, 8 and 18. These products are
cocktails of monoclonal antibodies designed to recognize cytokeratins reported to
be expressed in almost all epithelial tissues.

FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0909P(ENZYME)

IVD

IVD

IVD

PATHOLOGY MENU
TUMOR DIFFERENTIATIONANTIGEN BACKGROUND
Keratins are a family of water insoluble proteins of 40 to 70 kD. These proteins
form tonofilaments, a class of intermediate filament, in epidermis as well as inalmost all other epithelia. The process of normal epidermal differentiation ischaracterized by a series of morphological and biochemical changes as cells
progress from the germinative basal layer through the spinous and granular layers
to the outer cornified layer. The 65 to 67 kD cytokeratins are reported to be present
only above the basal layer, the 58 kD cytokeratin is reported to be expressed
throughout the entire epidermis including the basal layer and the 56 kD cytokeratin
is reported to be absent from the basal layer and is normally eliminated during
stratum corneum formation. The 56 and 65 to 67 kD cytokeratins are reported to
be characteristic of epidermal cells undergoing terminal differentiation and may beconsidered as molecular markers for keratinization.
Cytokeratin, Multi (AE1/AE3) is recommended for the detection of specificantigens of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.
PRODUCT SPECIFIC INFORMATION
Clones AE1 and AE3 are specific for the 56.5, 50, 50’, 48 and 40 kD acidic
cytokeratins as well as the 65 to 67, 64, 59, 58, 56 and 52 kD basic cytokeratins.
The cocktail of clones AE1 and AE3 exhibit broad reactivity with two families ofcytokeratin, acidic and basic.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Desmin

DOG-1

Human bowel: immunohistochemical staining for desmin. Note cytoplasmic staining ofsmooth muscle containing cells. Desmin: clone DE-R-11

Human colon, gastrointestinal stromal tumor: immunohistochemical staining for DOG-1. DOG1: clone K9

DE-R-11

K9

FORMAT

CODE

USAGE

US

EU

ROW*

FORMAT

CODE

USAGE

US

EU

BOND 7 mL

PA0032P(HIER)

IVD

IVD

IVD

BOND 7 mL

ROW*

PA0219P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-DES-DERIIP(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-DOG-1

P(HIER)

IVD

IVD

IVD/RUOPATHOLOGY MENUPATHOLOGY MENUSOFT TISSUE PATHOLOGYGASTROINTESTINAL PATHOLOGYANTIGEN BACKGROUNDANTIGEN BACKGROUND

DES-DERII reacts with an 18 kD rod piece of the intermediate filament protein
desmin (53 kD) in muscle cells. The antibody does not appear to recognize otherintermediate filament proteins. In normal tissues, Clone DE-R-11 reacts with bothstriated (skeletal and cardiac) and smooth muscle cells. The labeling is confinedto the Z bands in skeletal and cardiac muscle giving a characteristic striatedappearance.

DOG-1, a 986 amino acid protein of unknown function, is expressed predominantly
on the plasma membrane of gastrointestinal stromal tumors (GISTs) and is rarely
expressed in other soft tissue tumors, which, due to appearance, can be confusedwith GISTs. Reactivity for DOG-1 has been suggested to aid in the identification of
GISTs, including Platelet-Derived Growth Factor Receptor Alpha mutants that fail toexpress KIT antigen.

Desmin is recommended for the detection of specific antigens of interest in normal
and neoplastic tissues, as an adjunct to conventional histopathology using nonimmunologic histochemical stains.

DOG-1 is recommended for the detection of specific antigens of interest in normal
and neoplastic tissues, as an adjunct to conventional histopathology using nonimmunologic histochemical stains.
PRODUCT SPECIFIC INFORMATIONThe use of PBS-based diluents may result in increased background staining.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Dysferlin Antibodies

N

G

-

A

N

T

I

B

O

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Dystrophin Antibodies
A

Human skeletal muscle: immunohistochemical staining of HAMLET: HAMLET: clone
Ham1/7B6

B

Human skeletal muscle: immunohistochemical staining for Dystrophin. Note membranestaining of normal muscle fibers (A) and reduced and variable staining of revertant muscle
fibers (B). Dystrophin: clone 13H6

Ham1/7B6FORMAT

CODE

USAGE

US

EU

ROW*

Lyophilized 1 mL

NCL-HAMLETF;P(HIER)

IVD

IVD

IVD

DYSA (Rod Domain): clone 13H6

Ham3/17B2
FORMAT

CODE

USAGE

US

EU

ROW*

Lyophilized 1 mL

NCL-HAMLET-2

F;P(HIER)

IVD

IVD

IVD

FORMAT

CODE

USAGE

US

EU

ROW*

Lyophilized 1 mL

NCL-DYSAP(HIER)

RUO

RUO

RUO

DYSB (N-terminus): clone 34C5PATHOLOGY MENUFORMAT

CODE

USAGE

US

EU

ROW*

Lyophilized 1 mL

NCL-DYSBP(HIER)

RUO

RUO

RUO

DYS1 (Rod Domain): clone Dy4/6D3

MUSCLE PATHOLOGYANTIGEN BACKGROUND
Dysferlin is the protein product of the 2p13 gene that is defective in patientswith Limb-Girdle Muscular Dystrophy type 2B (LGMD2B) and Miyoshi Myopathy(MM). Dysferlin is normally localized to the muscle plasma membrane. In patientswith LGMD2B and MM, immunoreactivity to dysferlin is severely reduced or lost.
Patients with other neuromuscular conditions demonstrate normal labeling
patterns.

FORMAT

CODE

USAGE

US

EU

ROW*

Lyophilized 2.5 mL

NCL-DYS1

F

IVD

IVD

IVD

DYS2 (C-terminus) : clone Dy8/6C5
FORMAT

CODE

USAGE

US

EU

ROW*

Lyophilized 2.5 mL

NCL-DYS2

F

IVD

IVD

IVD

DYS3 (N-terminus) : clone Dy10/12B2

Dysferlin Antibodies are recommended for the detection of specific antigens
of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.
PRODUCT SPECIFIC INFORMATIONFORMAT

CODE

USAGE

US

EU

ROW*

Lyophilized 2.5 mL

NCL-DYS3

F

IVD

IVD

IVD

PATHOLOGY MENU

The use of the heat induced epitope retrieval (HIER) technique can enhance
staining in some cases.

MUSCLE PATHOLOGYANTIGEN BACKGROUND
Duchenne Muscular dystrophy (DMD) is the most common of the muscular
dystrophies resulting in progressive muscular wasting and death. Dystrophin is the
427kD protein product of the DMD gene located on the X chromosome at position
Xp21. Abnormalities in protein expression occur in patients with DMD/BMD
and dystrophin analysis may be used to distinguish these conditions from otherneuromuscular diseases. Severe Duchenne muscular dystrophy is associated witha marked dystrophin deficiency, whereas patients with the milder form of Becker
muscular dystrophy show less pronounced abnormalities of protein expression.
The immunolabeling patterns for DYS1, DYS2 and DYS3 are similar; however, theuse of all three antibodies is recommended to avoid the possibility of occasional
false negative results.
Dystrophin Antibodies are recommended for the detection of specific antigens
of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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E-Cadherin

EmerinInvasive breast carcinoma: immunohistochemical staining for E-Cadherin.
E-Cadherin: clone 36B5

Human skeletal muscle: immunohistochemical staining for Emerin. Note perinuclear stainingof all cell nuclei. Emerin: clone 4G5

36B5

4G5

FORMAT

CODE

USAGE

US

EU

ROW*

FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0387P(HIER)

IVD

IVD

IVD

Lyophilized 1 mL

NCL-EMERIN

F;P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-E-Cad

P(HIER)

IVD

IVD

IVD

S

PATHOLOGY MENUPATHOLOGY MENUMUSCLE PATHOLOGYBREAST PATHOLOGYANTIGEN BACKGROUNDANTIGEN BACKGROUND

Emery-Dreifuss muscular dystrophy (EDMD) is a late onset, X-linked, recessive
disorder characterized by slowly progressing contractures, wasting of skeletal
muscle and cardiomyopathy usually presented as heart block. Contractures areseen in the elbows, Achilles tendons and post cervical muscles with humeroperoneal distribution early in the course of the disease. The STA gene, at Xq28
locus, encodes a serine-rich 34kD protein, emerin, which is ubiquitous in tissues
and is found in highest concentration in skeletal and cardiac muscle. Emerin is
localized in the nuclear membrane of normal muscle cells and its deficiency plays
a crucial part in the pathology of EDMD.

E-cadherin is a Ca2+-dependent, transmembrane cell adhesion molecule. It plays
an important role in the growth, development and the intercellular adhesion ofepithelial cells. Most tumors have an abnormal architecture and any subsequentloss of adhesiveness is thought to be an important step in the development oflocal invasion. E-cadherin may have a role in neoplastic progression, particularly
as a suppressor of invasion. In prostate cancers, for example, the expression ofE-cadherin is reported to be reduced or absent in comparison with its expression
in normal prostate which is uniformly strong. Reduced expression or absenceof E-cadherin in addition to alpha, beta and gamma-catenin in primary breast
carcinomas has also been reported and these four proteins are associated with thedevelopment of metastases.

Emerin is recommended for the detection of specific antigens of interest in normal
and neoplastic tissues, as an adjunct to conventional histopathology using nonimmunologic histochemical stains.

E-Cadherin is recommended for the detection of specific antigens of interest in
normal and neoplastic tissues, as an adjunct to conventional histopathology using
non-immunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Epidermal Growth Factor Receptor

Epithelial Membrane Antigen

Human Placenta: immunohistochemical staining for Epidermal Growth Factor Receptor.
Epidermal Growth Factor Receptor: clone EGFR.113

Human breast cancer: immunohistochemical staining for Epithelial Membrane Antigen.
Epithelial Membrane Antigen: clone GP1.4

EGFR.113

GP1.4

S

FORMAT

CODE

USAGE

US

EU

ROW*

FORMAT

CODE

USAGE

US

EU

Liquid 1 mL

NCL-L-EGFR

P(HIER)

IVD

IVD

IVD

BOND 7 mL

PA0035P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-EMA

P

IVD

IVD

IVD/RUOPATHOLOGY MENULUNG PATHOLOGYROW*

PATHOLOGY MENU
TUMOR DIFFERENTIATIONANTIGEN BACKGROUNDANTIGEN BACKGROUND

Epidermal growth factor receptor (EGFR) is a transmembrane protein receptor of
170 kD with tyrosine kinase activity. Increased levels of EGFR are reported to belinked with malignant transformation of squamous cells, for example, in squamouscell carcinoma of the lung, head, neck, skin, cervix and esophagus. EGFR may also
play a role in the development and progression of hepatocellular carcinomas whererecurrence rates are higher in EGFR-positive cases. This correlation has similarly
been reported in colorectal cancers where EGFR, produced by tumor cells, plays
an important role in the invasiveness and proliferation of colorectal cancers. The
majority of published studies of EGFR expression in human breast cancer has
similarly shown an association with EGFR expression where it is inversely related
to estrogen receptor status.

Epithelial membrane antigen (EMA), also known as episialin, is reported to be
expressed in a variety of normal and neoplastic epithelia. It has been reported thatmarkers to CD45 (LCA) when used in conjunction with markers to EMA are usefulin labeling cells of lymphoid origin, whereas the combination of anti-cytokeratin
antibodies together with EMA is useful to characterize cells of epithelial
origin. EMA is also notably described to be expressed in a subset of Hodgkin’s
lymphomas.
Epithelial Membrane Antigen is recommended for the detection of specificantigens of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

Epidermal Growth Factor Receptor is recommended for the detection of specificantigens of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.
PRODUCT SPECIFIC INFORMATION
Clone EGFR.113 is raised to the extracellular domain of the EGFR molecule.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Estrogen Receptor
A

N

G

-

A

N

T

I

B

O

D

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S

EZH2 (Enhancer of Zeste Homolog 2(Drosophila))B

Left: Invasive ductal carcinoma (high expressor): intense nuclear staining in nearly 100% of
tumor cells. Right: Invasive ductal carcinoma (moderate expressor): immunohistochemical
staining for estrogen receptor. Estrogen Receptor: clone 6F11

T-Cell Lymphoma: immunohistochemical staining for EZH2 antigen. EZH2 (Enhancer of Zeste
Homolog 2 (Drosophila)): clone 6A10

6A10

6F11

FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0575P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-EZH2

P(HIER)

IVD

IVD

IVD

FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0151

P(HIER)

IVD

IVD

IVD

BOND 30 mL

PA0009P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-ER-6F11

P(HIER)

IVD

IVD

IVD

PATHOLOGY MENU

Liquid 2 mL

NCL-L-ER-6F11/2

P(HIER)

-

IVD

IVD

SPECIALIZEDPATHOLOGY MENUANTIGEN BACKGROUND

BREAST PATHOLOGY

Polycomb-group proteins (PcG) such as EZH2 (Enhancer of Zeste Homolog
2 (Drosophila)) form multimeric gene repressing complexes involved in axial
patterning, hematopoiesis and cell cycle regulation. PcG proteins ensure correct
embryonic development by expressing homeobox genes as well as contributing to
the regulation of lymphopoiesis.

ANTIGEN BACKGROUND
Estrogen receptor (ER) content of breast cancer tissue is an important parameterin the prediction of prognosis and response to endocrine therapy. The introductionof highly specific monoclonal antibodies to ER has allowed the determinationof receptor status of breast tumors to be carried out in routine histopathology
laboratories.

EZH2 (Enhancer of Zeste Homolog 2 (Drosophila)) is recommended for thedetection of specific antigens of interest in normal and neoplastic tissues, as an
adjunct to conventional histopathology using non-immunologic histochemical
stains.

Estrogen Receptor is recommended for the detection of specific antigens
of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

PRODUCT SPECIFIC INFORMATION
EZH2 stains optimally when used in TBS-based wash buffer and diluent systems.

PRODUCT SPECIFIC INFORMATION
Clone 6F11 is raised to the full length alpha form of the estrogen receptor
molecule.
Refer to the IFU for appropriate use instructions.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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B

O

D

Factor XIIIa(Blood Coagulation Factor XIIIa)

FascinHuman placenta: immunohistochemical staining of Factor XIIIa localized in the Hofbauer cellsof the placental villi. Factor XIIIa (Blood Coagulation Factor XIIIa): clone E980.1

Hodgkin’s lymphoma: immunohistochemical staining with Fascin: clone IM20

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0449P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-FXIIIa

P(HIER)

IVD

-

-

E

S

IM20

E980.1
FORMATI

FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0420P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-FASCINP(HIER); W

RUO

RUO

RUO

PATHOLOGY MENUPATHOLOGY MENUHEMATOPATHOLOGY

SPECIALIZEDANTIGEN BACKGROUNDANTIGEN BACKGROUND

Human fascin is a 55 to 58 kD actin-bundling protein, whose actin binding ability
is regulated by phosphorylation. In normal tissues the detection of fascin isreported to be predominantly restricted to dendritic cells, and in the thymus has
been observed only in medullary dendritic cells. In reactive nodes, interdigitating
reticulum cells of T cell zones, cells in subcapsular areas, and cells of the reticular
network express fascin. Variable expression is seen in follicular dendritic cells andendothelial cells. Lymphoid cells, myeloid cells and plasma cells do not express
fascin; however, in cases of Hodgkin’s disease, including nodular sclerosis, mixed
cellularity lymphocyte depletion and unclassified cases, most or all Reed Sternberg
cells are reported to be positive for fascin. Fascin expression may be induced by
Epstein-Barr virus (EBV) infection of B cells with the possibility that viral inductionof fascin in lymphoid or other cell types must also be considered in EBV-positive
cases.

Factor XIIIa, also known as fibrinoligase and fibrin-stabilizing factor, is the last
enzyme generated in the blood coagulation cascade. It is a Ca2+-dependenttransglutaminase or transamidating enzyme which forms intermolecular gammaglutamyl-epsilon-lysine crosslinks between fibrin molecules resulting in themechanical stabilization of the fibrin clot and its resistance to proteolysis. Factor
XIIIa may also function to stabilize cell surface molecules and membranes. Ca2+dependent trans-glutaminases with thiol active centers are widespread in animal
tissues and have been associated with cell proliferation, embryonic development
and growth through the proliferation of mammary stroma and epithelial elements.
Normal mammary stroma, like most collagenous connective tissue contains
resident populations of CD34 positive dendritic interstitial cells and scattered
Factor XIIIa positive collagen-associated dendrophages. Factor XIIIa has been
examined to determine its expression in normal and inflamed skin. Factor XIIIa
positive cells in human skin represent a specific population of bone marrow dermal
dendritic cells, distinct from Langerhans cells which share some features common
to mononuclear phagocytes. In benign skin conditions such as inflammatory
dermatoses, for example, atopic eczema and psoriasis, an increased number offactor XIIIa positive cells in the upper dermis, closely associated with lymphocytes,
has been described.

Fascin is recommended for the detection of specific antigens of interest in normal
and neoplastic tissues, as an adjunct to conventional histopathology using nonimmunologic histochemical stains.

Factor XIIIa (Blood Coagulation Factor XIIIa) is recommended for the detectionof specific antigens of interest in normal and neoplastic tissues, as an adjunct toconventional histopathology using non-immunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Folate Receptor Alpha

Galectin-3

Ovarian tumor: immunohistochemical staining for Folate Receptor Alpha.
Folate Receptor Alpha: clone BN3.2

Prostate carcinoma: immunohistochemical staining of Galectin-3. Galectin-3: clone 9C4

S

9C4

BN3.2
FORMAT

CODE

USAGE

US

EU

ROW*

Liquid 1 mL

NCL-L-FRalphaP(HIER)

IVD

IVD

IVD

FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0238P(HIER)

IVD

IVD

IVD

PATHOLOGY MENUPATHOLOGY MENUHEMATOPATHOLOGY

SPECIALIZEDANTIGEN BACKGROUNDANTIGEN BACKGROUND

Galectin-3 is a member of the beta-galactosidase-binding lectin family. It isinvolved in several biological events including binding to the basement membrane
glycoprotein laminin. Cell surface galectin-3 may be involved in homotypicalcell adhesion and is downregulated in colon cancer as the disease progresses.
This downregulation has also been examined in breast carcinoma with a similarcorrelation of expression reported. Downregulation of galectin-3 could be oneof the many events that enable cancer cells to interact with laminin to facilitate
invasion and metastasis and may indicate activation of the invasive phenotype invarious tumor types.

Folate is a basic component of cell metabolism and DNA synthesis and repair. It
is involved in essential one-carbon transfer reactions and is a vitamin required byboth normal and tumor cells. Folate entry into cells is facilitated via two different
systems: the reduced folate carrier, which utilizes a bidirectional anion-exchangemechanism, and the folate receptor system. Folate receptor alpha is a membranebound member of the folate receptor family, facilitating folate transport via
a mechanism termed potocytosis where the receptor is internalized and thenrecycled back to the cell membrane. Staining patterns are both membranousand cytoplasmic due to this mechanism. Members of the folate receptor family
share highly conserved sequences in the open reading frames, but differ in aminoacids in the 5’ untranslated regions and as a consequence can differ in function
and tissue expression. Folate receptor alpha expression is reported to be highly
restricted in normal tissues and only selectively overexpressed in a limited numberof epithelial malignancies.

Galectin-3 is recommended for the detection of specific antigens of interest in
normal and neoplastic tissues, as an adjunct to conventional histopathology using
non-immunologic histochemical stains.

Folate Receptor Alpha is recommended for the detection of specific antigens
of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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GastrinGemininNormal human stomach: immunohistochemical staining for Gastrin. Note: intense cytoplasmic
staining of neuroendocrine cells. Gastrin: Polyclonal

Human chronic lymphocytic leukemia: immunohistochemical staining for Geminin.
Geminin: clone EM6

Polyclonal

EM6

E

FORMAT

CODE

USAGE

US

EU

ROW*

FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0681

P

IVD

IVD

IVD

Liquid 1 mL

NCL-L-Geminin

P(HIER)

IVD

IVD

IVD

PATHOLOGY MENUPATHOLOGY MENUGASTROINTESTINAL PATHOLOGY

SPECIALIZEDS

ANTIGEN BACKGROUNDANTIGEN BACKGROUND

Gastrin, a polypeptide hormone, occurs naturally in three forms: gastrin-14,
gastrin-17 and gastrin-34. Both primary and secondary G cell hyperplasia arereported to be characterized by clustering of the immunoreactive cells whichsometimes project buds from the mucous glands.

Geminin is a protein of 209 amino acids thought to be involved in the controlof DNA replication via the interaction with Cdt1. Geminin is not found in the G1
phase of the cell cycle, but is first expressed in the G1 to S transition phase, withexpression levels rising through the rest of the cell cycle and levels reachinga maximum during mitosis. It has been proposed that geminin may be atumor suppressor protein. Geminin is reported to be expressed in proliferating
lymphocytes and epithelial cells, for example, germinal centers in tonsil as well as
in colon, spermatocytes, seminiferous tubules of the testes, within the basal layersof the squamous epithelium of the skin and breast. Geminin is reported to be
upregulated in cancers such as non-Hodgkin’s lymphoma, B cell lymphoma, breast
carcinoma and colon carcinoma.

Gastrin is recommended for the detection of specific antigens of interest in normal
and neoplastic tissues, as an adjunct to conventional histopathology using nonimmunologic histochemical stains.

Geminin is recommended for the detection of specific antigens of interest in
normal and neoplastic tissues, as an adjunct to conventional histopathology using
non-immunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Glial Fibrillary Acidic Protein

Glutathione S-Transferase (GST)
Antibody

Normal brain: immunohistochemical staining for Glial Fibrillary Acidic Protein.
Glial Fibrillary Acidic Protein: clone GA5

Human liver: immunohistochemical staining for GSTpi. Note staining of bile ducts.
Glutathione S-transferase pi: clone LW29

GA5

LW29

E

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FORMAT

CODE

USAGE

US

EU

ROW*

FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0026P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-GSTpi-438

P

IVD

-

-

Liquid 1 mL

NCL-L-GFAP-GA5

P(HIER)

IVD

IVD

IVD

PATHOLOGY MENUPATHOLOGY MENUSPECIALIZEDNEUROPATHOLOGYANTIGEN BACKGROUNDANTIGEN BACKGROUND

The glutathione S-transferases (GSTs) are a multigene family of isoenzymes whichcatalyze the conjugation of glutathione to electrophilic substrates. These enzymes
are involved in the detoxification of both endogenous and exogenous electrophiles
which can react with cellular components such as DNA. The modification of DNA
by reactive compounds can initiate carcinogenesis and the GSTs are believed toplay a role in neutralizing carcinogens. The cytosolic GST isoenzymes have beenclassified into four evolutionary classes; alpha, mu, pi and theta. These isoenzymes
are reported to be singly or multi-expressed in a variety of normal tissues, including
stomach, bowel, brain, heart, liver, pancreas, breast, kidney and skin at differinglevels. In gastric cancers, the levels of GSTalpha and pi are reported to differ
from normal gastric tissue with GSTalpha showing decreased levels and GSTpi
increased levels.

Glial fibrillary acidic protein (GFAP) is an intermediate filament protein of 52kD
reported to be expressed in glial cells, for example, astrocytes and ependymal
cells. In the peripheral nervous system, GFAP has been reported to be expressed in
Schwann cells, enteric glial cells and satellite cells of human sensory ganglia andin neoplastic tissues GFAP has been reported to be expressed in astrocytomas andependymomas.
Glial Fibrillary Acidic Protein is recommended for the detection of specific antigens
of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.
PRODUCT SPECIFIC INFORMATION

Glutathione S-Transferase (GST) Antibody is recommended for the detection of
specific antigens of interest in normal and neoplastic tissues, as an adjunct toconventional histopathology using non-immunologic histochemical stains.

The use of the heat induced epitope retrieval (HIER) technique can enhance
staining in some cases.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Granzyme B

Gross Cystic Disease Fluid Protein-15

Human tonsil: immunohistochemical staining for Granzyme B: clone 11F1

Invasive breast carcinoma: immunohistochemical staining for Gross Cystic Disease Fluid
Protien-15. Gross Cystic Disease Fluid Protein-15: clone 23A3

11F1
FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0291

P(HIER)

IVD

IVD

IVD

NCL-L-GRAN-B

P(HIER)

IVD

IVD

IVD/RUO

Liquid 1 mL

S

23A3

PATHOLOGY MENUFORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0708P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-GCDFP15

P(HIER)

IVD

IVD

IVD

PATHOLOGY MENUHEMATOPATHOLOGYBREAST PATHOLOGYANTIGEN BACKGROUNDANTIGEN BACKGROUND

Granzymes are neutral serine proteases which are stored in specialized lytic
granules of cytotoxic T lymphocytes (CTL) and in natural killer (NK) cells. These
CTL and NK cells are heavily involved in the elimination of neoplastic andvirally infected cells. Secretory granules containing perforin and granzymes are
instrumental in undertaking cytolytic activity. Granzyme B is understood to entera target cell through a perforin pore-formed channel to induce DNA fragmentation
and apoptosis. Granzyme B has also been described in neoplastic CTL and NK
cells.

Gross cystic disease of the breast is a benign premenopausal disorder in whichcysts are a predominant pathological lesion. These cysts appear to be formed
from excessive apocrine cystic secretions. This fluid is composed of several
glycoproteins including a unique 15 kD monomer protein, GCDFP15. It has beenreported that cytosolic analysis of normal tissue from all major organs has
demonstrated GCDFP15 in apocrine epithelia, lacrimal, ceruminous and Moll’s
glands and in numerous serous cells of the submandibular, tracheal, bronchial,sublingual and minor salivary glands. Cytosol from breast carcinoma lesions arereported to contain GCDFP15 at a wide range of concentrations. The concentrationis reported to be highest in more differentiated carcinomas and GCDFP15 shows
only a few positive individual epithelial cells within lobules and small ducts innormal breast. Expression has also been reported in fibroadenomas within areas of
apocrine metaplasia.

Granzyme B is recommended for the detection of specific antigens of interest in
normal and neoplastic tissues, as an adjunct to conventional histopathology using
non-immunologic histochemical stains.

Gross Cystic Disease Fluid Protein-15 is recommended for the detection of specificantigens of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Helicobacter pylori

Human Chorionic Gonadotrophin (beta)

Immunohistochemical staining for Helicobacter pylori: clone ULC3R

Human placenta: immunohistochemical staining with Human Chorionic Gonadotrophin (beta):
Polyclonal

Polyclonal
FORMAT

CODE

Liquid 7 mL

IHC5994-A

USAGE
-

US

EU

ROW*

ASR

-

-

US

EU

ROW*

ASR

IVD

IVD

Polyclonal

ULC3R
FORMAT

CODE

USAGE

Liquid 1 mL

NCL-L-Hpylori-

FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0014P(HIER)

IVD

IVD

IVD

PATHOLOGY MENUGYNEPATHOLOGYANTIGEN BACKGROUNDPATHOLOGY MENU

Human chorionic gonadotrophin (hCG) is a glycoprotein hormone produced bytrophoblastic cells of the placenta beginning 10 to 12 days after conception.
Maintenance of the fetus in the first trimester of pregnancy requires the productionof hCG, which binds to the corpus luteum of the ovary which is stimulated to
produce progesterone which in turn maintains the secretory endometrium. hCG is
composed of two subunits, alpha and beta. The alpha subunit of hCG is identicalto the subunit of luteinising hormone, thyroid stimulating hormone and follicle
stimulating hormone. The common alpha chain and the hormone-specific beta
chains have molecular weights of 14 kD and 17 kD, respectively. The hCG betasubunit is unique in the family of beta-containing glycoprotein hormones in thatit contains an extension of 29 amino acids at its COOH end. It is believed that the
C-terminal region of the HCG-beta subunit plays a role in the intracellular behaviorof the heterodimer.

GASTROINTESTINAL PATHOLOGYANALYTE SPECIFIC REAGENT
Analyte Specific Reagent. Analytical and performance characteristics are notestablished.

Human Chorionic Gonadotrophin (beta) is recommended for the detection of
specific antigens of interest in normal and neoplastic tissues, as an adjunct toconventional histopathology using non-immunologic histochemical stains.
PRODUCT SPECIFIC INFORMATIONHCGp was raised to the isolated beta-chain of human chorionic gonadotrophin
and reacts with placental trophoblasts. HCGp shows a slight cross-reaction withluteinising hormone and may, therefore, stain basophil cells in the pituitary.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Human Follicle Stimulating Hormone(beta 2) (HFSH)

Human Growth Hormone (HGH)

Human pituitary: immunohistochemical staining for HFSH. Note cytoplasmic staining of
gonadotrophic cells. Human Follicle Stimulating Hormone (beta 2): clone INN-hFSH-60

Human pituitary: immunohistochemical staining for HGH. Note cytoplasmic staining ofsomatotrophic cells. Human Growth Hormone: Polyclonal

INN-hFSH-60

Polyclonal

FORMAT

CODE

USAGE

US

EU

ROW*

FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0693P(ENZYME)

IVD

IVD

IVD

BOND 7 mL

PA0704

P

IVD

IVD

IVD

PATHOLOGY MENUPATHOLOGY MENU

HEAD, NECK AND ENDOCRINE

HEAD, NECK AND ENDOCRINEANTIGEN BACKGROUNDANTIGEN BACKGROUND

Follicle stimulating hormone (FSH) is a pituitary hormone of 35 kD which is
involved in the maturation of ovarian follicles and estrogen secretion in females. In
males, FSH stimulates the secretion of testosterone.

Growth hormone (GH), somatotropin, is the primary hormone responsible forregulating overall body growth and is also important in organic metabolism. It issynthesized by acidophilic or somatotropic cells of the anterior pituitary gland.
Human GH has a molecular weight of 22 kD.

Human Follicle Stimulating Hormone (beta 2) (HFSH) is recommended for thedetection of specific antigens of interest in normal and neoplastic tissues, as an
adjunct to conventional histopathology using non-immunologic histochemical
stains.

S

GH stimulates growth indirectly by promoting the liver’s production ofsomatomedins, which act directly on bone and soft tissue to cause growth. GH
exerts direct metabolic effects on the liver, adipose tissue and muscle. In general,
growth hormone enhances protein synthesis, conserves carbohydrates and uses
up fat stores.
Human Growth Hormone (HGH) is recommended for the detection of specificantigens of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Human Herpesvirus 8 (HHV8)

Immunoglobulin A

Human skin, Kaposi’s sarcoma: immunohistochemical staining for HHV8.
Human Herpesvirus 8: clone 13B10

Human appendix: immunohistochemical staining for Immunoglobulin A. Note the intense
staining of plasma cells and secreted Immunoglobulin A: clone N1CLA

13B10

N1CLA

S

FORMAT

CODE

USAGE

US

EU

ROW*

FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0050P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-IgA

P(HIER)

IVD

IVD

IVD/RUO

Liquid 1 mL

NCL-L-HHV8-LNA

P(HIER)

IVD

IVD

IVD

PATHOLOGY MENUPATHOLOGY MENUHEMATOPATHOLOGY

DERMATOPATHOLOGYANTIGEN BACKGROUNDANTIGEN BACKGROUND
Human herpesvirus type 8 (HHV8), is the proposed etiological agent of Kaposi’s
sarcoma (KS). It is reported that HHV8 has been demonstrated in KS tissues byimmunohistochemistry, in situ PCR and also in situ hybridization. HHV8 encodes
a latent nuclear antigen (LNA) which is the product of the viral gene ORF73. LNA
is capable of forming a complex with retinoblastoma susceptibility gene productwhich may be related to its oncogenic activity. HHV8 has been reported to be
expressed in multicentric Castleman’s disease (MCD) and in angioimmunoblastic
lymphadenopathies. The localization of HHV8 in subcapsular spindle cellproliferations, which is where early intranodal KS begins, and endothelial cells in
Castleman’s disease may explain the link between intranodal KS and MCD. In MCD,
HHV8 is reported to be expressed in mantle zone large immunoblastic B cells.

IgA is a member of the antibody class of the immunoglobulin superfamily. There
are several classes and subclasses (isotypes) of antibody, the antibody isotype
being defined by the immunoglobulin heavy chain present in the molecule. The
basic structure of an immunoglobulin molecule consists of two identical heavy
chains (gamma , mu, alpha , delta , epsilon) and two identical light chains, either
kappa or lambda. IgA contains the alpha -chain and may be present in a serum or
secretory form. In serum, 90% of IgA is monomeric, while in its secretory form itis the main immunoglobulin found in secretions including tears, saliva, intestinal
and bronchial mucous, sweat, colostrum, and secretions from the prostate andrespiratory epithelia, where it has the job of defending exposed external surfacesof the body against attack from micro organisms. Secretory IgA is synthesized
locally by plasma cells and dimerized intracellularly with a cysteine-rich J-chain.

Human Herpesvirus 8 (HHV8) is recommended for the detection of specificantigens of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

Immunoglobulin A is recommended for the detection of specific antigens
of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.
PRODUCT SPECIFIC INFORMATION
Clone N1CLA was developed to produce reduced background staining that is
associated with polyclonal antibodies on paraffin sections.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Immunoglobulin D

Immunoglobulin G

Mantle cell lymphoma: immunohistochemical staining for Immunoglobulin D.
Immunoglobulin D: clone DRN1C

Human tonsil: immunohistochemical staining for Immunoglobulin G. Note intense stainingof plasma cells, weaker staining of follicular dendritic cell network and some B cells.
Immunoglobulin G: clone RWP49

DRN1CFORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0061

P(HIER)

IVD

IVD

IVD

NCL-L-IgD

P(HIER)

IVD

IVD

IVD/RUO

Liquid 1 mL

S

RWP49

PATHOLOGY MENUFORMAT

CODE

USAGE

US

EU

BOND 7 mL

ROW*

PA0905P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-IgG

P(HIER)

IVD

IVD

IVD/RUOPATHOLOGY MENUHEMATOPATHOLOGYHEMATOPATHOLOGYANTIGEN BACKGROUNDANTIGEN BACKGROUND

IgD, together with IgM, are the major immunoglobulins expressed on the surface ofB cells where it seems they may operate as mutually interacting antigen receptors
for the control of lymphocyte activation and suppression. The greater susceptibilityof IgD to proteolysis in combination with antigen could well be implicated in sucha function.

The human immunoglobulins consist of two identical heavy chains (~50 kD) and
two identical light chains, which are linked together by disulphide bonds. The
light chains can be either kappa or lambda. The five immunoglobulins IgA, IgD,
IgE, IgG and IgM differ in their heavy chains, and IgA and IgM differ as they canoccur in polymeric forms. The heavy chain of IgG is named the gamma-chain.
In humans, IgG consists of four sub classes that differ only marginally in theiramino acid composition. Antibodies to IgG have been reported to be useful in theidentification of plasma cells, lymphoid cells containing IgG and classifying B cell
derived neoplasms. The normal B cell population is Polyclonal, expressing a rangeof different immunoglobulins. In contrast, the majority of B cell neoplasms arecharacterized by the proliferation of monoclonal cells expressing one type of lightchain, whereas more than one type of heavy chain can be expressed by the samecell.

Immunoglobulin D is recommended for the detection of specific antigens
of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

Immunoglobulin G is recommended for the detection of specific antigens
of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Immunoglobulin M

Inhibin Alpha

Human tonsil: immunohistochemical staining for Immunoglobulin M. Note intense stainingof plasma cells, weaker staining of follicular dendritic cell network and some B cells.
Immunoglobulin M: clone 8H6

Human testis: immunohistochemical staining for inhibin alpha showing cytoplasmic staining ofSertoli cells. Inhibin Alpha: clone R1

R1

8H6
FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0278P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-IgM

P(HIER)

IVD

IVD

IVD/RUOFORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0488P(HIER)

IVD

IVD

IVD

AMY82

PATHOLOGY MENUHEMATOPATHOLOGYFORMAT

CODE

USAGE

US

EU

ROW*

Liquid 1 mL

NCL-L-InhibinA

P(HIER)

IVD

IVD

IVD

PATHOLOGY MENUANTIGEN BACKGROUNDGYNEPATHOLOGY

IgM, together with IgD, is the major immunoglobulin expressed on the surfaceof B cells and normally constitutes about 10 per cent of serum immunoglobulin.
IgM antibody is prominent in early immune responses to most antigens andpredominates in certain antibody responses such as natural blood groupantibodies.

ANTIGEN BACKGROUND
Inhibins and activins are members of the transforming growth factor beta (TGFβ)family of cytokines. Inhibins are heterodimers consisting of a common α-subunit
linked to either a βA subunit ( α-βA, forming inhibin A) or a βB subunit ( α-βB,
forming inhibin B). Activins share the β-subunit with the inhibins and may behomo or heterodimers of β-subunits forming activin A (βA-βA), activin AB (βA-βB)
or activin B (βB-βB). The expression of the α-subunit, and therefore of inhibins
appears to be more restricted than that of the β-subunit, and therefore of activins.
Inhibins and activins play a role in the regulation of pituitary follicle stimulating
hormone (FSH) secretion. The actions of inhibins and activins are thought
to oppose one another, with inhibins suppressing FSH secretion and activins
stimulating FSH secretion. Inhibins are secreted by granulosa cells in female
follicles and Sertoli cells of the testis in the male. Inhibins are thought to have local
regulatory roles in a variety of tissues, in addition to the ovary, including the brain,
adrenal glands, bone marrow, fetus and placenta.

Immunoglobulin M is recommended for the detection of specific antigens
of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

Inhibin Alpha is recommended for the detection of specific antigens of interest in
normal and neoplastic tissues, as an adjunct to conventional histopathology using
non-immunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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InsulinInterleukin 6

Human pancreas: immunohistochemical staining for insulin-containing cells. Note intense
cytoplasmic staining. Insulin: clone 2D11-H5

Human colon: immunohistochemical staining for Interleukin 6. Note cytoplasmic staining of a
proportion of lymphoid cells. Interleukin 6: clone 10C12

2D11-H5

10C12

FORMAT

CODE

USAGE

US

EU

ROW*

FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0620

P

IVD

IVD

IVD

Liquid 1 mL

NCL-L-IL6

P

RUO

RUO

RUO

Liquid 1 mL

NCL-L-INSULIN

P

IVD

-

-

PATHOLOGY MENUPATHOLOGY MENUHEMATOPATHOLOGYHEAD, NECK AND ENDOCRINEANTIGEN BACKGROUNDANTIGEN BACKGROUND

IL-6 is a multifunctional cytokine that is secreted by both lymphoid and nonlymphoid cells. It plays a key role in immune responses, hematopoiesis and is
an important cytokine in cell proliferation and differentiation. It may also play animportant role as an autocrine growth factor in metastatic prostate cancer. IL-6 has
been reported to play a role in secretion or release of pituitary hormone in pituitaryhormone secreting cells and adenomas. In addition, IL-6 has been suggested tohave a trophic effect in nerve cells and to have a direct pathogenic role in CNS
disorders. There are an increasing number of reports that cytokines of the IL-6
family play an important regulatory role in heart physiology.

Insulin is a hormone secreted by the beta cells of the islets of Langerhans in thepancreas. It promotes glycogen storage, formation of triglycerides, and synthesisof protein and nucleic acids. Reports of immunocytochemical investigation reveal
the presence of insulin in the cytoplasm of certain islet tumors. However, in someinstances insulin-positive granules are sparse and form a margin against the cell
membrane.
Insulin is recommended for the detection of specific antigens of interest in normal
and neoplastic tissues, as an adjunct to conventional histopathology using nonimmunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Kappa Light Chain

Ki67 Antigen

Human tonsil: immunohistochemical staining with Kappa Light Chain: clone CH15

Diffuse large B cell lymphoma: immunohistochemical staining for Ki67. Ki67: clone MM1

CH15

MM1

S

FORMAT

CODE

USAGE

US

EU

ROW*

FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0606P(HIER)

IVD

IVD

IVD

BOND 7 mL

PA0118P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-KAP-581

P(ENZYME)

IVD

IVD

IVD

BOND 30 mL

PA0410P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-KI67-MM1

P(HIER)

IVD

IVD

IVD/RUOPATHOLOGY MENUHEMATOPATHOLOGYK2

ANTIGEN BACKGROUND
Immunoglobulins are polypeptides and comprise five major classes;
immunoglobulin G (IgG), IgA, IgM, IgD and IgE. Each immunoglobulin consistsof two identical heavy (H) chains and two identical light (L) chains.These arealso subdivided into sub classes, for example, IgG1. There are two classesof light chain; kappa and lambda. The ratio of kappa chains and light chainsvaries between Ig classes and sub classes, but is also species specific. In
humans, approximately 60% of light chains are kappa; however, in any particularimmunoglobulin molecule the light chain will be either kappa or lambda. B cells
contain either kappa or lambda mRNA.

FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0230P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-ACK02

P(HIER)

RUO

RUO

RUO

PATHOLOGY MENU
BREAST PATHOLOGYANTIGEN BACKGROUND
The Ki67 antigen is a nuclear protein which is expressed in all active parts of thecell cycle (G1, S, G2 and mitosis) but is absent in resting cells (G0). In contrast to
many other cell cycle-associated proteins, the Ki67 antigen is consistently absent
in quiescent cells and is not detectable during DNA repair processes. Thus, thepresence of Ki67 antigen is strictly associated with the cell cycle and confined to
the nucleus, suggesting an important role in the maintenance and/or regulation of
the cell division cycle.

Kappa Light Chain is recommended for the detection of specific antigens
of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

Ki67 Antigen is recommended for the detection of specific antigens of interest in
normal and neoplastic tissues, as an adjunct to conventional histopathology using
non-immunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Lambda Light Chain

Langerin

B cell chronic lymphocytic leukemia: immunohistochemical staining for Lambda Light Chain.
Lambda Light Chain: clone SHL53

Human skin: immunohistochemical staining for langerin. Langerin: clone 12D6

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0570P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-LAM-578

P(HIER)

IVD

IVD

IVD

E

S

12D6

SHL53
FORMATI

FORMAT

CODE

USAGE

US

EU

ROW*

Liquid 1 mL

NCL-L-LANGERINP(HIER)

IVD

IVD

IVD

PATHOLOGY MENUSPECIALIZEDPATHOLOGY MENUHEMATOPATHOLOGYANTIGEN BACKGROUND
Langerin is a type II transmembrane C-type lectin which has mannose-binding
specificity. It is a 40 kD protein restricted to Langerhans cells that is involvedin the internalization of cell surface material in these immature dendritic cells.
Dendritic cells are antigen-presenting cells that are required for initiation of a
specific T cell-driven immune response. These cells are found in non-lymphoidtissue as immature cells whose primary function is to capture antigen throughspecialized surface membrane endocytic structures or through macropinocytosis.
The dendritic cells migrate to secondary lymphoid tissue and mature into efficientantigen presenting cells. A part of the maturation process includes the loss ofadhesion receptors such as E-cadherin and the disappearance of Birbeck granules.
Although Langerin is reported to be located on the cell surface, it can be rapidlyinternalized following ligand capture into Birbeck granules. In fact, Langerin is apotent inducer of membrane superimposition and zippering leading to Birbeck
granule formation. In reports it has been suggested that the induction of Birbeck
granules is a consequence of the antigen-capture function of Langerin allowing
passage into these organelles and providing access to a non-classical antigen
processing pathway.

ANTIGEN BACKGROUND
The basic structure of an immunoglobulin molecule consists of two identicalheavy chains, either gamma, alpha, delta, or epsilon and two identical light chains,either kappa or lambda. Any heavy chain can associate with either light chain but
on any immunoglobulin molecule both light chains are of the same type. The ratioof kappa and lambda light chains varies between Ig classes and subclasses. In a
polyclonal population the ratio of kappa to lambda bearing B cells is approximately
2:1, with individual B cells thought to express kappa or lambda light chains,never both. The majority of kappa and lambda chains are bound to heavy chain
immunoglobulin, however in normal individuals low levels of free light chain
are present in serum. The occurrence of a mixture of kappa and lambda chain
expressing cells suggests a polyclonal population and a reactive or non-neoplastic
proliferation of B cells.
Lambda Light Chain is recommended for the detection of specific antigens
of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

Langerin is recommended for the detection of specific antigens of interest in
normal and neoplastic tissues, as an adjunct to conventional histopathology using
non-immunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Lysozyme (Muramidase)

Mammaglobin

Bone marrow: immunohistochemical staining of myeloid cells using Lysozyme: Polyclonal

Human ductal carcinoma of breast: immunohistochemical staining for Mammaglobin protein.
Mammaglobin: clone EP249

Polyclonal
FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0391

P(ENZYME)

IVD

IVD

IVD

EP249

PATHOLOGY MENUFORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0378P(HIER)

IVD

IVD

IVD

PATHOLOGY MENUHEMATOPATHOLOGYBREAST PATHOLOGYANTIGEN BACKGROUNDANTIGEN BACKGROUND

Intracellular muramidase, also known as lysozyme, has been reported to be
expressed in myeloid and monocytic cells, in leukocytes and in myelo-proliferative
disorders. Muramidase is also reported to be expressed in poorly differentiatedleukemic monoblasts.

Mammaglobin is a 93 kDa glycoprotein that belongs to the uteroglobin family ofproteins. It was first described in 1996 and found to be overexpressed in breast
cancer. Published reports suggest a role for mammaglobin in the diagnosis ofmetastatic breast carcinoma.

Lysozyme (Muramidase) is recommended for the detection of specific antigens
of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

Mammaglobin has been suggested as a useful marker for carcinomas of unknown
primary origin, with expression unaltered from the primary site. Additional
published data suggests a role for mammaglobin in the migration and invasion ofbreast cancer cells.
Mammaglobin is recommended for the detection of specific antigens of interest in
normal and neoplastic tissues, as an adjunct to conventional histopathology using
non-immunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Mast Cell Tryptase

Melan A

Human skin: immunohistochemical staining for Mast Cell Tryptase. Note cytoplasmic stainingof mast cells. Mast Cell Tryptase: clone 10D11

Human skin, melanoma: immunohistochemical staining for Melan A. Melan A: clone A103

A103

10D11
FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0019

P

IVD

IVD

IVD

Liquid 1 mL

NCL-L-MCTRYP-428

P

IVD

-

-

S

PATHOLOGY MENUFORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0233P(HIER)

IVD

IVD

IVD

BOND 30 mL

PA0044P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-MELANAP(HIER)

IVD

IVD

IVD/RUOPATHOLOGY MENUHEMATOPATHOLOGY

DERMATOPATHOLOGYANTIGEN BACKGROUNDANTIGEN BACKGROUND

Mast cells contain a number of preformed chemical mediators such as histamine,chymase, carboxypeptidase and proteolytic tryptase. A substantial quantity oftryptase is reported to be found in mast cells of skin and lung and suggests thisenzyme plays a major role in mast cell mediated events. In vitro studies indicate
tryptase can cleave C3 to form C3a anaphylatoxin, inactivate fibrinogen as a
coaguable substrate for thrombin and activate latent collagenase. Models ofallergenic disease in the skin, nose and lung have each indicated elevated tryptase
levels. Human mast cell tryptase has been reported to be implicated as a mediatorof inflammation. Mast cell degranulation in the gut causes mucus secretion,
mucosal edema, increased gut permeability and may be responsible for some ofthe symptoms and signs of inflammatory bowel disease.

Melan A, a product of the MART-1 gene, is a melanocyte differentiation marker
recognized by autologous cytotoxic T lymphocytes. Other melanoma-associatedmarkers recognized by autologous cytotoxic T cells are reported to include MAGE1, MAGE-3, tyrosinase, gp100, gp75, BAGE-1 and GAGE-1. The analysis of thesedifferent molecules and their expression in individual melanomas may be of help
in the study of their particular molecular roles in melanocyte differentiation andtumorigenesis.
Melan A is recommended for the detection of specific antigens of interest in
normal and neoplastic tissues, as an adjunct to conventional histopathology using
non-immunologic histochemical stains.

Mast Cell Tryptase is recommended for the detection of specific antigens
of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Melanoma Marker (HMB45)

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Merosin Laminin Alpha 2 ChainA

Human skin, melanoma: immunohistochemical staining for HMB45. Melanoma Marker(HMB45): clone HMB45

B

Human skeletal muscle: immunohistochemical staining for Merosin. Note membranestaining of normal muscle fibers (A) and absence of staining of muscle fibers (B).
Frozen sections. Photographs supplied courtesy of Dr Louise V B Anderson.
Merosin Laminin Alpha 2 Chain: clone Mer3/22B2

HMB45
FORMAT

CODE

USAGE

US

EU

ROW*

Mer3/22B2

BOND 7 mL

PA0027P(ENZYME)

IVD

IVD

IVD

FORMAT

CODE

USAGE

US

EU

ROW*

BOND 30 mL

PA0625P(ENZYME)

IVD

IVD

IVD

Lyophilized 1 mL

NCL-MEROSIN

F

IVD

IVD

IVD

Liquid 1 mL

NCL-L-HMB45

P(ENZYME)

IVD

IVD

IVD

PATHOLOGY MENUMUSCLE PATHOLOGYPATHOLOGY MENU
DERMATOPATHOLOGYANTIGEN BACKGROUND
The muscle-specific form of laminin, merosin, is composed of three chains: alpha2, beta 1 and gamma 1.

ANTIGEN BACKGROUND
The HMB45 antigen has also been identified in retinal pigment epithelium (RPE)
but is reported to be reactive only with the transient prenatal and infantile RPE.
No reaction is reported to be observed with intradermal nevi and normal adultmelanocytes and non-melanocytic cells.

Mutations in the chromosome 6 encoded gene for the laminin alpha 2 chain ofmerosin are responsible for a form of congenital muscular dystrophy (CMD).
Merosin-negative CMD is characterized by a severe clinical phenotype and isassociated with white matter changes on brain imaging.

Tumor cells of epithelial, lymphoid, glial and mesenchymal origin are reported tobe negative. This clone is well described in the literature. It is indicated to label
an intracytoplasmic antigen in the majority of melanomas and other tumors
demonstrating melanoma/melanocytic differentiation.

Merosin Laminin Alpha 2 Chain is recommended for the detection of specificantigens of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

Melanoma Marker (HMB45) is recommended for the detection of specific antigens
of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Mesothelin

Microphthalmia Transcription Factor(MITF)

Human mesothelioma: immunohistochemical staining for Mesothelin. Mesothelin: clone 5B2

Human malignant melanoma: immunohistochemical staining for Microphthalmia Transcription
Factor. Microphthalmia Transcription Factor: clone 34CA5

5B2
FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0373P(HIER)

IVD

IVD

IVD

NCL-L-MESO

P(HIER)

IVD

IVD

IVD

Liquid 1 mL

34CA5
FORMAT

CODE

USAGE

US

EU

ROW*

Liquid 1 mL

NCL-L-MITF

F;P(HIER)

RUO

RUO

RUO

PATHOLOGY MENUPATHOLOGY MENU

DERMATOPATHOLOGYLUNG PATHOLOGYANTIGEN BACKGROUNDANTIGEN BACKGROUND

Microphthalmia transcription factor (MITF) gene product, a nuclear transcription
factor of the basic-helix-loop-helix type, is thought to play a role in the regulationof genes encoding the enzymes necessary for melanogenesis. These include
tyrosinase, TRP-1 and TRP-2. MITF is critical for the embryonic development
and postnatal viability of melanocytes. The melanocyte-specific isoform of
microphthalmia transcription factor MITF-M, is reported to be expressed in normal
and malignant melanocytes. The other isoforms, MITF-A, MITF-C and MITF-H, differ
structurally at the N-terminus from MITF-M.

Mesothelin is a glycosyl-phosphatidylinositol-linked (GPI) glycoprotein of 40kD
present on the surface of mesothelial cells, mesotheliomas, epithelial ovariancancers and some squamous cell carcinomas. It is synthesized as a 69 kD
precursor which is enzymatically processed into an N-terminal secreted formof 30 kD and the GPI-linked membrane-bound form of 40 kD. The secreted form
is identical to the megakaryocyte potentiating factor, but it is the GPI-linked
membrane-bound form which has generated interest. Mesothelin is abundantly
expressed in the kidney and in occasional epithelial cells of the trachea, tonsil
and fallopian tube. The function of mesothelin is unclear but it may have a role incellular adhesion. Mesothelin is reported to be abundant in the normal mesothelial
cells from which malignant mesotheliomas and ovarian cystadenocarcinomas arederived.

PRODUCT SPECIFIC INFORMATION
Clone 34CA5 is reported to be reactive with the MITF-M isoform.

Mesothelin is recommended for the detection of specific antigens of interest in
normal and neoplastic tissues, as an adjunct to conventional histopathology using
non-immunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Mismatch Repair Protein (MLH1)

Mismatch Repair Protein (MSH2)

Immunohistochemical staining for mismatch repair protein (MLH1). Mismatch Repair Protein(MLH1): clone ES05.

Immunohistochemical staining for mismatch repair protein (MSH2). Mismatch Repair Protein(MSH2): clone 79H11.

ES05

79H11

FORMAT

CODE

USAGE

US

EU

ROW*

FORMAT

CODE

USAGE

US

EU

BOND 7 mL

PA0988P(HIER)

IVD

IVD

-

BOND 7 mL

PA0989P(HIER)

IVD

IVD

-

Liquid 1 mL

NCL-L-MLH1

P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-MSH2-612

P(HIER)

IVD

IVD

IVD

ES05 (Previous Formulation)

ROW*

25D12

FORMAT

CODE

USAGE

US

EU

ROW*

FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0610P(HIER)

IVD

IVD

IVD

BOND 7 mL

PA0048P(HIER)

IVD

IVD

IVD

PATHOLOGY MENUPATHOLOGY MENUGASTROINTESTINAL PATHOLOGYGASTROINTESTINAL PATHOLOGYANTIGEN BACKGROUNDANTIGEN BACKGROUND

Mismatch repair gene hMLH1 is a ubiquitous gene encoding the mismatch repair
protein (MMR) MutL protein homolog 1 (MLH1). MLH1 functions by repairing
mutations occurring during DNA replication, in normal proliferating cells.

Mismatch repair gene MutS Homolog 2 is a ubiquitous gene encoding themismatch repair protein (MMR) MutS protein homolog 2 (MSH2). MSH2 functions
by repairing mutations occurring during DNA replication, in normal proliferating
cells.

Mismatch Repair Protein (MLH1) is recommended for the detection of specificantigens of interest in normal and neoplastic tissue, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

Mismatch Repair Protein (MSH2) is recommended for the detection of specificantigens of interest in normal and neoplastic tissue, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

PRODUCT SPECIFIC INFORMATIONThe use of the heat induced epitope retrieval (HIER) technique can enhance
staining in some cases. Any changes to the recommendations should be validated
by the end user.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Mismatch Repair Protein (MSH6)

Mismatch Repair Protein (PMS2)

Immunohistochemical staining for mismatch repair protein (MSH6). Mismatch Repair Protein(MSH6): clone EP49.

Immunohistochemical staining for mismatch repair protein (PMS2). Mismatch Repair Protein(PMS2): clone EP51.

EP49

EP51

FORMAT

CODE

USAGE

US

EU

ROW*

FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0990P(HIER)

IVD

IVD

-

BOND 7 mL

PA0991

P(HIER)

IVD

IVD

-

PU29

M0R4G

FORMAT

CODE

USAGE

US

EU

ROW*

FORMAT

CODE

USAGE

US

EU

ROW*

Liquid 1 mL

NCL-L-MSH6

P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-PMS2

P(HIER)

IVD

IVD

IVD

PATHOLOGY MENUPATHOLOGY MENUGASTROINTESTINAL PATHOLOGYGASTROINTESTINAL PATHOLOGYANTIGEN BACKGROUNDANTIGEN BACKGROUND

Mismatch repair gene MutS Homolog 6 is a ubiquitous gene encoding themismatch repair protein (MMR) MutS protein homolog 6 (MSH6). MSH6 functions
by repairing mutations occurring during DNA replication, in normal proliferating
cells.

Mismatch repair gene Postmeiotic segregation Increased 2, also known as
PMS1 Homolog 2, is a ubiquitous gene encoding the mismatch repair protein(MMR) PMS1 protein homolog 2 (PMS2). PMS2 functions by repairing mutations
occurring during DNA replication, in normal proliferating cells.

Mismatch Repair Protein (MSH6) is recommended for the detection of specificantigens of interest in normal and neoplastic tissue, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

Mismatch Repair Protein (PMS2) is recommended for the detection of specificantigens of interest in normal and neoplastic tissue, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

PRODUCT SPECIFIC INFORMATIONThe use of PBS-based diluents may result in increased background staining.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Muc-1 Glycoprotein

Muc-2 Glycoprotein

Human endometrium: immunohistochemical staining for Muc-1.
Muc-1 Glycoprotein: clone Ma695

Human colon: immunohistochemical staining for Muc-2 Glycoprotein: clone Ccp58

E

S

Ccp58

Ma695
FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0051

P(HIER)

IVD

IVD

IVD

FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0155P(HIER)

IVD

IVD

IVD

PATHOLOGY MENUPATHOLOGY MENUGASTROINTESTINAL PATHOLOGYGASTROINTESTINAL PATHOLOGYANTIGEN BACKGROUNDANTIGEN BACKGROUND

Mucins are heavily glycosylated glycoproteins which constitute the major
components of mucus that covers the surface of epithelial tissues. Nine distinct
epithelial mucin genes (Muc-1, 2, 3, 4, 5AC, 5B, 6, 7 and 8) have been identified.
Various immunohistochemical and in situ hybridization studies have shown thatthese mucins are differentially expressed in epithelia with cell-type specificity. The
normal gastric mucosa shows cell-type specific expression of Muc-1, Muc-5AC
and Muc-6 glycoproteins with the first two mucins found in superficial epitheliumand Muc-6 glycoprotein in the deep glands. Muc-1 and Muc-5AC glycoproteinsare expressed in many epithelia but Muc-6 glycoprotein is mainly expressed in
gastric mucosa. In addition, Muc-2 glycoprotein is not expressed in normal gastricmucosa.

Mucins are heavily glycosylated glycoproteins which constitute the major
components of mucus that covers the surface of epithelial tissues. Nine distinct
epithelial mucin genes (Muc-1, 2, 3, 4, 5AC, 5B, 6, 7 and 8) have been identified.
Various immunohistochemical and in situ hybridization studies have shown thatthese mucins are differentially expressed in epithelia with cell-type specificity. The
normal gastric mucosa shows cell-type specific expression of Muc-1, Muc-5AC
and Muc-6 glycoproteins with the first two mucins found in superficial epitheliumand Muc-6 glycoprotein in the deep glands. Muc-1 and Muc-5AC glycoproteinsare expressed in many epithelia but Muc-6 glycoprotein is mainly expressed in
gastric mucosa. In addition, Muc-2 glycoprotein is not expressed in normal gastricmucosa.

Muc-2 Glycoprotein is recommended for the detection of specific antigens
of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

Muc-1 Glycoprotein is recommended for the detection of specific antigens
of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Muc-5AC Glycoprotein

Muc-6 Glycoprotein

Human stomach: immunohistochemical staining for Muc- 5AC.
Muc-5AC Glycoprotein: clone CLH2

Human stomach: immunohistochemical staining for Muc-6. Muc-6 Glycoprotein: clone CLH5

S

CLH5

CLH2
FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0052P(HIER)

IVD

IVD

IVD

FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0053P(HIER)

IVD

IVD

IVD

PATHOLOGY MENUPATHOLOGY MENUGASTROINTESTINAL PATHOLOGYGASTROINTESTINAL PATHOLOGYANTIGEN BACKGROUNDANTIGEN BACKGROUND

Mucins are heavily glycosylated glycoproteins which constitute the major
components of mucus that covers the surface of epithelial tissues. Nine distinct
epithelial mucin genes (Muc-1, 2, 3, 4, 5AC, 5B, 6, 7 and 8) have been identified.
Various immunohistochemical and in situ hybridization studies have shown thatthese mucins are differentially expressed in epithelia with cell-type specificity. The
normal gastric mucosa shows cell-type specific expression of Muc-1, Muc-5AC
and Muc-6 glycoproteins with the first two mucins found in superficial epitheliumand Muc-6 glycoprotein in the deep glands. Muc-1 and Muc-5AC glycoproteinsare expressed in many epithelia but Muc-6 glycoprotein is mainly expressed in
gastric mucosa. In addition, Muc-2 glycoprotein is not expressed in normal gastricmucosa.

Mucins are heavily glycosylated glycoproteins which constitute the major
components of mucus that covers the surface of epithelial tissues. Nine distinct
epithelial mucin genes (Muc-1, 2, 3, 4, 5AC, 5B, 6, 7 and 8) have been identified.
Various immunohistochemical and in situ hybridization studies have shown thatthese mucins are differentially expressed in epithelia with cell-type specificity. The
normal gastric mucosa shows cell-type specific expression of Muc-1, Muc-5AC
and Muc-6 glycoproteins with the first two mucins found in superficial epitheliumand Muc-6 glycoprotein in the deep glands. Muc-1 and Muc-5AC glycoproteinsare expressed in many epithelia but Muc-6 glycoprotein is mainly expressed in
gastric mucosa. In addition, Muc-2 glycoprotein is not expressed in normal gastricmucosa.

Muc-6 Glycoprotein is recommended for the detection of specific antigens
of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

Muc-5AC Glycoprotein is recommended for the detection of specific antigens
of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Multiple Myeloma Oncogene 1 (MUM-1)

Muscle Specific Actin

Human tonsil: immunohistochemical staining for MUM-1.
Multiple Myeloma Oncogene 1: clone EAU32

Human leiomyosarcoma: immunohistochemical staining for Muscle Specific Actin.
Muscle Specific Actin: clone HHF35

EAU32

HHF35

E

S

FORMAT

CODE

USAGE

US

EU

ROW*

FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0129P(HIER)

IVD

IVD

IVD

BOND 7 mL

PA0258

P

IVD

IVD

IVD

Liquid 1 mL

NCL-L-MUM1

P(HIER)

IVD

IVD

IVD/RUO

Liquid 1 mL

NCL-L-MSA

P(ENZYME)

IVD

-

-

PATHOLOGY MENUSC28

HEMATOPATHOLOGYFORMAT

CODE

USAGE

US

EU

ROW*

Liquid 1 mL

NCL-L-MSA-594

P(HIER)

IVD

IVD

IVD

ANTIGEN BACKGROUNDPATHOLOGY MENUThe MUM-1 (multiple myeloma oncogene 1) gene was originally identified becauseof its involvement in the t(6:14) translocation observed in multiple myeloma,
which causes the juxtaposition of the MUM-1 gene to the Ig heavy chain locus.
MUM-1 is expressed in late plasma cell directed stages of B cell differentiation andin activated T cells, suggesting that MUM-1 may serve as a marker for lymphohemopoietic neoplasms derived from these cells. The morphologic spectrum of
MUM-1 expressing cells has been found to range from that of a centrocyte to thatof a plasmablast/plasma cell. Consequently the histogenic value of MUM-1 may be
to provide a marker to aid in the identification of the transition from BCL-6 positive(germinal center B cells) to CD138 positive (immunoblasts and plasma cells).

MUSCLE PATHOLOGYANTIGEN BACKGROUND
Muscle specific actin (MSA) is a highly conserved, ubiquitous protein found inmuscle and some non-muscle cells. Actins can be divided into three subsets, alphaactins found in muscle tissue cells, beta and gamma actins found in non-muscle
cells and a small subset of gamma actins also found in muscle tissue cells. In
normal tissues, expression is found in striated fibers of skeletal muscle, smoothmuscle in arteries, veins and pericytes of smaller arteries, muscle in bowel,
myometrium of the uterus, prostatic stroma, capsule cells of liver, kidney, lymph
node and spleen, the myoepithelial layers of mammary ducts and glands, eccrine
sweat glands and salivary glands. Expression is not found in epithelial cells,
lymphoid cells, macrophages, connective tissue and neuronal cells. In neoplastic
tissues, expression can be found in soft tissue tumors with muscle differentiation,for example, leiomyomas, leiomyosarcomas and rhabdomyosarcomas of varying
subtypes. Non-muscle sarcomas, carcinomas, melanomas and lymphomas do not
express muscle specific actin.

Multiple Myeloma Oncogene 1 (MUM-1) is recommended for the detection of
specific antigens of interest in normal and neoplastic tissues, as an adjunct toconventional histopathology using non-immunologic histochemical stains.

Muscle Specific Actin is recommended for the detection of specific antigens
of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Myeloperoxidase

MyoD1 (Rhabdomyosarcoma Marker)

Human bone marrow, granulocytic sarcoma: immunohistochemical staining for
myeloperoxidase. Myeloperoxidase: clone 59A5

Human rhabdomyosarcoma: immunohistochemical staining for MyoD1 protein.
MyoD1: clone 5.8A

59A5

5.8A

S

FORMAT

CODE

USAGE

US

EU

ROW*

FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0491

P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-MyoD1

P(HIER)

IVD--

Liquid 1 mL

NCL-L-MYELO

P

IVD

-

-

PATHOLOGY MENUPATHOLOGY MENUMUSCLE PATHOLOGYHEMATOPATHOLOGYANTIGEN BACKGROUNDANTIGEN BACKGROUND

The murine MyoD1 gene encodes a phosphoprotein of 45 kD, the function of which
may include the commitment, differentiation and maintenance of the myogenic
lineage. MyoD1 is not expressed in normal adult tissue but is reported to be highly
expressed in rhabdomyosarcomas.

Myeloperoxidase is a lysosomal enzyme found in cells of the myeloid series whichmetabolizes most of the hydrogen peroxide generated by activated phagocytes.
It is a major constituent of azurophilic cytoplasmic granules that uses hydrogen
peroxide to oxidize a variety of aromatic compounds and chloride ions tohypochlorous acid (HOCI), a strong oxidant. HOCI is the most bacteriocidal oxidant
known to be produced by neutrophils. HOCI reacts with proteins to form cytotoxic
chloramines. Myeloperoxidase is reported to be a major component in all myeloid
cells, including mature granulocytes and is a superior marker to myeloperoxidase
mRNA, whose level decreases with the maturation of the cell and is not detectablefrom the myelocyte stage onwards. Myeloperoxidase is reported to be expressed inneutrophil granulocytes and monocytes in blood, in precursors of granulocytes inthe bone marrow and in Kupffer cells of the liver.

MyoD1 (Rhabdomyosarcoma Marker) is recommended for the detection of specificantigens of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.
PRODUCT SPECIFIC INFORMATION
MyoD1 recognizes an epitope near the C-terminus of the MyoD1 protein (aminoacids 180 to 189).

Myeloperoxidase is recommended for the detection of specific antigens of interestin normal and neoplastic tissues, as an adjunct to conventional histopathology
using non-immunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Myogenin (Myf-4)

Myoglobin

Human rhabdomyosarcoma: immunohistochemical staining for Myf-4 protein.
Myogenin (Myf-4): clone LO26

Human rhabdomyosarcoma: immunohistochemical staining for myoglobin.
Myoglobin: clone MYO18

LO26

MYO18

I

E

FORMAT

CODE

USAGE

US

EU

ROW*

FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0226P(HIER)

IVD

IVD

IVD

BOND 7 mL

PA0727P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-Myf-4

P(HIER)

IVD

IVD

IVD

S

PATHOLOGY MENUPATHOLOGY MENUMUSCLE PATHOLOGYMUSCLE PATHOLOGYANTIGEN BACKGROUNDANTIGEN BACKGROUND

Myoglobin is a cytoplasmic, single chain polypeptide of 153 amino acids that
contains a single heme group. Myoglobin is reported to be expressed in skeletaland cardiac muscle but not in smooth muscle and functions as an oxygen
transporting pigment.

Rhabdomyosarcomas are a class of myoblast-derived soft tissue sarcomas thatusually express a number of muscle-specific genes and primarily affect children
and young adults. Differentiation of myogenic cells is controlled by a set of
regulatory genes including MyoD1, myogenin, Myf-5 and Myf-6. Myf-4 is the humanhomolog of myogenin. Its gene product, together with that of Myf-3, accumulates
in the nucleus of differentiated cells.

Myoglobin is recommended for the detection of specific antigens of interest in
normal and neoplastic tissues, as an adjunct to conventional histopathology using
non-immunologic histochemical stains.

Myogenin (Myf-4) is recommended for the detection of specific antigens of interestin normal and neoplastic tissues, as an adjunct to conventional histopathology
using non-immunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Myosin Heavy Chain Antibodies

N

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MyotilinA

Human prostate: immunohistochemical staining for myosin heavy chain. Note intense stainingof muscle fibers. Myosin Heavy Chain (smooth muscle): clone S131

Human skeletal muscle: immunohistochemical staining for Myotilin. Note sarcoplasmic
staining of normal muscle fibers (A) and presence of protein aggregates (B).
Myotilin: clone RSO34

Smooth muscle: clone S131
FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0493P(HIER)

IVD

IVD

IVD

RSO34

Developmental: clone RNMy2/9D2FORMAT

CODE

USAGE

US

EU

ROW*

Lyophilized 1 mL

NCL-MHCd

F

RUO

RUO

RUO

B

FORMAT

CODE

USAGE

US

EU

ROW*

Lyophilized 1 mL

NCL-MYOTILIN

F;P(HIER)

RUO

RUO

RUO

PATHOLOGY MENUMUSCLE PATHOLOGYANTIGEN BACKGROUND

Fast: clone WB-MHCf
FORMAT

CODE

USAGE

US

EU

ROW*

Lyophilized 1 mL

NCL-MHCf

F

RUO

RUO

RUO

The myotilin gene on chromosome 5q31 encodes a 498 amino acid polypeptide
with a molecular weight of 57kD. Myotilin is a structural protein of sarcomeric Z
discs and sarcolemma in human skeletal and cardiac muscle. It is homologous
to palladin and titin in the two C-terminal lg-domains and also to palladin in its
unique serine-rich N-terminal region. Myotilin interacts with alpha-actinin, actin
and gamma-filamin. Mutations in the myotilin gene are associated with limbgirdle muscular dystrophy 1 A (LGMD1A) and one form of Myofibrillar Myopathy.
It is highly conserved between human and mouse with its expression being morewidespread in the embryo than in the adult. Expression of myotilin has beenreported in adult skeletal and cardiac muscle with variable expression reported
in the peripheral nervous system, lung, liver and kidney. NCL-MYOTILIN will be ofuse in studies to determine the expression of myotilin in normal and pathologicaltissues.

Neonatal: clone WB-MHCn
FORMAT

CODE

USAGE

US

EU

ROW*

Lyophilized 1 mL

NCL-MHCn

F

RUO

RUO

RUO

Slow: clone WB-MHCs
FORMAT

CODE

USAGE

US

EU

ROW*

Lyophilized 1 mL

NCL-MHCs

F

RUO

RUO

RUO

PATHOLOGY MENUMUSCLE PATHOLOGYANTIGEN BACKGROUND
Myosin is a contractile muscle specific protein composed of two heavy and four
light chains. The myosin heavy chain has many isoforms which are specific fordifferent muscles or fiber types, some of which are developmentally regulated.
The range of myosin heavy chain antibodies may prove useful for investigating
development of intrafusal and extrafusal muscle fibers and the course of muscle
fiber regeneration. At the ultrastructural level, antibodies can reveal architecturaldetails of the myofilament as well as the cytoplasmic and membrane sites of new
myosin integration.
Myosin Heavy Chain Antibodies are recommended for the detection of specificantigens of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Napsin A

N-Cadherin

Human lung: immunohistochemical staining for Napsin A. Note cytoplasmic staining ofpneumocytes and alveolar macrophages. Napsin A: clone IP64

Human testis: immunohistochemical staining for N-Cadherin. Note cytoplasmic and membranestaining of Sertoli cells. N-Cadherin: clone IAR06

IP64

IAR06

FORMAT

CODE

USAGE

US

EU

ROW*

FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0064P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-N-CAD

P(HIER)

IVD

IVD

IVD/RUO

Liquid 1 mL

NCL-L-Napsin A

P(HIER)

IVD

IVD

IVD

PATHOLOGY MENUPATHOLOGY MENUSPECIALIZEDLUNG PATHOLOGYANTIGEN BACKGROUNDANTIGEN BACKGROUND

N-Cadherin is a member of the cadherin family of calcium dependent cell adhesion
molecules. The classical cadherins include the E, N, R, P and VE-Cadherins which
are believed to be expressed in a tissue specific manner. The classical cadherins
have a characteristic structure comprising an extracellular calcium-binding domain,
consisting of five repeats, a transmembrane domain and a highly conserved
cytoplasmic domain, which mediates interactions with cytoskeletal components ofthe cell via interactions with intracellular proteins including the catenins. Cadherins
play an important role in cell-cell adhesion, and are implicated in segregation andaggregation of tissues during development. N-Cadherin is reported to be expressedin various cell types including neural, myocardial and mesenchymal cells.

Napsin A has a specific function in normal alveolar epithelium and is proposed toplay a role in the proteolytic processing of surfactant precursors.
Napsin A is reported to be predominantly expressed in lamellar bodies of type
II pneumocytes, secondary lysosomes of alveolar macrophages, respiratory
epithelium of terminal and respiratory bronchioles, plasma cells, within a subset oflymphocytes in normal lung, as well as in epithelial cells of renal tubules in normal
kidney and is weakly expressed in normal spleen.
Studies have reported that Napsin A is expressed in 90% of primary lungadenocarcinomas.

N-Cadherin is recommended for the detection of specific antigens of interest in
normal and neoplastic tissues, as an adjunct to conventional histopathology using
non-immunologic histochemical stains.

Napsin A is recommended for the detection of specific antigens of interest in
normal and neoplastic tissues, as an adjunct to conventional histopathology using
non-immunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Negative Control (Mouse)

Negative Control (Rabbit)

Human tonsil: immunohistochemical staining with BOND Ready-to-Use Negative Control(Mouse) using BOND Polymer Refine Detection. Negative Control (Mouse): clone MOPC-21

Human bowel: immunohistochemical staining with BOND Ready-to-Use Negative Control(Rabbit) using BOND Polymer Refine Detection. Negative Control

MOPC-21-

FORMAT

CODE

USAGE

US

EU

ROW*

FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0996

P

IVD

IVD

IVD

BOND 7 mL

PA0777

P

IVD

IVD

IVD

ANTIGEN BACKGROUNDANTIGEN BACKGROUND

In some tissues, non-specific binding may occur, especially in neoplastic or
necrotic tissue.

In some tissues, non-specific binding may occur, especially in neoplastic or
necrotic tissue.

Negative Control (Mouse) is recommended for the detection of specific antigens
of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

Negative Control (Rabbit) is recommended for the detection of specific antigens
of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

PRODUCT SPECIFIC INFORMATIONPRODUCT SPECIFIC INFORMATIONThe use of Negative Control (Mouse) antibody is recommended to aid in theidentification of cells, tissues or tissue components, which may non-specificallybind mouse antibodies and will help with interpretation of specific staining at the
antigenic site.

The use of Negative Control (Rabbit) antibody is recommended to aid in theidentification of cells, tissues or tissue components, which may non-specificallybind mouse antibodies and will help with interpretation of specific staining at the
antigenic site.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Neurofilament 200kD

Neuron Specific Enolase

Human cerebellum: immunohistochemical staining for Neurofilament 200kD. Note cytoplasmic
staining of neurons and their axons. Neurofilament 200kD: clone N52.1.7

Human large bowel: immunohistochemical staining of Neuron Specific Enolase (NSE). Notethe staining in the neuronal elements and the ganglia of the longitudinal and circular smoothmuscle. Neuron Specific Enolase: clone 22C9

N52.1.7
FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0371

P(HIER)

IVD

IVD

IVD

NCL-L-NF200-N52

P(HIER)

IVD

IVD

IVD

Liquid 1 mL

S

22C9
FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0435P(HIER)

IVD

IVD

IVD

PATHOLOGY MENUPATHOLOGY MENUNEUROPATHOLOGYNEUROPATHOLOGYANTIGEN BACKGROUNDANTIGEN BACKGROUND

Enolase is a glycolytic enzyme catalyzing the reaction pathway between
2-phosphoglycerate and phosphoenol pyruvate. In mammals, enolase molecules
are dimers composed of three distinct subunits (alpha, beta and gamma ) whereas,
in rats, five forms have been found. The alpha subunit and beta subunit are of
approximately 47 kD and 45 kD, respectively. The gamma gamma and alphagamma enolases are located mainly in the nervous tissue and neuroendocrine
cells.

Neurofilaments constitute the main structural elements of neuronal axons anddendrites. Neurofilaments are composed of three major subunits referred to as theneurofilament triplet, with molecular weights of 68 kD, 160kD and 200 kD.
Within tumors, only neoplastic cells of neural origin or those exhibiting neuronaldifferentiation, have been reported to express neurofilaments.
Neurofilament 200kD is recommended for the detection of specific antigens
of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

Neuron Specific Enolase is recommended for the detection of specific antigens
of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.
PRODUCT SPECIFIC INFORMATION
Clone 22C9 reacts with the gamma subunit of the enolase isoenzyme.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Nitric Oxide Synthase 1

Oct-02

Human small intestine: immunohistochemical staining for nitric oxide synthase 1. Notecytoplasmic staining of enteric ganglia. Nitric Oxide Synthase 1: clone NOS-125

Human tonsil: immunohistochemical staining for Oct-2. Note strong staining of germinal
centre B-cells. Oct-2: clone Oct-207

NOS-125

Oct-207

FORMAT

CODE

USAGE

US

EU

ROW*

FORMAT

CODE

USAGE

US

EU

ROW*

Liquid 1 mL

NCL-L-NOS-1

P(HIER)

IVD--

BOND 7 mL

PA0532P(HIER)

IVD

IVD

IVD

PATHOLOGY MENUPATHOLOGY MENUNEUROPATHOLOGYHEMATOPATHOLOGYSANTIGEN BACKGROUNDANTIGEN BACKGROUND

Human nitric oxide synthases are a family of enzymes responsible for thesynthesis of nitric oxide (NO) from L-arginine and molecular oxygen. There are atleast three nitric oxide synthases; NOS-1, also known as neuronal NOS or nNOS,
NOS-2, which is referred to as inducible NOS or iNOS and NOS-3, also known asendothelial NOS or eNOS. As suggested by their nomenclature, these enzymes
have different cellular distribution and are subjected to different regulatory
mechanisms. NOS-3 is reported to be constitutively expressed and produces
picomolar quantities of NO which play a role in signal transmission resulting
in physiological effects. In the gastrointestinal tract, NO is reported to play aprotective role where it has direct microbiocidal properties and acts as a first lineof mucosal defence in the stomach. The function of NO in tumor development,
promotion and progression is unclear. The effects may be both beneficial but also
detrimental to those individuals with gastric cancer, where it is reported that NO
supports tumor progression through the creation of neovasculature.

Oct-2 is a transcription factor belonging to the POU homeo-domain family thatbinds to the Ig gene octamer sites regulating B cell specific genes. It is dependent
on the activity of B cell restricted coactivators such as BOB.1/OBF.1. Oct-2 protein
expression is not restricted to B cells, although expression levels are muchhigher in these cells. Reports indicate that germinal center B cells shows higher
expression for Oct-2 and BOB.1/OBF.1. In addition, Oct-2 expression is reported
to be significantly greater in germinal center derived lymphomas, although otherB cell lymphomas also display high levels of expression. Reed Sternberg (RS)cells represent the malignant cells in classical Hodgkin’s disease and are derived
from germinal center B cells. In a number of these cases, cells do not express
immunoglobulin due to the presence of crippling mutations within the Ig genes.
As Ig gene expression in B cells also requires an interaction between octamersites and the transactivating factors Oct-2 and BOB.1, the absence of both Oct-2
and BOB.1 expression represents a novel mechanism for immunoglobulin genederegulation in RS cells.

Nitric Oxide Synthase 1 is recommended for the detection of specific antigens
of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

Oct-2 is recommended for the detection of specific antigens of interest in normal
and neoplastic tissues, as an adjunct to conventional histopathology using nonimmunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Oct-3/4

p16

Human testes, seminoma: immunohistochemical staining for Oct-3/4. Oct-3/4: clone N1NK

Squamous Cell Carcinoma of tonsil: immunohistochemical staining for p16. p16: clone 6H12

N1NK

6H12

FORMAT

CODE

USAGE

US

EU

ROW*

FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0193P(HIER)

IVD

IVD

IVD

BOND 7 mL

PA0016P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-OCT3/4

P(HIER)

IVD

IVD

IVD

S

PATHOLOGY MENU
HEAD, NECK AND ENDOCRINE

N1NK (Previous Formulation)
FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0934P(HIER)

IVD

IVD

IVD

ANTIGEN BACKGROUND
p16 (INK4a) (Cyclin-dependent kinase inhibitor 2A (CDKN2A)) is a tumour
suppressor protein associated with cell cycle progression, specifically in theregulation of transition from G1 phase of the cell cycle in to the S phase.
Oncogenic mutations in the CDKN2A gene that encodes p16 (resulting in over orunder expression of the protein) is associated with a wide range of cancers andcancer precursor lesions. Immunohistochemical identification of p16 is particularly
relevant in oro-pharyngeal squamous cell carcinoma (OPSCC) and uterine cervicallesions, where expression is seen in the cytoplasm and nucleus of neoplastic cells.

PATHOLOGY MENUGYNEPATHOLOGYANTIGEN BACKGROUND
Oct-3/4 is a member of the POU homeodomain family of transcription factors,
which is expressed by embryonic stem cells and germ cells. A critical amountof Oct-3/4 is required to maintain stem cell self replication. Down regulation of
Oct-3/4 levels are associated with loss of pluripotency. Oct-3/4 has been proposed
as a useful marker for germ cell tumors which exhibit features of pluripotentiality,
including seminoma/dysgerminoma/germinoma and embryonal carcinoma, andestablishing a germ cell origin for some metastatic tumors of uncertain primary
origin.

p16 is recommended for the detection of specific antigens of interest in normal
and neoplastic tissues, as an adjunct to conventional histopathology using nonimmunologic histochemical stains.

Oct-3/4 is recommended for the detection of specific antigens of interest in normal
and neoplastic tissues, as an adjunct to conventional histopathology using nonimmunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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p21 (WAF1 Protein)

p53 Protein

Squamous cell carcinoma: immunohistochemical staining of p21(WAF1): clone 4D10

Human ductal carcinoma of the breast: immunohistochemical staining of p53 Protein.
p53: clone DO-7

4D10
FORMAT

CODE

USAGE

US

EU

ROW*

Liquid 1 mL

NCL-L-WAF-1

P(HIER)

RUO

RUO

RUO

S

DO-7

PATHOLOGY MENUSPECIALIZEDFORMAT

CODE

USAGE

US

EU

BOND 7 mL

ROW*

PA0057P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-p53-DO7

P

IVD

IVD

IVD/RUOPATHOLOGY MENU
BREAST PATHOLOGYANTIGEN BACKGROUND
The gene encoding WAF1, also termed p21, is transcriptionally regulated by the
suppressor protein, p53. Overexpression of WAF1 is growth suppressive, possibly
by inhibiting the activity of cyclin/CDK complexes. One consequence of WAF1
binding to cyclin/CDK complexes is the inhibition of Rb protein phosphorylation.
Induction of WAF1 expression requires wild type p53 activity in cells undergoing
p53 dependent G1 arrest or apoptosis. Mutation of the p53 gene is a common
event in human cancer and results in the failure to produce WAF1. The effect of
this may lead to uncontrolled cell proliferation.

ANTIGEN BACKGROUNDThis monoclonal antibody recognizes both wild type and mutant forms ofhuman p53 protein under denaturing and non-denaturing conditions. The epitope
recognized by clone DO-7 can be destroyed by prolonged fixation in bufferedformalin. The heat induced epitope retrieval technique may improve staining insome cases.
p53 Protein is recommended for the detection of specific antigens of interest in
normal and neoplastic tissues, as an adjunct to conventional histopathology using
non-immunologic histochemical stains.
PRODUCT SPECIFIC INFORMATIONThis monoclonal antibody recognizes both wild type and mutant forms ofhuman p53 protein under denaturing and non-denaturing conditions. The epitope
recognized by clone DO-7 can be destroyed by prolonged fixation in bufferedformalin.
The use of the heat induced epitope retrieval (HIER) technique can enhance
staining in some cases.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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p53 Protein (CM5)

p57 Protein (Kip2)

Western blot: detection of p53 protein (53 kD). Lane A, molecular weight markers. Lane B,
T3T3 mouse cell line immunoblotted, p53 Protein (CM5): Polyclonal

Human placenta: immunohistochemical staining for p57 protein. Note nuclear staining forcytotrophoblast and stromal cells of the villi. p57: clone 25B2

Polyclonal

25B2

FORMAT

CODE

USAGE

US

EU

ROW*

FORMAT

CODE

USAGE

US

EU

ROW*

Liquid 0.5 mL

NCL-L-p53-CM5p

P(HIER)

RUO

RUO

RUO

Liquid 1 mL

NCL-L-p57

P(HIER)

IVD

IVD

IVD

PATHOLOGY MENUPATHOLOGY MENUSPECIALIZEDSPECIALIZEDS

ANTIGEN BACKGROUNDANTIGEN BACKGROUND

The accumulation of p53 protein in response to genotoxic stress in vitro iswell established and appears to induce growth arrest and apoptosis by thetranscriptional regulation of other genes and possibly by other direct mechanisms.

Cyclin-dependent kinases are positive regulators of cell proliferation. p57 protein
acts as a tumor suppressor to counter this. It is closely related to other CDKIs
such as p21 protein (CIP1) and p27 protein (Kip1) as they share a common
structural N-terminal domain for binding to CDK/cyclin complexes and inhibiting
their kinase activity. Human p57 protein is found on chromosome 11p15.5, aregion which is reported to be a common site for loss of heterozygosity in certain
sarcomas, Wilms’ tumors and tumors associated with the Beckwith-Wiedemannsyndrome. There is increasing interest in p57 as a marker in gestational disease.
Gestational trophoblastic disease refers to a spectrum of proliferative disorders of
the placental trophoblast, with a wide range of histologic appearances and clinicalbehaviors. Recent developments in changes in the criteria for histologic diagnosisof these lesions due to earlier clinical diagnosis have been reviewed Hui P et al.,Advantages in Anatomical Pathology. 12(3): 116-125 (2005) and the ability to makemore accurate diagnoses due to the introduction of newer antibodies such as p57
is discussed.

PRODUCT SPECIFIC INFORMATION
NCL-L-p53-CM5p is specific for mouse and rat p53 protein.

p57 Protein (Kip2) is recommended for the detection of specific antigens
of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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p63 Protein

p120 Catenin

Human prostate: immunohistochemical staining for p63. Note nuclear staining of basal cellsof prostatic glands. p63: clone 7JUL

Human breast carcinoma: immunohistochemical staining for p120 Catenin antigen.
p120 Catenin: clone EP66

7JUL

EP66

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FORMAT

CODE

USAGE

US

EU

ROW*

FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0103P(HIER)

-

IVD

IVD

BOND 7 mL

PA0379P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-p63

P(HIER)

-

IVD

IVD

S

PATHOLOGY MENUPATHOLOGY MENU

BREAST PATHOLOGYUROPATHOLOGYANTIGEN BACKGROUNDANTIGEN BACKGROUND

p120 Catenin is a regulator of cell-cell adhesion, achieved through interaction withclassical and Type II cadherins. Evidence also exists for a role in the regulationof cadherin availability on the cell surface. p120 Catenin also regulates actin
dynamics, placing it as a potential master regulator of the cell motility/celladhesion phenotypes.

p63 is a type II integral membrane protein predominantly localized in the roughendoplasmic reticulum.
p63 is reported to be expressed in a number of normal tissues including
proliferating cells of the epithelium, cervix, urothelium and prostate.

Recent studies have suggested a tumor-suppression role for p120, with loss of
p120 expression implicated in the development of a tumor microenvironment andinduction of metastatic progression. The expression of p120 Catenin has beenhighlighted in early lobular breast neoplasias.

p63 is also reported to be expressed in most poorly differentiated squamous cell
carcinomas.
p63 Protein is recommended for the detection of specific antigens of interest in
normal and neoplastic tissues, as an adjunct to conventional histopathology using
non-immunologic histochemical stains.

p120 Catenin is recommended for the detection of specific antigens of interest in
normal and neoplastic tissues, as an adjunct to conventional histopathology using
non-immunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Parathyroid Hormone (PTH)

Pax-5

Human parathyroid adenoma: immunohistochemical staining for Parathyroid Hormone.
Parathyroid Hormone: clone 105G7

Human tonsil: immunohistochemical staining for Pax-5. Note nuclear staining of B cells.
Pax-5: clone 1EW

105G7

1EW

S

FORMAT

CODE

USAGE

US

EU

ROW*

FORMAT

CODE

USAGE

US

EU

Liquid 1 mL

NCL-L-PTH-488

P(HIER)

IVD

IVD

IVD

BOND 7 mL

PA0552P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-PAX-5

P(HIER)

IVD

IVD

IVD/RUOPATHOLOGY MENU
HEAD, NECK AND ENDOCRINEROW*

PATHOLOGY MENUHEMATOPATHOLOGYANTIGEN BACKGROUNDANTIGEN BACKGROUND

The parathyroid glands are small, oval, endocrine glands closely associated withthe thyroid gland. The parathyroid glands regulate serum calcium and phosphatelevels via parathyroid hormone (parathormone). Parathyroid hormone raises serum
calcium levels directly, by increasing the rate of osteoclastic reabsorption andpromoting breakdown of the bone matrix, and indirectly, by increasing the renal
tubular reabsorption of calcium ions and inhibiting the reabsorption of phosphateions from the glomerular filtrate, and finally, by promoting the absorption of
calcium from the small intestine. Parathyroid hormone is the most important
regulator of blood calcium levels and is essential to life, whereas calcitonin
appears only to provide a complementary mechanism for fine adjustment. Chiefcells are the most abundant cells in the parathyroid gland and are responsible forthe secretion of parathyroid hormone.

Pax genes are a family of developmental control genes that encode nuclear
transcription factors and have been implicated in the control of mammaliandevelopment. Pax-5 is a B cell specific transcription factor that is expressed in
pro B cells, pre-B and mature B cells, and subsequently in all stages of B cell
development until the plasma cell stage in which it is downregulated.
Pax-5 is recommended for the detection of specific antigens of interest in normal
and neoplastic tissues, as an adjunct to conventional histopathology using nonimmunologic histochemical stains.

Parathyroid Hormone (PTH) is recommended for the detection of specific antigens
of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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PD-L1

Perforin

Non-small cell lung cancer: immunohistochemical staining for PD-L1. PD-L1: clone 73-10

Human follicular lymphoma: immunohistochemical staining for Perforin. Perforin: clone 5B10

73-10

5B10

FORMAT

CODE

USAGE

US

EU

ROW*

FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0832P (HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-PERFORINP(HIER)IVD--

PATHOLOGY MENUPATHOLOGY MENULUNG PATHOLOGYHEMATOPATHOLOGYANTIGEN BACKGROUNDANTIGEN BACKGROUND

Programmed death-ligand 1 (PD-L1), CD274 or B7 Homolog 1(B7-H1) is a protein
encoded by the CD274 gene. When bound to its ligands, PD-1 and B7.1, it plays
an immunosuppressive role by inhibiting T-cell activity. Overexpression of PD-L1
by cancer cells may enable them to evade the host immune response, conferringa growth advantage to such tumours. PD-L1 expression levels detected byimmunohistochemistry can therefore be of prognostic value in some types ofcancer.

Perforin is a pore-forming protein found in cytoplasmic granules of cytotoxic
T-lymphocytes (CTLs). CTLs bind to cells which express foreign antigens andinduce them to lyze. Perforin forms circular lesions on the target cell membrane
similar to those induced by complement. Perforin and C9 share a high degree ofhomology particularly at the membrane spanning region. Perforin is reported tobe constitutively expressed in human CD3 negative, CD56 positive NK cells, CD3
positive large granular lymphocytes and gamma/delta T cells. This expression issignificantly induced in CD8 positive T cells but to a lesser extent in gamma/delta
T cells and NK cells. The induction of perforin mRNA is partially blocked by the
immunosuppressive drug cyclosporin A.

PD-L1 is recommended for the detection of specific antigens of interest in normal
and neoplastic tissues, as an adjunct to conventional histopathology using nonimmunologic histochemical stains.

Perforin is recommended for the detection of specific antigens of interest in
normal and neoplastic tissues, as an adjunct to conventional histopathology using
non-immunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Placental Alkaline Phosphatase

Polo-Like Kinase 1 (PLK-1)

Human seminoma: immunohistochemical staining of Placental Alkaline Phosphatase.
Placental Alkaline Phosphatase (PLAP): clone 8A9

Squamous cell carcinoma of oropharangeal tissue: immunohistochemical staining of PLK-1.
Polo-Like Kinase-1: clone MJS1

8A9

MJS1

FORMAT

CODE

USAGE

US

EU

ROW*

FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0161

P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-PLK-1

P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-PLAP-8A9

P(HIER)

IVD

IVD

IVD

S

PATHOLOGY MENUPATHOLOGY MENUSPECIALIZEDGYNEPATHOLOGYANTIGEN BACKGROUNDANTIGEN BACKGROUND

Polo-Like Kinase-1 (PLK1) (also known as Serine/Threonine Protein Kinase 13) isa 66 kDa kinase. The activity of PLK-1 is crucial for mitosis and maintenance ofgenome stability. PLK-1 localizes to centrosomes and kinetochores where it plays a
key role in late prophase and prometaphase. PLK-1 is overexpressed in many typesof cancers and mediates estrogen receptor-mediated gene transcription in breast
cancer cells.

Placental alkaline phosphatase (PLAP) is a membrane-associatedsialoglycoprotein enzyme normally present at high concentration insyncytiotrophoblasts within the placenta during the third trimester of gestation.
The expression of PLAP was originally thought to be restricted to term placenta
but a human PLAP-like variant has been described which shares more than
85% homology with PLAP itself. This high degree of homology between PLAP
and PLAP-like enzyme together with cross-reacting antibodies has led to some
confusion of the distribution of PLAP and PLAP-like enzyme in various tissues.
PLAP is reported to be expressed only in normal term placenta, endocervix andfallopian tube and also in ovarian and proximal gastrointestinal tumors. PLAP
expression is rare in malignant germ cell tumors. PLAP-like enzyme is reported
to be predominantly found in normal fetal and neonatal testis, and in thymus. It
is also commonly expressed in germ cell tumors and more recently described inseminomas.

Overexpression of PLK-1 is associated with tumor development, with elevatedlevels of expression reported in non-small cell lung cancers, head and neck,gastric, breast, ovarian, colon and several other cancer types.
Polo-Like Kinase 1 (PLK-1) is recommended for the detection of specific antigens
of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

Placental Alkaline Phosphatase is recommended for the detection of specificantigens of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Progesterone Receptor (A/B Forms)
A

Breast carcinoma: immunohistochemical staining of Progesterone Receptor. Note the nuclear
staining in a proportion of tumor cells. Progesterone Receptor: clone 16

Human fibroadenoma (serial sections): immunohistochemical staining for Progesterone
Receptor (A and B forms). Note a smaller proportion of weakly staining tumor cell nuclei in
A compared to B. Progesterone Receptor (A/B Forms): clones 16/SAN27

16
FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0312P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-PGR-312

P(HIER)

IVD

IVD

IVD

Liquid 2 mL

NCL-L-PGR-312/2

P(HIER)

-

IVD

IVD

B

16/SAN27
FORMAT

CODE

USAGE

US

EU

ROW*

Liquid 1 mL

NCL-L-PGR-AB

P(HIER)

-

IVD

IVD

PATHOLOGY MENU
BREAST PATHOLOGY

1A6
FORMAT

CODE

USAGE

US

EU

ROW*

Liquid 1 mL

NCL-L-PGR

P(HIER)

-

IVD

IVD

ANTIGEN BACKGROUND
The human progesterone receptor (PR) is expressed as two isoforms, PRA (94 kD)
and PRB (114 kD), which function as ligand-activated transcription factors. In vitro
studies have indicated that PRA and PRB can activate different target genes andthat PRA, in some circumstances, may act as a dominant inhibitor of the functionof PRB and other steroid hormone receptors. PRA and PRB are both expressed innormal breast. Most endometrial carcinomas, however, are reported to express
only one isoform with either PRA or PRB being expressed.

PATHOLOGY MENU
BREAST PATHOLOGYANTIGEN BACKGROUND
The human progesterone receptor (PR) is expressed as two isoforms, PRA (94kD) and PRB (114 kD), which function as ligand-activated transcription factors.
These two isoforms are transcribed from distinct estrogen receptor (ER)-inducible
promoters within a single copy PR gene.

Progesterone Receptor (A/B Forms) is recommended for the detection of specificantigens of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.
PRODUCT SPECIFIC INFORMATIONThe PRA form is a truncated version of the PRB form, lacking the first 164
N-terminal amino acids. In humans, PRA acts as a transdominant repressor of thetranscriptional activity of PRB, glucocorticoid receptor, ER, androgen receptor andmineralocorticoid receptor. PRB functions mainly as a transcriptional activator.
PRB is expressed strongly in endometrial glandular and stromal nuclei in the
proliferative phase of the menstrual cycle and weakly during the secretory phaseand early pregnancy.

The cocktail has been formulated using two clones, clone 16, specific for PRA, andSAN27, specific for PRB.

Progesterone Receptor is recommended for the detection of specific antigens
of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.
PRODUCT SPECIFIC INFORMATION
Clone 16 is specific for a region of the N-terminus of the A form of PR. The precise
epitope has not been mapped but it reacts with both A and B forms of PR byWestern Blot but only with the A form by immunohistochemistry. This suggeststhat the epitope is inaccessible in the native folded B form of the protein.
Refer to the IFU for appropriate use instructions.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Prostate Specific Antigen

Prostate Specific Membrane Antigen

Human prostatic hyperplasia: immunohistochemical staining of Prostate Specific Antigen.
Prostate Specific Antigen: clone 35H9

Human prostate: immunohistochemical staining for Prostate Specific Membrane Antigen(PSMA): clone 1D6

35H9

1D6

FORMAT

CODE

USAGE

US

EU

ROW*

FORMAT

CODE

BOND 7 mL

PA0431

P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-PSMA

Liquid 1 mL

NCL-L-PSA-431

P

IVD

IVD

IVD

USAGE
-

US

EU

ROW*

ASR

RUO

RUO

PATHOLOGY MENUPATHOLOGY MENU

UROPATHOLOGYUROPATHOLOGYANALYTE SPECIFIC REAGENTANTIGEN BACKGROUND

Analyte Specific Reagent. Analytical and performance characteristics are notestablished.

Prostate specific antigen (PSA) is a 34 kD protein belonging to the kallikrein familyof serine proteases and was originally isolated and purified from human seminal
plasma. It was found to be immunologically identical and biologically similar toa protein isolated from the prostate gland. PSA is distinct from prostatic acidphosphatase. Low levels of expression of PSA have been reported in non-prostatic
tissues and tumors such as breast carcinomas.
Prostate Specific Antigen is recommended for the detection of specific antigens
of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Prostatic Acid Phosphatase

Protein Gene Product 9.5

Human prostate, adenocarcinoma: immunohistochemical staining for prostatic acidphosphatase. Prostatic Acid Phosphatase: clone PASE/4LJ

Human colon: immunohistochemical staining of Protein Gene Product 9.5. Note the staining
in the neuronal elements and the ganglia of the longitudinal and circular smooth muscle.
Protein Gene Product 9.5: clone 10A1

PASE/4LJ
FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0006

P

IVD

IVD

IVD

NCL-L-PAP

F;P

RUO

RUO

RUO

Liquid 1 mL

S

10A1

PATHOLOGY MENUFORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0286P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-PGP9.5

P(HIER)

IVD

IVD

IVD

PATHOLOGY MENU

UROPATHOLOGYNEUROPATHOLOGYANTIGEN BACKGROUNDANTIGEN BACKGROUND

Prostatic acid phosphatase (PAP) is an isoenzyme of acid phosphatase found inlarge amounts in the prostate and seminal fluid. The precise function of PAP is
unknown, but it may act as a hydrolase to split phosphoryl choline in semen andalso function as a transferase. Elevated serum levels of the enzyme are reported inmetastatic prostatic carcinoma.

Protein gene product (PGP) 9.5 is a neuron-specific protein, structurally andimmunologically distinct from neuron specific enolase. The protein which has amolecular weight of 27 kD was first identified by high resolution two dimensional
PAGE. PGP9.5 expression has been reported in neurons and nerve fibers at alllevels of the central and peripheral nervous system, in many neuroendocrine cells,in segments of the renal tubules, in spermatogonia and Leydig cells of the testis,in ova and in some cells of both the pregnant and non-pregnant corpus luteum.
PGP9.5 is a member of the ubiquitin C-terminal hydroxylase family and is also
concentrated within inclusion bodies suggesting that such structures may be
metabolically active regions of the cells.

Prostatic Acid Phosphatase is recommended for the detection of specific antigens
of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

Protein Gene Product 9.5 is recommended for the detection of specific antigens
of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Retinoblastoma Gene Protein

S-100

Human tonsil: immunohistochemical staining for Retinoblastoma Gene Protein.
Retinoblastoma Gene Protein: clone 13A10

Human bowel: immunohistochemical staining for S-100. Note cytoplasmic staining of ganglia
and peripheral nerve cells. S-100: Polyclonal

13A10

EP32

FORMAT

CODE

USAGE

US

EU

ROW*

FORMAT

CODE

Liquid 1 mL

NCL-L-RB-358

P(HIER);W

RUO

RUO

RUO

BOND 7 mL
Liquid 0.1 mL

PATHOLOGY MENUSPECIALIZED

USAGE

US

EU

ROW*

PA0031

P(HIER)

IVD

IVD

IVD

NCL-L-S100-167

P(HIER)

IVD

IVD

IVD

PATHOLOGY MENU
DERMATOPATHOLOGYANTIGEN BACKGROUNDANTIGEN BACKGROUND

Retinoblastoma (Rb) is a rare tumor of the retina associated with mutations ofchromosome 13. The nuclear phosphoprotein encoded by the Rb tumor suppressor
gene is present in many cells and may indirectly regulate cell growth by activating
the transcription factor ATF-2. Activation of ATF-2 initiates expression of TGFbeta2, which in turn inhibits transcription of genes affecting cell growth. Bilateralmutation of the Rb gene may potentially play a role in the development of a numberof malignant tumors.

S-100A and S-100B proteins are two members of the S-100 family of proteins.
S-100A is composed of an alpha and beta chain, whereas S-100B is composedof two beta chains. S-100 protein is reported to be expressed in neuroectodermal
tissue, including nerves and melanocytes. Langerhans cells in skin andinterdigitating reticulum cells in the paracortex of lymph nodes are also reported toexpress S-100 protein. It is noteworthy that S-100 protein is highly soluble and may
be eluted from frozen tissue during immunohistochemical procedures.

PRODUCT SPECIFIC INFORMATION

S-100 is recommended for the detection of specific antigens of interest in normal
and neoplastic tissues, as an adjunct to conventional histopathology using nonimmunologic histochemical stains.

NCL-L-RB-358 was raised to the N-terminal region of the Rb gene protein.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
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Sarcoglycan Antibodies

Serotonin

Transverse section of skeletal muscle fibers. immunohistochemical staining for Alpha
Sarcoglycan. Note the demonstration of localized Alpha Sarcoglycan to the sarcolemmaof the muscle fibers. Alpha Sarcoglycan: clone Ad1/20A6

Human bowel: immunohistochemical staining for Serotonin-containing mucosal cells.
Serotonin: Polyclonal

Polyclonal

Alpha Sarcoglycan: clone Ad1/20A6
FORMAT

CODE

USAGE

US

EU

ROW*

Liquid 1 mL

NCL-L-a-SARC

F

IVD

IVD

IVD

S

FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0736P(HIER)

IVD

IVD

IVD

PATHOLOGY MENU

Beta Sarcoglycan: clone βSarc1/5B1GASTROINTESTINAL PATHOLOGYFORMAT

CODE

USAGE

US

EU

ROW*

Liquid 1 mL

NCL-L-b-SARC

F

IVD

IVD

IVD

ANTIGEN BACKGROUND
Serotonin (5-hydroxytryptamine, 5-HT) is reported to be a widely distributed
neurotransmitter and hormone in the mammalian peripheral and central nervous
system (CNS). Serotonin is formed by the decarboxylation of 5-hydroxy-tryptophan,
its intermediate, which in turn is formed by hydroxylation of L-tryptophan bytryptophan hydroxylase. In the CNS, the action of serotonin is terminated byreuptake into the presynaptic terminal by specific serotonin transporters. Serotoninhas been implicated in several neuropsychiatric disorders such as anxiety,depression and schizophrenia. The majority of serotonergic nerve terminals in the
CNS originate in neuronal cell bodies of the Raphe nuclei (dorsal, median), nucleus
Raphe obscurus and nucleus Raphe pallidus in the brainstem which project tospecific areas of the brain and spinal cord. Serotonin is thought to be an inhibitory
neurotransmitter regulating a wide range of sensory, motor and cortical functionsin the CNS. In the periphery, serotonin is reported to be present in neural andnon-neural structures such as platelets, gastro-intestinal tract (myenteric plexus,
enterochromaffin cells), lungs (neuroepithelial cells), thyroid gland and spleen.

Delta Sarcoglycan: clone δSarc3/12C1
FORMAT

CODE

USAGE

US

EU

ROW*

Lyophilized 1 mL

NCL-d-SARC

F

IVD

IVD

IVD

Gamma: clone 35DAG/21B5
FORMAT

CODE

USAGE

US

EU

ROW*

Lyophilized 1 mL

NCL-g-SARC

F

IVD

IVD

IVD

PATHOLOGY MENUMUSCLE PATHOLOGY

Serotonin is recommended for the detection of specific antigens of interest in
normal and neoplastic tissues, as an adjunct to conventional histopathology using
non-immunologic histochemical stains.

ANTIGEN BACKGROUND
In normal skeletal muscle, dystrophin, the protein product of the gene which is
defective in Duchenne and Becker muscular dystrophy, is attached to the muscle
membrane via a complex of proteins (dystrophin-associated glycoproteins, DAGs).
Dystrophin-deficient muscle shows a generalized reduction in DAG labeling. The
expression of different members of the dystrophin glycoprotein complex is alteredin several types of muscular dystrophy. For example, patients with LGMD2D havemutations in the gene for alpha-sarcoglycan, those with LGM2E have mutationsin the beta-sarcoglycan gene, those with LGM2C have mutations in the gammasarcoglycan gene and those with LGM2F have mutations in the delta-sarcoglycan
gene. As the sarcoglycans function together as a sub-complex, mutations in any
one of the sarcoglycan genes usually results in variable expression for the wholegroup.
Sarcoglycan Antibodies are recommended for the detection of specific antigens
of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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SMA (Alpha Smooth Muscle Actin)

Spectrin

Human small bowel: immunohistochemical staining for Alpha Smooth Muscle Actin. Notecytoplasmic staining of the muscularis mucosa, vascular walls and smooth muscle fibers in
the lamina propria. SMA: clone αsm-1

Human striated muscle: immunohistochemical staining for Spectrin. Note membrane stainingof muscle fibers. Spectrin: clone RBC2/3D5

RBC2/3D5

αsm-1
FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0943

P

IVD

IVD

IVD

Liquid 1 mL

NCL-L-SMA

P

IVD

IVD

IVD

FORMAT

CODE

USAGE

US

EU

ROW*

Lyophilized 1 mL

NCL-SPEC1

F

IVD

IVD

IVD

PATHOLOGY MENUMUSCLE PATHOLOGYPATHOLOGY MENUMUSCLE PATHOLOGYANTIGEN BACKGROUND
Spectrin is a cytoskeletal protein which has some structural homology withdystrophin, the protein that is defective in Duchenne and Becker muscular
dystrophy. Subtle membrane damage frequently occurs during the excisionand freezing of muscle biopsies. Labeling for spectrin must be used to monitor
membrane integrity. NCL-SPEC1 recognizes the beta chain of spectrin inerythrocytes and muscle. NCL-SPEC1 reacts with human beta-spectrin.

ANTIGEN BACKGROUND
Cytoplasmic actins are part of the microfilament system of cytoskeletal proteins.
Smooth muscle actin is found in vascular walls, intestinal muscularis mucosae andmuscularis propria and in the stroma of various tissues.
SMA (Alpha Smooth Muscle Actin) is recommended for the detection of specificantigens of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

Spectrin is recommended for the detection of specific antigens of interest in
normal and neoplastic tissues, as an adjunct to conventional histopathology using
non-immunologic histochemical stains.

PRODUCT SPECIFIC INFORMATION
An enzyme pretreatment can be used to enhance staining in some cases.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Surfactant Protein A

Synaptophysin

Human lung adenocarcinoma: immunohistochemical staining for Surfactant Protein A.
Surfactant Protein A: clone 32E12

Breast carcinoma showing neuroendocrine differentiation: immunohistochemical staining for
Synaptophysin. Synaptophysin: clone 27G12

32E12

27G12

FORMAT

CODE

USAGE

US

EU

ROW*

FORMAT

CODE

Liquid 1 mL

NCL-L-SP-A

P(HIER)

IVD--

BOND 7 mL
Liquid 1 mL

PATHOLOGY MENULUNG PATHOLOGY

USAGE

US

EU

ROW*

PA0299P(HIER)

IVD

IVD

IVD

NCL-L-SYNAP-299

P(HIER)

IVD

IVD

IVD

S

PATHOLOGY MENU
HEAD, NECK AND ENDOCRINEANTIGEN BACKGROUNDANTIGEN BACKGROUND

Pulmonary surfactant plays a critical role in maintaining the structural integrityof the respiratory epithelium by reducing surface tension during expiration. It
is a lipoprotein complex which is synthesized and secreted into the alveoli ofthe lung by type II pneumocytes. Lung surfactant protein-A (SP-A) is a major
phospholipid-associated glycoprotein in surfactant and is a member of the C-type
lectin superfamily that also inhibits lipid secretion and enhances the uptake ofphospholipid by alveolar type II cells. Levels of SP-A in amniotic fluid are reported
to reflect the degree of fetal lung maturity and inadequate levels of surfactant atbirth, a frequent occurrence in premature infants, results in respiratory failure.

Synaptophysin is an integral membrane glycoprotein with a molecular weight of
38 kD. It is reported to occur in presynaptic vesicles of neurons in brain, spinal
cord, retina, in similar vesicles of the adrenal medulla as well as in neuromuscularjunctions.
Synaptophysin may be involved in synaptic vesicle formation and exocytosis.
Synaptophysin is reported to be expressed in a wide spectrum of neuroendocrine
tumors including neuroblastomas, ganglioneuroblastomas, phaeochromocytomas,
chromaffin and non-chromaffin paragangliomas.

Surfactant Protein A is recommended for the detection of specific antigens
of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

Synaptophysin is also reported to be expressed in neuroendocrine tumorsof epithelial type including pituitary adenomas, islet cell tumors, medullarycarcinomas of thyroid, parathyroid adenomas, carcinoids of the bronchopulmonary
and gastrointestinal tracts, neuroendocrine carcinomas of the bronchopulmonary
and gastrointestinal tract and neuronendocrine carcinomas of the skin.
Synaptophysin is recommended for the detection of specific antigens of interest in
normal and neoplastic tissues, as an adjunct to conventional histopathology using
non-immunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Tartrate-Resistant Acid Phosphatase(TRAP)

Terminal Deoxynucleotidyl Transferase

Human osteoclastoma: immunohistochemical staining for Tartrate-Resistant Acid
Phosphatase. Tartrate-Resistant Acid Phosphatase (TRAP): clone 26E5

Human thymus: immunohistochemical staining for Terminal Deoxynucleotidyl Transferase.
Note nuclear staining for cortical thymic lymphocytes. Terminal deoxynucleotidyl transferase:clone SEN28

26E5FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0093P(HIER)

IVD

IVD

IVD

NCL-L-TRAP

P(HIER)

IVD--

Liquid 1 mL

SEN28

PATHOLOGY MENUHEMATOPATHOLOGYFORMAT

CODE

USAGE

US

EU

BOND 7 mL

ROW*

PA0339P(HIER)

IVD

IVD

IVD

Liquid 0.5 mL

NCL-L-TDT-339

P(HIER)-

IVD

IVD/RUO

Liquid 1 mL

NCL-L-TDT-339

P(HIER)

IVD

IVD

IVD/RUOPATHOLOGY MENUHEMATOPATHOLOGYANTIGEN BACKGROUND
Tartrate-resistant acid phosphatase (TRAP) is a basic, iron-binding protein withhigh activity towards phosphoproteins, ATP and 4-nitrophenyl phosphate. This
isoenzyme has been reported through different applications to be expressed inhuman alveolar macrophages, osteoclasts, spleen and liver. Expression of TRAP isreported to be increased in the spleen and monocytes of individuals with Gaucher’sdisease, Hodgkin’s disease and the sera of individuals undergoing active boneturnover. Elevated levels are also reported to be associated with various B cell andT cell leukemias and lymphomas, decidual cells, syncytiotrophoblasts and somemacrophages distributed throughout maternal and embryonic tissues.

ANTIGEN BACKGROUND
Terminal deoxynucleotidyl transferase (TdT) is a DNA polymerase of 58 kD locatedin the cell nucleus which catalyzes the polymerization of deoxynucleotides at the
3’ hydroxyl ends of oligo or polydeoxynucleotide initiators and functions without atemplate. TdT is reported to be expressed in primitive T and B lymphocytes of thenormal thymus and bone marrow. The identification of TdT-positive cell populationsin primary and secondary lymphoid organs during maturation of the immune
system is one area of interest but it is the reported occurrence of high levels of
enzyme activity in white blood cells and bone marrow in certain leukemias which isof particular interest.

Tartrate-Resistant Acid Phosphatase (TRAP) is recommended for the detectionof specific antigens of interest in normal and neoplastic tissues, as an adjunct toconventional histopathology using non-immunologic histochemical stains.

Terminal Deoxynucleotidyl Transferase is recommended for the detection of
specific antigens of interest in normal and neoplastic tissues, as an adjunct toconventional histopathology using non-immunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Thyroglobulin

Thyroid Peroxidase

Human Thyriod: immunohistochemical staining of Thyroglobulin in the follicular epithelial
cells. Thyroglobulin: clone 1D4

Thyroid, Graves’ disease: immunohistochemical staining for Thyroid Peroxidase.
Thyroid Peroxidase: clone AC25

1D4

AC25

I

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FORMAT

CODE

USAGE

US

EU

ROW*

FORMAT

CODE

USAGE

US

EU

ROW*

Liquid 1 mL

NCL-L-THY

F;P

RUO

RUO

RUO

Liquid 1 mL

NCL-L-TPO

P(HIER)

IVD

IVD

IVD/RUOPATHOLOGY MENUPATHOLOGY MENU

HEAD, NECK AND ENDOCRINE

HEAD, NECK AND ENDOCRINEANTIGEN BACKGROUNDANTIGEN BACKGROUND

Thyroglobulin is a heavily glycosylated protein of 670kD composed of two
identical subunits and is synthesized by the follicular epithelial cells of the thyroid.
Thyroglobulin provides iodination sites for the formation of the thyroid hormones.

Thyroid peroxidase gene expression is under the regulation of thyroid stimulating
hormone. In normal thyroid, expression of thyroid peroxidase (TPO) described
immunohistochemically is reported to produce a diffuse, fine, granular cytoplasmic
stain in all follicular cells. Some studies have shown qualitative, as well as
quantitative differences in thyroid peroxidase expression in thyroid cancer
compared to normal tissue.
Thyroid Peroxidase is recommended for the detection of specific antigens
of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.
PRODUCT SPECIFIC INFORMATIONTPO stains optimally when used in TBS-based wash buffer and diluent systems.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Thyroid Stimulating Hormone

Thyroid Transcription Factor-1

Normal human pituitary gland: immunohistochemical staining for Thyroid Stimulating
Hormone. Note cytoplasmic staining of a proportion of anterior pituitary cells. Thyroid
Stimulating Hormone: clone QB2/6

Human small cell lung carcinoma: immunohistochemical staining with Thyroid Transcription
Factor-1. Thyroid Transcription Factor-1: clone SPT24

S

SPT24

QB2/6
FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0776P(ENZYME)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-TSH

P(ENZYME)

IVD

-

-

FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0364P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-TTF-1

P(HIER)

IVD

IVD

IVD

PATHOLOGY MENUPATHOLOGY MENULUNG PATHOLOGYHEAD, NECK AND ENDOCRINEANTIGEN BACKGROUNDANTIGEN BACKGROUND

Thyroid Transcription Factor-1 (TTF-1) is a member of the homeodomaintranscription factor family and plays a role in regulating genes expressed within
the thyroid, lung and brain. These include thyroglobulin, thyroid peroxidase, Claracell secretory protein and surfactant proteins. Human TTF-1 (38 kD) is a single
polypeptide of 371 amino acids sharing 98% homology with the equivalent rat
and mouse proteins. TTF-1 functions by binding to specific recognition sites in amanner that may be regulated by both the redox and phosphorylation status of theprotein. In addition to its role as a tissue-specific transcriptional activator in adultorgans, TTF-1 may also function in organogenesis. Gene targeting studies haveshown TTF-1 to be essential for the proper development of the thyroid and lungs
and abnormal expression may underline a number of congenital abnormalities.

Thyroid stimulating hormone (TSH) is a pituitary hormone of 28 kD which
stimulates thyroid growth and production of thyroid hormones. TSH is reported to
be expressed in thyrotrophic cells of the pituitary and pituitary adenomas.
Thyroid Stimulating Hormone is recommended for the detection of specificantigens of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

Thyroid Transcription Factor-1 is recommended for the detection of specificantigens of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Topoisomerase I

Topoisomerase II Alpha

Human tonsil: immunohistochemical staining for Topoisomerase I. Topoisomerase I: clone 1D6

Human bladder tumor: immunohistochemical staining for Topoisomerase II alpha.
Topoisomerase II Alpha: clone 3F6

1D6
FORMAT

CODE

USAGE

US

EU

ROW*

Liquid 1 mL

NCL-L-TOPO I

P(HIER)

IVD

-

-

E

S

3F6

PATHOLOGY MENUFORMAT

CODE

USAGE

US

EU

ROW*

Liquid 1 mL

NCL-L-TOPOIIA

P(HIER)IVD--

PATHOLOGY MENUSPECIALIZEDSPECIALIZEDANTIGEN BACKGROUNDANTIGEN BACKGROUND

Topoisomerases are nuclear enzymes involved in a variety of cellular activities
such as chromosomal condensation, DNA replication, transcription, recombinationand segregation at mitosis. Human Topoisomerase I is a 100 kD protein capableof relaxing positively and negatively supercoiled DNA by performing a transient
single-stranded nick which is then re-ligated at the end of the reaction. It has beenshown that the enzyme is located in regions of the genome that are undergoing
active RNA synthesis where it probably reduces superhelical stresses in the DNA
enabling RNA polymerase to function properly. In normal eukaryotic cells, DNA
topoisomerase I does not show relevant fluctuations across the cell cycle, unlike
DNA topoisomerase II alpha. Both DNA topoisomerases I and II have been foundto be targets of autoantibodies in the sera of individuals with certain autoimmune
diseases, for example, systemic lupus erythematosus and also of some anti-tumor
drugs and antibiotics. Elevated levels of DNA topoisomerase I, detected by 32Ptransfer assays, have been reported in colorectal tumors compared with normalcolon mucosa as a result of increased transcription or mRNA stability.

Topoisomerase II alpha is an essential nuclear enzyme involved in DNA replicationand is a target for many anti-cancer drugs used for cancer therapy. Decreased
expression of topoisomerase II alpha is the predominant mechanism of resistanceto several chemotherapeutic agents. A significant variation in the range of
expression of this protein has been reported in many different tumors. Reportsof the analysis of primary breast tumors have indicated that topoisomerase II
beta is more widely expressed than topoisomerase II alpha. Topoisomerase IIalpha expression and activity is linked to the cell cycle and is associated with theproliferation status of cells.
Topoisomerase II Alpha is recommended for the detection of specific antigens
of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.

Topoisomerase I is recommended for the detection of specific antigens of interestin normal and neoplastic tissues, as an adjunct to conventional histopathology
using non-immunologic histochemical stains.
PRODUCT SPECIFIC INFORMATIONThe use of phosphate-containing wash buffers or diluents can have an adverse
effect on staining. Tris-containing wash buffers or diluents should be used instead.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Tyrosinase

Tyrosine Hydroxylase

Human malignant melanoma: immunohistochemical staining for Tyrosinase: clone T311

Human midbrain: immunohistochemical staining of Tyrosine Hydroxylase enzyme. Notecytoplasmic staining of catecholaminergic cells and their processes. (Peroxidase substrate:
nickel DAB, Counterstain: eosin). Tyrosine Hydroxylase: clone 1B5

T311
FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0322P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-TYROSP(HIER)

IVD

IVD

IVD/RUO

1B5
FORMAT

CODE

USAGE

US

EU

ROW*

Liquid 1 mL

NCL-L-TH

P(HIER)IVD--

PATHOLOGY MENUPATHOLOGY MENU

DERMATOPATHOLOGYNEUROPATHOLOGYANTIGEN BACKGROUNDANTIGEN BACKGROUND

The biosynthesis of melanin in melanocytes involves a family of enzymes, a key
member of which is tyrosinase. Tyrosinase deficiency is associated with various
forms of albinism and in particular oculocutaneous albinism. L-tyrosinase is
the initial substrate for melanin biosynthesis and its conversion to dopaquinone
is catalyzed by tyrosinase, whose expression is reported in melanocytes andmelanomas.

Tyrosine hydroxylase is the first enzyme in catecholamine (CA) biosynthesis andcatalyzes the conversion of L-tyrosine to L-DOPA. Tyrosine hydroxylase is reported
to be expressed in all CA neurons. Despite the abundant data about the distributionof catecholaminergic neurons in a wide variety of species, data on their distribution
in the human brain is less comprehensive. However, one such study has reported
that tyrosine hydroxylase products in the substantia nigra were restricted to neuralbodies, axons and dendrites. These in turn were restricted to the third decadeof life and their number increased in this location with age. This finding may berelated to ageing of melanin-pigmented neurons.

Tyrosinase is recommended for the detection of specific antigens of interest in
normal and neoplastic tissues, as an adjunct to conventional histopathology using
non-immunologic histochemical stains.

Tyrosine Hydroxylase is recommended for the detection of specific antigens
of interest in normal and neoplastic tissues, as an adjunct to conventional
histopathology using non-immunologic histochemical stains.
PRODUCT SPECIFIC INFORMATION
TH is reactive with tyrosine hydroxylase in human, mouse and rat brain tissue.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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Utrophin

N

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Vascular Endothelial Growth Factor
Receptor-3

A

B

Human skeletal muscle: immunohistochemical staining for Utrophin. In control muscle theantibody labels blood vessels and neuromuscular junctions (A). Utrophin is expressed at thesarcolemma in individuals with mutations in the DMD gene (B). Utrophin: clone DRP3/20C5

Human placenta: immunohistochemical staining for Vascular Endothelial Growth Factor
Receptor-3: clone KLT9KLT9DRP3/20C5
FORMAT

CODE

USAGE

US

EU

ROW*

Lyophilized 2.5 mL

NCL-DRP2

F

IVD

IVD

IVD

FORMAT

CODE

Liquid 1 mL

NCL-L-VEGFR-3

USAGE
-

US

EU

ROW*

ASR

RUO

RUO

PATHOLOGY MENUPATHOLOGY MENUSPECIALIZEDMUSCLE PATHOLOGYANALYTE SPECIFIC REAGENTANTIGEN BACKGROUND

Analyte Specific Reagent. Analytical and performance characteristics are notestablished.

The utrophin gene is located on chromosome 6. The protein is a homologue ofdystrophin and is known as dystrophin-related protein. In normal muscle, utrophin
is restricted to neuromuscular junctions; however, in dystrophin-deficient muscle,
utrophin expression may be upregulated and labeling appears around the peripheryof most fibers. lmmunohistochemical staining with DRP2 labels vessels andneuromuscular junctions and the upregulated form of utrophin, located aroundfiber membranes.
Utrophin is recommended for the detection of specific antigens of interest in
normal and neoplastic tissues, as an adjunct to conventional histopathology using
non-immunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

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VillinVimentin

Human large bowel: immmunohistochemical staining for Villin. Note cytoplasmic staining of
the epithelial cells. Villin: clone CWWB1Spindle cell carcinoma: immmunohistochemical staining for Vimentin. Vimentin: clone V9

V9

CWWB1
FORMAT

CODE

USAGE

Liquid 1 mL

NCL-L-VILLIN

-

US

EU

ROW*

ASR

RUO

RUO

S

PATHOLOGY MENUGASTROINTESTINAL PATHOLOGYFORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0640P(HIER)

IVD

IVD

IVD

Liquid 0.5 mL

NCL-L-VIM-V9

P(HIER)

IVD

IVD

IVD/RUO

Liquid 1 mL

NCL-L-VIM-V9

P(HIER)

IVD

IVD

IVD/RUO

SRL33

ANALYTE SPECIFIC REAGENT
Analyte Specific Reagent. Analytical and performance characteristics are notestablished.

FORMAT

CODE

USAGE

US

EU

ROW*

Liquid 1 mL

NCL-L-VIM-572

P(HIER)

IVD

IVD

IVD

PATHOLOGY MENU
TUMOR DIFFERENTIATIONANTIGEN BACKGROUND
Eukaryotic cells contain a number of types of cytoplasmic filamentous proteins,
microtubule, microfilaments and intermediate-sized filaments (IF). Vimentin, a 57
kD protein that is an intermediate filament is reported to be expressed in most cellsof mesenchymal origin, including fibroblasts, endothelial cells, smooth muscle,melanocytes as well as T and B lymphocytes.
Vimentin is recommended for the detection of specific antigens of interest in
normal and neoplastic tissues, as an adjunct to conventional histopathology using
non-immunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

149

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von Willebrand Factor(Factor VIII-related antigen)Wilms’ Tumor

Human tonsil: immunohistochemical staining for von Willebrand Factor. Note cytoplasmic
staining of endothelial cells. Von Willebrand Factor: clone 36B11

Human kidney: immunohistochemical staining for Wilms’ tumor. Wilms’ Tumor: clone WT49

WT49

36B11
FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0055P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-vWF

P(HIER)

IVD

IVD

IVD/RUOSFORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0562P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-WT1-562

P(HIER)

IVD

IVD

IVD

PATHOLOGY MENUPATHOLOGY MENU

UROPATHOLOGYSOFT TISSUE PATHOLOGYANTIGEN BACKGROUNDANTIGEN BACKGROUND
Human von Willebrand factor (or factor VIII-related antigen) is a 270 kD multimeric
plasma glycoprotein. It mediates platelet adhesion to injured vessel walls andserves as a carrier and stabilizer for coagulation factor VIII. The von Willebrandfactor has functional binding domains to platelet glycoprotein Ib, glycoprotein Ib/
IIIa, collagen and heparin. Von Willebrand factor is synthesized by endothelial cells
and is reported to be expressed in a number of tumors of vascular origin.

Wilms’ tumor protein (WT1) has a role in transcriptional regulation and isexpressed in the kidney and a subset of hematopoietic cells. Alteration oftranscription factor function is a common mechanism in oncogenesis. The WT1protein contains a DNA binding domain and any deletions or point mutations of theWT1 gene which destroy this activity result in the development of the childhood
nephroblastoma Wilms’ tumor and Denys-Drash syndrome. The description of WT1
involvement in nephroblastoma is not clear.

von Willebrand Factor (Factor VIII-related antigen) is recommended for thedetection of specific antigens of interest in normal and neoplastic tissues, as an
adjunct to conventional histopathology using non-immunologic histochemical
stains.

Wilms’ Tumor is recommended for the detection of specific antigens of interest in
normal and neoplastic tissues, as an adjunct to conventional histopathology using
non-immunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

150

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ZAP-70

Human B cell chronic lymphocytic leukemia: immunohistochemical staining for ZAP-70
antigen. ZAP-70: clone L453R

L453R
FORMAT

CODE

USAGE

US

EU

ROW*

BOND 7 mL

PA0998P(HIER)

IVD

IVD

IVD

Liquid 1 mL

NCL-L-ZAP-70

P(HIER)

IVD

IVD

IVD

PATHOLOGY MENUHEMATOPATHOLOGYANTIGEN BACKGROUND
ZAP-70 is a member of the syk family of proteins. It is expressed on T cells andNK cells and is required for the T cell receptor activation that triggers an immune
response. CLL B cells that express the non-mutated immunoglobulin VH genes
express levels of ZAP-70 protein that are comparable to those found in the blood T
cells of healthy adults. Leukemic cells that express mutated Ig VH genes generally
do not express detectable levels of ZAP-70 protein and this is correlated with thehigh level expression of CD38.
ZAP-70 is recommended for the detection of specific antigens of interest in normal
and neoplastic tissues, as an adjunct to conventional histopathology using nonimmunologic histochemical stains.

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

151

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C E L L M A R Q U E
BOND RTU FORMAT ANTIBODIES
NAME

CLONE

FORMAT

CODE

USAGE

US

EU

ROW*

PRETREATEMENT

7 mL Arginase-1 (SP156 Rab) 'CM'

SP156

7 mL BRTU

PA0791

HIER

IVD

-

-

ER1 207 mL C4d (SP91 Rab) 'CM'

SP91

7 mL BRTU

PA0792

HIER

IVD

-

-

ER1 207 mL CD163 (MRQ-26 Mab) 'CM'

MRQ-26

7 mL BRTU

PA0794

HIER

IVD

-

-

ER2 207 mL Cytokeratin 5/6 (D5 & 16B4 Mab) 'CM'

D5 & 16B4

7 mL BRTU

PA0795

HIER

IVD

-

-

ER2 207 mL Podoplanin (D2-40 Mab) 'CM'

D2-40

7 mL BRTU

PA0796

HIER

IVD

-

-

ER1 307 mL Ep-CAM (MOC31 Mab) 'CM'

MOC31

7 mL BRTU

PA0797

EIER

IVD

-

-

ENZ 1 107 mL GATA3 (L50-823 Mab) 'CM'

L50-823

7 mL BRTU

PA0798

HIER

IVD

-

-

ER1 5

7 mL Glypican-3 (1G12 Mab) 'CM'

1G12

7 mL BRTU

PA0800

HIER

IVD

-

-

ER2 207 mL Hepatocyte Specific Antigen Hep-Par1

OCH1E57 mL BRTU

PA0801

HIER

IVD

-

-

ER2 307 mL Mammaglobin (31A5 Rab) 'CM'

31A5

7 mL BRTU

PA0802

HIER

IVD

-

-

ER1 307 mL Microphthalmia Transcription Factor

C5/D5

7 mL BRTU

PA0803

HIER

IVD

-

-

ER2 207 mL Napsin A (MRQ-60 Mab) 'CM'

MRQ-60 Mab

7 mL BRTU

PA0805

HIER

IVD

-

-

ER2 207 mL p120 Catenin (MRQ-5 Mab) 'CM'

MRQ-5 Mab

7 mL BRTU

PA0806

HIER

IVD

-

-

ER2 207 mL PAX8 (MRQ-50 Mab) 'CM'

MRQ-50 Mab

7 mL BRTU

PA0808

HIER

IVD

-

-

ER2 107 mL Renal Cell Carcinoma (PN-15 Mab) CM

PN-15 Mab

7 mL BRTU

PA0811

EIER

IVD

-

-

ENZ 1 107 mL SOX-10 (Polyclonal) 'CM'

Polyclonal

7 mL BRTU

PA0813

HIER

IVD

-

-

ER2 207 mL SOX-2 (SP76 Rab) 'CM'

SP76 Rab

7 mL BRTU

PA0815

HIER

IVD

-

-

ER2 207 mL SOX-11 (MRQ-58 Mab) 'CM'

MRQ-58 Mab

7 mL BRTU

PA0816

HIER

IVD

-

-

ER2 207 mL PHH3 (Polyclonal) 'CM'

Polyclonal

7 mL BRTU

PA0817

HIER

IVD

-

-

ER2 207 mL IgG4 (MRQ-44 Mab) 'CM'

MRQ-44 Mab

7 mL BRTU

PA0818

EIER

IVD

-

-

ENZ 1 107 mL (4C4.9 MAB) S100 Protein 'CM'

4C4.9 MAB

7 mL BRTU

PA0820

HIER

IVD

-

-

ER1 10* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent
F Frozen P Paraffin O Other Applications W Western blotting BOND BOND Ready-to-Use format Liquid Liquid Concentrate format

152

IVD PROBES
11Q23 / DLEU157............................................................................ 158

CDKN2A / 9Q21 (TISSUE)57............................................................ 176

15Q22 / 6Q2157.............................................................................. 158

COL1A1 / PDGFB57......................................................................... 177

15Q22 / 9Q3457.............................................................................. 159

CRLF2 / IGH57................................................................................. 177

19Q13 / TP5357............................................................................... 159

CTNND257....................................................................................... 178

1Q21 / 8P2157................................................................................. 160

DDIT3 BREAK57............................................................................... 178

1Q21 / SRD57.................................................................................. 160

DEK / NUP21457.............................................................................. 179

20Q-57............................................................................................. 161

DIC(9;20)57...................................................................................... 179

5Q DUAL-COLOR57.......................................................................... 161

DIGEORGE II / SE 1057..................................................................... 180

5Q- TRIPLE-COLOR57....................................................................... 162

DLEU1 / 13QTER57.......................................................................... 180

6Q21 / MYC57.................................................................................. 162

DLEU1 / TP5357.............................................................................. 181

6Q21 / SE 657.................................................................................. 163

EGFR / SE 757.................................................................................. 181

7Q-57............................................................................................... 163

ELN / 7Q2257.................................................................................. 182

7Q- TRIPLE-COLOR57....................................................................... 164

ERBB2 / SE 1757.............................................................................. 182

ACRO-P-ARMS57.............................................................................. 164

ERCC1 / ZNF44357.......................................................................... 183

ALK / EML457.................................................................................. 165

ETV6 / RUNX157.............................................................................. 183

ALK BREAK57.................................................................................. 165

ETV6 BREAK57................................................................................ 184

AR / SE X57...................................................................................... 166

EWSR1 / NFATC57........................................................................... 184

ATM / GLI157................................................................................... 166

EWSR1 BREAK57............................................................................. 185

ATM / SE 1157................................................................................. 167

FGFR1 / SE 857................................................................................ 185

AURKA57......................................................................................... 167

FGFR1 BREAK57.............................................................................. 186

AURKB57......................................................................................... 168

FGFR2 / SE 1057.............................................................................. 186

BCL2 / IGH57................................................................................... 168

FGFR3 / IGH57................................................................................. 187

BCL2 / IGH (TISSUE)57.................................................................... 169

FGFR4 / 5Q11.257........................................................................... 187

BCL2 BREAK57................................................................................ 169

FIP1L1 / CHIC2 /PDGFRA DUAL-COLOR57....................................... 188

BCL2 BREAK (TISSUE)57................................................................. 170

FIP1L1 / CHIC2 /PDGFRA TRIPLE-COLOR57.................................... 188

BCL6 BREAK57................................................................................ 170

FOXO1 BREAK57.............................................................................. 189

BCL6 BREAK (TISSUE)57................................................................. 171

FUS BREAK57.................................................................................. 189

BCR / ABL157.................................................................................. 171

GATA4 / SE 857................................................................................ 190

BCR / ABL1 DC57............................................................................. 172

GLI1 / SE 1257................................................................................. 190

BCR / ABL1 DC ES57........................................................................ 172

HIRA / SHANK357............................................................................ 191

BCR / ABL1 TC57............................................................................. 173

IGF1R / 15Q1157............................................................................. 191

CBFB BREAK57................................................................................ 173

IGH BREAK57................................................................................... 192

CCND1 / IGH FUSION57................................................................... 174

IGH BREAK (TISSUE)57.................................................................... 192

CCND1 /SE 1157.............................................................................. 174

IRF4 / DUSP22 BREAK57................................................................. 193

CCND1 BREAK57............................................................................. 175

JAK2 BREAK57................................................................................ 193

CDK4 / SE 1257................................................................................ 175

KMT2A / AFF157............................................................................. 194

CDKN2A / 9Q2157........................................................................... 176

KMT2A / MLLT157........................................................................... 194

153

IVD PROBESKMT2A / MLLT357........................................................................... 195

ROS1 BREAK57................................................................................ 213

KMT2A / MLLT457........................................................................... 195

RUNX1 / RUNX1T157....................................................................... 214

KMT2A / SE 1157............................................................................. 196

SE 18 (D18Z1)57.............................................................................. 214

KMT2A BREAK57............................................................................. 196

SE 7 / SE 857................................................................................... 215

MAF/ IGH57..................................................................................... 197

SE X / SE Y57................................................................................... 215

MAFB /IGH57................................................................................... 197

SE X / SE Y / SE 1857....................................................................... 216

MALT1 BREAK57.............................................................................. 198

SHOX / SE X57................................................................................. 216

MALT1 BREAK (TISSUE)57............................................................... 198

SNRPN / PML57............................................................................... 217

MDM2 / SE 1257.............................................................................. 199

SRD / SE 157.................................................................................... 217

MDM4 / SE 157................................................................................ 199

SS18 BREAK57................................................................................ 218

MECOM BREAK57............................................................................ 200

STS / KAL1 / SE X57........................................................................ 218

MECOM BREAK TRIPLE-COLOR57.................................................... 200

TBX1 / SHANK357........................................................................... 219

MECOM/RUNX157........................................................................... 201

TERC / 3Q1157................................................................................ 219

MET / SE 757................................................................................... 201

TERC / MYC / SE 757....................................................................... 220

MM-BCR / ABL157........................................................................... 202

TERT / 5Q3157................................................................................. 220

MYC (8Q24) BREAK57...................................................................... 202

TERT / 5Q31 (TISSUE)57.................................................................. 221

MYC (8Q24) BREAK (TISSUE)57....................................................... 203

TFE3 BREAK57................................................................................. 221

MYC / SE 857................................................................................... 203

TMPRSS2-ERG57............................................................................. 222

MYC / IGH T(8;14) FUSION57........................................................... 204

TOP2A / ERBB2 / SE 1757................................................................ 222

MYCN / AFF357............................................................................... 204

TOP2A / SE 1757............................................................................. 223

MYEOV / IGH57................................................................................ 205

TP53 / ATM57.................................................................................. 223“N25” / SHANK357........................................................................... 205

TP53 / MPO57................................................................................. 224

NF1 / MPO57................................................................................... 206

TP53 / SE 1757................................................................................ 224

NSD1 / TERT57................................................................................ 206

TP53 / SE 17 (TISSUE)57................................................................. 225

NUP98 BREAK57.............................................................................. 207

UBE3A / PML57............................................................................... 225

PAFAH1B1 / 17P1157...................................................................... 207

WHSC1 / SE 457.............................................................................. 226

PDGFRB BREAK57........................................................................... 208

XIST / SE X57................................................................................... 226

PML / RARA57................................................................................. 208

ZNF217 / 20Q1157.......................................................................... 227

PPARG BREAK57.............................................................................. 209

SATELLITE ENUMERATION FISH PROBES (IVD)............................... 228

PTEN / SE 1057............................................................................... 209

WHOLE CHROMOSOME FISH PROBES (IVD).................................... 229

RARA BREAK57................................................................................ 210

SUB TELOMERIC FISH PROBES (IVD)............................................... 230

RB157.............................................................................................. 210
RB1 / RCAN157................................................................................ 211
RB1 / RCAN1, SE X/SE Y/ SE 1857................................................... 211
RCAN157......................................................................................... 212
RCAN1 / SE X / SE Y57..................................................................... 212
RET BREAK57.................................................................................. 213

154

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V

A

N

C

E

D

S

T

A

I

N

I

11q23 / DLEU1

N

G

-

I

V

D

P

R

O

B

E

15q22 / 6q21
11q23 / DLEU1 13q14 probehybridized to MM patientmaterial showing a 13q14
deletion (1R2G).

15q22 / 6q21 hybridized to
MM patient material withgain of both critical regions
6q21 and 15q22.

Image kindly provided by
Prof. Jauch, Heidelberg.

Image kindly provided by
Prof. Jauch, Heidelberg.

11q23 / DLEU1 (13q14)

15q22 / 6q21

CODE

COLOR

FORMATSTATUS

KBI-10502

Green/Red

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-10504

Green/Red

10 test

IVD

MENU

MENU

HEMATOPATHOLOGYHEMATOPATHOLOGYBACKGROUNDBACKGROUND

Hybridization results delineated 11q23 and 11q25 as the most frequently gained
regions in Multiple Myeloma (MM) which supports a relevant pathogenetic role ofgenes in this region. Deletions of 13q14 are frequently detected by interphase FISH
in patients with newly diagnosed MM, correlate with increased proliferative activity,
and represent an independent adverse prognostic feature in MM.

Chromosome 6q amplifications encompassing 6q21-22 have been observed in
MM including the same region as in CLL. Amplification including band 15q22 hasbeen reported in MM. The 15q22 specific FISH probe is optimized to detect copy
numbers at 15q22.
The 6q21 specific DNA region is optimized to detect copy numbers at 6q21.

The 11q23 specific FISH probe is optimized to detect copy numbers at 11q23. The
DLEU1 (13q14) specific DNA region is optimized to detect copy numbers of the
DLEU1 (previously known as DLEU) gene region at 13q14.

REFERENCES
Cremer et al, 2005, Genes Chrom Cancer, 44; 194-203.

REFERENCES
Gonzalez et al, 2004, Haematologica, 89; 1213-1218.
Cremer et al, 2005, Genes Chrom Cancer, 44; 194-203.

UT5980

RH99154

SEC63

RB1
650 kB
SHGC-155029

TRIM13DLEU1560 kB

11

D11S2076

D6S24615

230 kB

D13S272

ZBTB16
11q23

SMAD6
SHGC-154519

6q21

D13S1477
13q14

15q22

275 kB6450 kB

13

D13S25* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

155

540 kB

S

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N

C

E

D

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T

A

I

N

I

15q22 / 9q34

N

G

-

I

V

D

P

R

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B

E

19q13 / TP53
15q22 / 9q34 hybridized
to a normal interphase/
metaphase (2R2G).

19q13 / TP53 (17p13)
hybridized to patient material
showing a TP53 (17p13)
deletion (1R2G).

15q22 / 9q34

19q13 / TP53 (17p13)

CODE

COLOR

FORMATSTATUS

KBI-10508

Green/Red

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-10509

Green/Red

10 test

IVD

MENU

MENU

HEMATOPATHOLOGYHEMATOPATHOLOGYBACKGROUNDBACKGROUND

The hyperdiploid subtype in MM is defined by presence of multiple trisomic
chromosomes. Combination of the chromosome 9q34 and 15q22 specific regions
are important regions to detect the hyperdiploid subtype in MM which is usuallyassociated with a low frequency of IGH translocations.

TP53 (previously known as p53) gene deletion, which can be identified byinterphase FISH in almost a third of patients with newly diagnosed MM, is aprognostic factor predicting for short survival of MM patients treated withconventional-dose chemotherapy. Amplification of 19q13 has been reported ina variety of cancer. The 19q13 specific FISH probe is optimized to detect copy
numbers at 19q13.

The 15q22 and 9q34 FISH probe is designed as a dual-color assay to detect
amplifications at 15q22 and 9q34.

The TP53 (17p13) specific DNA region is optimized to detect copy numbers of the
TP53 gene region at 17p13.

REFERENCES
Cremer et al, 2005, Genes Chrom Cancer, 44; 194-203.

REFERENCES
Drach et al, 1998, Blood, 92; 802-809.
Cremer et al, 2005, Genes Chrom Cancer, 44; 194-203.

UT5980

SHGC-147754

15q22

SMAD6

17p13

540 kB

D17S960
RH55877

ASS1
430 kB

9q34

S

RH103512

SHGC-154519

CD37

335 kB15

19q13.3

TP53

D17S634

9

17

19

D19S1022* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

156

340 kB

A

D

V

A

N

C

E

D

S

T

A

I

N

I

1q21 / 8p21

N

G

-

I

V

D

P

R

O

B

E

S

1q21 / SRD
1q21 / 8p21 hybridized to anormal metaphase (2R2G).

1q21 / SRD (1p36)
hybridized to a normal
metaphase (2R2G).

1q21 / 8p21

1q21 / SRD (1p36)

CODE

COLOR

FORMATSTATUS

KBI-10503

Green/Red

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-10507

Green/Red

10 test

IVD

MENU

MENU

HEMATOPATHOLOGYHEMATOPATHOLOGYBACKGROUNDBACKGROUND

Amplifications of 1q21 are concurrent with dysregulated expression of MAF,
MMSET / FGFR3, or Deletion 13 and represent an independent unfavorable
prognostic factor. Allelic losses of the chromosome 8p21-22 have been reported
as a frequent event in several cancers.

Frequent loss of heterozygosity (LOH) on the short arm of chromosome 1 (1p)has been reported in a series of human malignancies. The combination with thepotentially amplified 1q21 region allows to detect deletions at 1p36 and gain of
1q21 in a single FISH assay.

The 1q21 specific FISH probe is optimized to detect copy numbers at 1q21. The
8p21 specific DNA region is optimized to detect copy numbers at 8p21.

The 1q21 specific FISH probe is optimized to detect copy numbers at 1q21. The
SRD 1p36 specific FISH probe is optimized to detect copy numbers of 1p at region
1p36 containing the markers D1S2795 and D1S253.

REFERENCESREFERENCES

Shaughnessy J., 2005, Hematology, 10 suppl, 1; 117-126.
Cremer et al, 2005, Genes Chrom Cancer, 44; 194-203.

Cremer et al, 2005, Genes Chrom Cancer, 44; 194-203.
Shaughnessy J., 2005, Hematology, 10 suppl, 1; 117-126..
D8S1066

8p21

PNOC

1p36.3205 kB

SHGC-149299

SHGC-56649

530 kB
CHD5
SHGC-108153

RH64628

350 kB

1q21

8
1q21

S100A10

RH64628

SHGC-144740

350 kB
S100A10
SHGC-144740

1
1* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

157

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V

A

N

C

E

D

S

T

A

I

N

I

20q-

N

G

-

I

V

D

P

R

O

B

E

S

5q Dual-Color
20q- (20q12) / 20q11 probehybridized to patient material
showing 20q- deletion(1R2G).

5q- (5q31; 5q33) probehybridized to patient material
showing a 5q33 deletion(1R2G).

Material kindly provided by
Labdia Labordiagnostik,
Vienna.

20q- (20q12) / 20q11

5q- (5q31; 5q33)

CODE

COLOR

FORMATSTATUS

KBI-10203

Green/Red

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-10209

Green/Red

10 test

IVD

MENU

MENU

HEMATOPATHOLOGYHEMATOPATHOLOGYBACKGROUNDBACKGROUND

Acquired deletions of the long arm of chromosome 20 are found in several
hematologic conditions and particularly in the myeloproliferative disorders (MPD)
and myelodysplastic syndromes and acute myeloid leukemia (MDS / AML). A
minimal critical region deleted in MPD and MDS has been identified at 20q12 which
includes a protein tyrosine phosphatase receptor gene.

The presence of del(5q), either as the sole karyotypic abnormality or as part ofa more complex karyotype, has distinct clinical implications for myelodysplastic
syndromes (MDS) and acute myeloid leukemia. Interstitial 5q deletions are themost frequent chromosomal abnormalities in MDS and are present in 10% to 15%
of MDS patients. Two different critical regions are described, one at 5q31-q33
containing the CSF1R and RPS14 gene regions, characteristic for the ‘5q-’
syndrome, and a more proximal located region at 5q13-q31 containing the CDC25C
and EGR1 gene regions.

The 20q- (20q12) specific FISH probe is optimized to detect copy numbers of
20q at region 20q12. A 20q11 region specific probe is included to facilitate
chromosome identification.

The 5q- specific FISH probe is optimized to detect copy numbers at the CDC25C/ EGR1 gene region at 5q31 and the CSF1R / RPS14 gene region at 5q33
simultaneously in a dual-color assay.

REFERENCES
Bench et al, 2000, Oncogene, 19; 3902-3913.
Asimakopoulos et al, 1994, Blood, 84; 3086-3094.

REFERENCES
Boultwood J e.a., Blood 2002, 99; 4638-4641.
Zhao N e.a., PNAS 1997, 94; 6948-6953.
Wang e.a., Haematologica 2008, 93; 994-1000.
Ebert BL e.a., Nature 2008, 451; 335-339.
Mohamedali A and Mufti GJ, Brit J Haematol 2008, 144; 157-168.

SHGC-144070

610 kB
MAPRE1
RH57467
20q11.2
20q12

20

STSG25365

PTPRT

370 kB

WI-2294

RH48032

CDC25C
EGR1

650 kB

SHGC-3896
5q31

5q33

D5S1907

CSF1R
RPS14

5

810 kB

D5S2014* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

158

A

D

V

A

N

C

E

D

S

T

A

I

N

I

5q- Triple-Color

N

G

-

I

V

D

P

R

O

B

E

6q21 / MYC
5q- (5q31; 5q33) / TERT
(5p15)Triple-Color probehybridized to a normal
metaphase (2R2G2B).

6q21 / MYC (8q24)
CODE

COLOR

FORMATSTATUS

KBI-10117

Green/Red

10 testIVD

MENU
HEMATOPATHOLOGYBACKGROUND
Deletions affecting the long arm of chromosome 6 (6q) involving band 6q21
are among the most commonly observed chromosomal aberrations in lymphoidmalignancies and have been identified as adverse prognostic factor in subsets oftumors. Amplification of MYC (8q24) has been described in many types of solid
tumors, such as breast, cervical and colon cancers, as well as in myeloma, nonHodgkin’s lymphoma, gastric adenocarcinomas and ovarian cancer.

5q- (5q31; 5q33) / TERT (5p15) Triple-Color
CODE

COLOR

FORMATSTATUS

KBI-10210

Green/Red/Blue

10 testIVD

MENU

The 6q21 / MYC (8q24) FISH probe is designed as a dual-color assay to detect
deletions and amplifications at 6q21 and 8q24.

HEMATOPATHOLOGYREFERENCESBACKGROUND

Zhang, Y, 2000, Genes, Chrom. And Canc. 27; 52-58.
Bentz, M et al, 1995, Blood, 85; 3610-3618.

The 5q- specific FISH probe is optimized to detect copy numbers at the CDC25C/ EGR1 gene region at 5q31 and the CSF1R / RPS14 gene region at 5q33
simultaneously in a dual-color assay. The triple-color probe provides in addition to
the two critical regions a control in blue targeting the TERT (previously known as
hTERT) gene region at 5p15.

SEC63

Boultwood J e.a., Blood 2002, 99; 4638-4641.
Zhao N e.a., PNAS 1997, 94; 6948-6953.
Wang e.a., Haematologica 2008, 93; 994-1000.
Ebert BL e.a., Nature 2008, 451; 335-339.
Mohamedali A and Mufti GJ, Brit J Haematol 2008, 144; 157-168.
5p15.3

SHGC-140056

RH99154

REFERENCES

275 kB

MYC

6q21
D6S246

8q24.28

D8S1720

6

SHGC-154319

TERT

390 kB

D5S2269E

RH48032

CDC25C
EGR1

650 kB

SHGC-3896
5q31

5q33

D5S1907

CSF1R
RPS14

5

810 kB

D5S2014* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

159

270 kB

S

A

D

V

A

N

C

E

D

S

T

A

I

N

I

6q21 / SE 6

N

G

-

I

V

D

P

R

O

B

E

S

7q6q21 / SE 6 probe hybridized
to a normal metaphase(2R2G).

7q- (7q22; 7q36) hybridized
to patient material showing a
7q36 deletion (1R2G).

Image kindly provided by
Prof. Jauch, Heidelberg.

6q21 / SE 6

7q- (7q22; 7q36)

CODE

COLOR

FORMATSTATUS

KBI-10105

Green/Red

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-10202

Green/Red

10 test

IVD

MENU

MENU

HEMATOPATHOLOGYHEMATOPATHOLOGYBACKGROUNDBACKGROUND

Deletions affecting the long arm of chromosome 6 (6q) are among the mostcommonly observed chromosomal aberrations in lymphoid malignancies and havebeen identified as an adverse prognostic factor in subsets of tumors including CLL.
A minimal deletion region has been identified within a 2-megabase segment of
6q21, between D6S447 and D6S246. The SEC63 gene is located within this criticalregion.

Loss of a whole chromosome 7 or a deletion of the long arm, del(7q), are recurring
abnormalities in malignant myeloid diseases. Most deletions are interstitial andthere are two distinct deleted segments of 7q. The majority of patients haveproximal breakpoints in bands q11-22 and distal breakpoints in q31-36. The CCAAT
displacement protein CUX1 gene region is located in the 7q22 critical region.
The 7q- specific FISH probe is optimized to detect copy number of 7q at 7q22 andat 7q36 simultaneously in a dual-color assay.

The 6q21 specific FISH probe is optimized to detect copy numbers of 6q at region
6q21.The chromosome 6 Satellite Enumeration FISH probe (SE 6) at D6Z1 isincluded to facilitate chromosome identification.

REFERENCES
LeBeau et al., 1996, Blood, 88; 1930-1935.
Doehner et al, 1998, Blood, 92; 4031-4035.

REFERENCES
Sherratt et al, 1997, Chromosome Res, 5; 118-124.
Zhang et al, 2000, Genes Chrom Cancer, 27; 52-58.

D7S2536

CUX1

D6Z1

RH99154

SEC63

7q22

520 kB

RH44454

275 kB
D7S2419

6q21

7q36

D6S246

7CUL1

330 kB

D7S2640

6* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

160

A

D

V

A

N

C

E

D

S

T

A

I

N

I

7q- Triple-Color

N

G

-

I

V

D

P

R

O

B

E

Acro-P-Arms
7q (7q22; 7q36) / SE 7
Triple-Color probe hybridized
to a normal metaphase(2R2G2B).

Acro-P-Arms NOR Blue
CODE

COLOR

FORMATSTATUS

KBI-20033B

Blue

10 testIVD

KBI-20033G

Green

10 testIVD

KBI-20033R

Red

10 testIVD

MENUCONSTITUTIONAL

7q- (7q22; 7q36) / SE7 Triple-Color
CODE

COLOR

FORMATSTATUS

KBI-10207

Green/Red/Blue

10 testIVD

BACKGROUND
The NOR (Nucleolar Organizer Region) is located on every p-arm of the humanacrocentric chromosomes. Enlargement of the acrocentric p-arms can be causedby an unusual variant or a translocation event. NOR stain of the p-arms is useful
to detect such a p-arm variant. In the classification of small supernumerarymarker chromosomes (SMCs) the Acro-P-Arms NOR FISH probe can detect theorigin of DNA, in which about 80% will turn out to be derived from the acrocentricchromosomes. The Acro-P-Arms NOR FISH probe is optimized to detect the short(p) arm of all acrocentric human chromosomes. The probe is intended to be usedon metaphase/interphase spreads.

MENU
HEMATOPATHOLOGYBACKGROUND
The 7q- specific FISH probe is optimized to detect copy number of 7q at
7q22 and at 7q36 simultaneously in a dual-color assay. The chromosome 7
Satellite Enumeration FISH probe (SE 7) at D7Z1 in blue is included to facilitate
chromosome identification.

REFERENCES
Starke H et al., 2003, Hum. Genet., 114; 51-67.
Starke H et al., 2005, J. Histochem Cytochem, 53; 359-360.

REFERENCES
LeBeau et al., 1996, Blood, 88; 1930-1935.
Doehner et al, 1998, Blood, 92; 4031-4035.

D7S2536

D7Z1

CUX1

7q22

520 kB

RH44454

D7S2419
7q36

7

CUL1

330 kB

D7S2640* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

161

S

A

D

V

A

N

C

E

D

S

T

A

I

N

I

ALK / EML4

N

G

-

I

V

D

P

R

O

B

E

ALK BreakHybridization of ALK EML4
fusion probe to a lungadenocarcinoma tissue
section showing normal
signal pattern (2R2G).

Hybridization of ALK
break probe to a lungadenocarcinoma tissue
section showing positivetranslocation signal(1RG1R1G).

ALK (2p23) / EML4 t(2;2) inv (2) Fusion

ALK (2p23) Break

CODE

COLOR

FORMATSTATUS

KBI-10746

Green/Red

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-10747

Green/Red

10 test

IVD

MENU

MENU

LUNG PATHOLOGYLUNG PATHOLOGYBACKGROUNDBACKGROUND

The inversion in 2p21 and 2p23 leading to a fusion of the kinase domain of ALK(anaplastic lymphoma kinase) and EML4 (echinoderm microtubule associatedprotein like 4) has been described in 5-7% of non-small cell lung cancer (NSCLC)
cases.

Translocations of the ALK (anaplastic lymphoma kinase) gene at 2p23 haveoriginally been associated with anaplastic lymphomas, B-cell lymphomas,
neuroblastomas and myofibroblastic tumors. At least 21 translocation partners
have been described, however 80% of the translocations involves the NPM1
gene (5q35). ALK rearrangements have been described in non-small cell lungcancer (NSCLC) cases. Multiple tyrosine kinsae inhibitors (TKI’s) specific for ALK
have since been approved for first line treatment of NSCLC-patients carrying thefusion gene ALK-EML4. These ALK inhibitors include crizotinib (Xalkori), alectinib(Alecensa) and ceritinib (Zykadia).

Multiple tyrosine kinsae inhibitors (TKI’s) specific for ALK have since been
approved for first line treatment of NSCLC-patients carrying the fusion gene ALKEML4. These ALK inhibitors include crizotinib (Xalkori), alectinib (Alecensa) andceritinib (Zykadia).
The ALK / EML4 t(2;2); inv(2) Fusion probe is designed as a dual-color assay todetect the fusion of the ALK gene with the EML4 gene by paracentric inversion withbreakage and reunion occurring at bands 2p21 and 2p23.

The ALK (2p23) Break probe is optimized to detect translocations involving the
ALK gene region at 2p23.
REFERENCESREFERENCES

Soda et al, Nature, 2007, 448, 561-566.
Kwak et al, J Clin Oncol., 27(26):4247-53.
Koivunen et al, Clin Cancer Res, 2008, 14, 4275-4283.

Soda et al, Nature, 2007, 448, 561-566.
Koivunen et al, Clin Cancer Res, 2008, 14, 4275-4283.

AFM347YA5

AFM347YA5

350 kB

2p23
SHGC-17159

ALK

350 kB

2p23
SHGC-17159
SHGC-83664

Gap: 12 MB

ALK

2p21

340 kB

SHGC-144661

SHGC-106023

350 kB
SHGC-104981

EML4

2

2

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

162

S

A

D

V

A

N

C

E

D

S

T

A

I

N

I

AR / SE X

N

G

-

I

V

D

P

R

O

B

E

ATM / GLI1
AR (Xq12) / SE X probehybridized to VCaP prostatecancer cell showing highlevel
AR gene amplification.

ATM (11q22) / GLI1 (12q13)
hybridized to a normal
metaphase (2R2G).

Image kindly provided by
Prof. Trapman, Erasmus
Medical Centre, Rotterdam.

AR (Xq12) / SE X

ATM (11q22) / GLI1 (12q13)

CODE

COLOR

FORMATSTATUS

KBI-10720

Green/Red

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-10108

Green/Red

10 test

IVD

MENU

MENU

UROPATHOLOGYHEMATOPATHOLOGYBACKGROUNDBACKGROUND

The androgen receptor (AR) gene has been identified as a target gene for the
Xq12 amplification found in one-third of hormone-refractory prostate cancers. The
findings suggest that AR gene amplification and overexpression is involved in theemergence of prostate cancer.

Deletion of ATM at 11q22-q23 indicates a rather poor prognosis, amplificationof GLI1 (previously known as GLI) at 12q13 is associated with an intermediate
prognosis. The ATM (11q22) specific FISH probe is optimized to detect copy
numbers of the ATM gene region at 11q22.

The AR (Xq12) FISH probe is optimized to detect copy numbers of the AR generegion at region Xq12. The chromosome X satellite enumeration probe (SE X) at
DXZ1 is included to facilitate chromosome identification.

The GLI1 (12q13) specific FISH probe is optimized to detect copy numbers of the
GLI1 gene region at 12q13.
REFERENCESREFERENCES

Doehner H et al, 1997, Blood, 7; 2516-2522.
Boultwood J, 2001, J. Clin. Pathol., 54; 512-516.
Dierlamm J et al, 1998, Genes Chromosomes Cancer, 20; 155-166.
Doehner H at al, 1999, J. Molec. Med., 77; 266-281.

Visakorpi T et al, 1995, Nat. Genet. 9; 401-406.
Koivisto P et al, 1997, Cancer Res. 57 ; 314-319.

D12S1266

DXZ1
Xq12

D11S4485

781E8LEAR

12q13

270 kB
GLI1

340 kBATM

2684LE

11q22

235 kB

RH75890

RH39918

X

11

12* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

163

S

A

D

V

A

N

C

E

D

S

T

A

I

N

I

ATM / SE 11

N

G

-

I

V

D

P

R

O

B

E

S

AURKA
ATM (11q22) / SE 11
hybridized to patient material
showing a 11q22 deletion at
the ATM gene region (1R2G).

AURKA (20q13) / 20q11
probe hybridized tocolorectal carcinoma
material showing
amplification of AURKA,
gene region at 20q13.

Image kindly provided by Dr.
Wenzel, Basel.

Material kindly provided by
Dr. Carvalho, Amsterdam.

ATM (11q22) / SE 11

AURKA (20q13) / 20q11

CODE

COLOR

FORMATSTATUS

KBI-10103

Green/Red

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-10721

Green/Red

10 test

IVD

MENU

MENU

HEMATOPATHOLOGYUROPATHOLOGYBACKGROUNDBACKGROUND

Chromosome 11q22.3-23.1 deletions involving the ataxia-teleangiectasia mutated(ATM) locus are detected at diagnosis in 15-20% of cases of B-cell chronic
lymphocytic leukemia (CLL) and are associated with a relatively aggressive
disease. Loss of the 11q22-23 region, where the ataxia-telangiectasia mutated(ATM) gene is located, is also one of the most frequent secondary chromosomal
aberrations in mantle cell lymphoma.

Aurora kinase A (AURKA) gene amplification has been detected in approximately
12% of primary breast tumors, as well as in bladder, ovarian, colon, prostate,neuroblastoma and cervical cancer cell lines. The AURKA (20q13) / 20q11 probe isdesigned to detect copy numbers of the AURKA gene region at region 20q13.
The AURKA (20q13) FISH probe is optimized to detect copy numbers of the AURKA
gene region at region 20q13. The 20q11 specific DNA probe is included to facilitate
chromosome identification.

The ATM (11q22.3) specific FISH probe is optimized to detect copy numbers of the
ATM gene region at region 11q22.3. The chromosome 11 Satellite Enumeration (SE11) at D11Z1 FISH probe is included to facilitate chromosome identification.

REFERENCES
Uchida et al, 2010, Cancer Genet Cytogenet 203; 324-327.
Sen et al, 2002, J of Nat Canc Inst 94; 1320-1329.
Lassmann et al, 2007, Clin Cancer Res 13; 4083-4091.

REFERENCES
Doehner et al, 1997, Blood, 89; 2516-2522.
Bigoni et al, 1997, Leukemia, 11; 1933-1940.

SHGC-144070

MAPRE1610 kB

D11Z1
D11S448520q11.2

ATM
11q22

235 kB

20

RH39918

RH57467

20q13.2
SHGC-12066

AURKA

11

490 kB

RH75698* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

164

A

D

V

A

N

C

E

D

S

T

A

I

N

I

AURKB

N

G

-

I

V

D

P

R

O

B

E

S

BCL2 / IGH
AURKB (17p13) / SE 17
probe hybridized to tumor
tissue (2R2G).

BCL2 / IGH t(14;18) probehybridized to a normalinterphase/metaphase(2R2G).

AURKB (17p13) / SE 17

BCL2 / IGH t(14;18) Fusion

CODE

COLOR

FORMATSTATUS

KBI-10722

Green/Red

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-10606

Green/Red

10 test

IVD

MENU

MENU

TUMOR DIFFERENTIATIONHEMATOPATHOLOGYBACKGROUNDBACKGROUND

Aurora kinase B (AURKB) localizes to microtubules, and is a key regulator of themitotic cell division and chromosome segregation processes. Gain of functionof AURKB correlates with cell proliferation, induction of multinuclear cells, andchromosomal instability.

The t(14;18) chromosomal translocation is a common cytogenetic abnormality inhuman lymphoma and is observed in about 85% of follicular lymphoma (FL) and up
to one-third of diffuse lymphomas (DL). Two breakpoint region clusters (brc) havebeen identified: a major breakpoint region (mbr) within the 3’ untranslated regionof the BCL2 proto-oncogene (approximately 60% of the cases) and a minor cluster
region (mcr) 30 kb 3’ of BCL2 ( approximately 25%).

The significant interest of the gene in cancer diagnostics is related to thedriving function of AURKB in tumor progression, histological differentiation, andmetastasis. AURKB is predictive for the aggressive recurrence of many different
types of tumors, including hepatocellular carcinoma and oral squamous cell
carcinoma.

The BCL2 / IGH t(14;18)(q21;q32) specific FISH probe is optimized to detect thereciprocal translocation t(18;14), involving either of the two brc in the BCL2 genein a dual-color, dual-fusion assay. Kreatech has optimized this FISH probe for the
specific use on cell material (KBI-10606), or on tissue (KBI-10755).

The AURKB (17p13) FISH probe is optimized to detect copy numbers of the AURKB
gene region at region 17p13. The Chromosome 17 Satellite Enumeration (SE 17)
probe at D17Z1 is included to facilitate chromosome identification.

REFERENCES
Poetsch et al, 1996, J Clin Oncol, 14; 963-969.
Vaandrager et al, 2000, Genes Chrom Cancer, 27; 85-94.

REFERENCES
Smith et al, 2005, Br J Cancer, 93; 719-729.

RH75060
D14S683E

RH54968

BCL2

17p13

D17Z1

18q21

AURKB

IGH
510 kB

1420 kB

18

SHGC-4651

14q32

RH36627

14

RH6679017* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

165

1270 kB

A

D

V

A

N

C

E

D

S

T

A

I

N

I

BCL2 / IGH (tissue)

N

G

-

I

V

D

P

R

O

B

E

S

BCL2 BreakBCL2/IGH t(14;20) Fusion
Probe hybridized to paraffin
embedded lymph nodematerial (2R2G).

BCL2 (18q21) Break probehybridized to a normal
metaphase.

Image kindly provided by
P. May, Imperial College,
Hammersmith Hospital,
LondonBCL2 / IGH t(14;18) Fusion (tissue)

BCL2 (18q21) Break

CODE

COLOR

FORMATSTATUS

KBI-10755

Green/Red

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-10612

Green/Red

10 test

IVD

MENU

MENU

HEMATOPATHOLOGYHEMATOPATHOLOGYBACKGROUNDBACKGROUND

Follicular lymphoma is a mature B-Cell lymphoma, characterized by the presenceof the t(14;18) translocation that juxtaposes the BCL2 locus on chromosome
18q21 to the immunoglobulin H (IGH) locus on chromosome 14q32, resulting in theoverexpression of the antiapoptotic protein BCL2.

Follicular lymphoma is a mature B-cell lymphoma characterized by the presence ofthe t(14;18) translocation that juxtaposes the BCL2 locus on chromosome 18q21
to the immunoglobulin H (IGH) locus on chromosome 14q32, resulting in theoverexpression of the anti-apoptotic protein BCL2. Next to IGH, other translocation
partners to BCL2 are also known (e.g. IGK at 2p11.2 and IGL at 22q11). A breakor split assay is therefore best suited to detect rearrangements of the BCL2 generegion at 18q21.

The BCL2 / IGH t(14;18) Fusion probe is optimized to detect the reciprocaltranslocation t(14;18) in a dual-color, dual-fusion assay on formalin fixed paraffin
embedded tissue samples. In addition Kreatech has developed a probe for the
specific use on cell material (KBI-10606).

The BCL2 (18q21) Break FISH probe is optimized to detect translocations
involving the BCL2 gene region at 18q21 in a dual-color, split assay on metaphase/interphase spreads, bloodsmears and bone marrow cells.

REFERENCES
Taniwaki M et al, 1995, Blood, 86; 1481-1486.
Poetsch M et al, 1996, J Clin Oncol, 14; 963-969.

REFERENCES
Taniwaki M et al, 1995, Blood, 86; 1481-1486.
Poetsch M et al, 1996, J Clin Oncol, 14; 963- 969.
Einerson R et al, 2005, Am J Clin Pathol, 124; 421-429.

RH75060
D14S683E

BCL21270 kB

18q21

IGH

RH75060

1420 kB

18

480 kB

SHGC-4651

D18S91

BCL2

14q32

14

18q21

RH66790

D18S87540 kB18

SHGC-4651* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

166

A

D

V

A

N

C

E

D

S

T

A

I

N

I

BCL2 Break (tissue)

N

G

-

I

V

D

P

R

O

B

E

S

BCL6 BreakBCL2 (18q21) Breakhybridized to paraffin
embedded tissue (2RG).

BCL6 (3q27) Break probehybridized to patient material(1RG1R1G).

Image kindly provided by
Prof. Siebert, Kiel.

BCL2 (18q21) Break (tissue)

BCL6 (3q27) Break

CODE

COLOR

FORMATSTATUS

KBI-10745

Green/Red

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-10607

Green/Red

10 test

IVD

MENU

MENU

HEMATOPATHOLOGYHEMATOPATHOLOGYBACKGROUNDBACKGROUND

Follicular lymphoma is a mature B-cell lymphoma characterized by the presenceof the t(14;18) translocation that juxtaposes the BCL2 locus on chromosome
18q21 to the immunoglobulin H (IGH) locus on chromosome 14q32, resulting in
the overexpression of the anti-apoptotic protein BCL2. Besides IGH, additionaltranslocation partners to BCL2 have been identified. A break or split assay istherefore best suited to detect rearrangements of the BCL2 gene region at 18q21.

Chromosomal translocations involving band 3q27 with various different partner
chromosomes represent a recurrent cytogenetic abnormality in B-cell nonHodgkin’s lymphoma. Kreatech has developed this probe for the specific use
on cell material (KBI-10607), or on tissue (KBI-10730). Two different breakpoint
regions have been identified; the major breakpoint region (MBR) is located within
the 5’ noncoding region of the BCL6 proto-oncogene, while the atypical breakpoint
region (ABR) is located approximately 200 kb distal to the BCL6 gene.

The BCL2 (18q21) Break probe is optimized to detect translocations involving the
BCL2 gene region at 18q21 in a dual-color, split assay on paraffin embedded tissue
sections.

The BCL6 (3q27) Break FISH probe is designed in a way to flank both possible
breakpoints, thereby providing clear split signals in either case.

Kreatech has developed this probe for the specific use on cell material (KBI10612), or on tissue (KBI-10745).

REFERENCES
Butler et al, 2002, Cancer Res, 62; 4089-4094.
Sanchez-Izquierdo, 2001, Leukemia, 15; 1475-1484.

REFERENCES
Taniwaki M et al, 1995, Blood, 86; 1481-1486.
Poetsch M et al, 1996, J Clin Oncol, 14; 963- 969.
Einers R et al, 2005, Am J Clin Pathol, 124; 421-429.
RH75060

480 kB

D3S4060

D18S91

BCL2
18q21

540 kB

D18S87540 kB18

SHGC-143921

BCL6

SHGC-4651

MBR*
ABR*

SHGC-60245

410 kB

3q27

3

SHGC-7226

ABR* atypical breakpoint region
MBR* major breakpoint region* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
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A

D

V

A

N

C

E

D

S

T

A

I

N

I

BCL6 Break (tissue)

N

G

-

I

V

D

P

R

O

B

E

S

BCR / ABL1
Hybridization of BCL6 breakprobe to a tissue section
showing aberrant pattern(1RG1R1G).

BCR / ABL1 t(9;22) Fusion
probe hybridized on patientmaterial showing t(9;22)(q34;q11) reciprocaltranslocation (2RG1R1G).

Image kindly provided by
Monika Conchon, São Paulo.

BCL6 (3q27) Break (tissue)

BCR / ABL1 t(9;22) Fusion

CODE

COLOR

FORMATSTATUS

KBI-10730

Green/Red

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-10005

Green/Red

10 testIVD

KBI-12005

Green/Red

20 testIVD

MENU
HEMATOPATHOLOGYMENUHEMATOPATHOLOGYBACKGROUNDBACKGROUND

Chromosomal translocations involving band 3q27 with various different partner
chromosomes represent a recurrent cytogenetic abnormality in B-cell nonHodgkin’s lymphoma. Kreatech has developed this probe for the specific use on
cell material (KBI-10607), or on tissue (KBI-10730).

The BCR / ABL1 t(9;22) Fusion FISH probe is optimized to detect the t(9;22)(q34;q11) reciprocal translocation in a dual-color, dual-fusion assay on metaphase/interphase spreads, blood smears and bone marrow cells.

Two different breakpoint regions have been identified; the major breakpoint region(MBR) is located within the 5’ noncoding region of the BCL6 proto-oncogene, while
the atypical breakpoint region (ABR) is located approximately 200 kb distal to
the BCL6 gene. The BCL6 (3q27) Break probe is designed to flank both possible
breakpoints, thereby providing clear split signals.

This probe will also detect cryptic insertions of ABL1 (previously known as ABL)
into the BCR region not detectable by karyotyping and therefore described as Phnegative.
REFERENCES
Morris et al, 1990, Blood, 76; 1812-1818.
Dewald et al, 1998, Blood, 91; 3357-3365.
Kolomietz et al, 2001, Blood, 97; 3581-3588.
Huntly et al, 2003, Blood, 102; 1160-1168.
Tkachuk et al., 1990, Science, 250; 559-562.

The BCL6 (3q27) Break probe is optimized to detect translocations involving the
BCL6 gene region at 3q27 in a dual-color, split assay on paraffin-embedded tissue
sections.
REFERENCES
Butler et al, 2002, Cancer Res, 62; 4089-4094.
Sanchez-Izquierdo, 2001, Leukemia, 15; 1475-1484.

D22S940
SHGC-147754

IGLL5

ASS1
ABL1

22q11.2

1050 kB

BCR

22
NUP2149q34

9D3S4060

D9S1991

IGLL1
SHGC-107450

540 kB
SHGC-143921

BCL6

MBR*
ABR*

SHGC-60245

410 kB

3q27

3

SHGC-7226

ABR* atypical breakpoint region
MBR* major breakpoint region* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

1681030 kB

A

D

V

A

N

C

E

D

S

T

A

I

N

I

BCR / ABL1 DC

N

G

-

I

V

D

P

R

O

B

E

S

BCR / ABL1 DC ES
BCR / ABL1 t(9;22),
Dual-Color, Single-Fusion
probe hybridized to patientmaterial showing t(9;22)translocation (1RG1R1G).

BCR / ABL1 t(9;22),
Dual-Color, Single-Fusion
probe hybridized to patientmaterial showing t(9;22)translocation (1RG1R1G).

Material kindly provided by
Dr. Balogh, Budapest.

Material kindly provided by
Dr. Balogh, Budapest.

BCR / ABL1 t(9;22) Dual-Color, Single-Fusion

BCR / ABL1 t(9;22) Dual-Color, Single-Fusion, Extra Signal

CODE

COLOR

FORMATSTATUS

KBI-10009

Green/Red

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-10008

Green/Red

10 test

IVD

MENU

MENU

HEMATOPATHOLOGYHEMATOPATHOLOGYBACKGROUNDBACKGROUND

A simple dual-color, single-fusion assay is preferably used for the initial screeningof CML and ALL patients. The Philadelphia chromosome, der(22q), is visualized
by a fusion signal while the der(9q) shows no signal. The BCR / ABL1 t(9;22) FISH
probe is optimized to detect the t(9;22)(q34;q11) reciprocal translocation in a dualcolor, single-fusion assay on metaphase/interphase spreads, blood smears andbone marrow cells.

A simple dual-color, single-fusion assay is preferably used for the initial screeningof CML and ALL patients. The Philadelphia chromosome, der(22q), is visualized
by a fusion signal while the der(9q) shows no signal. The BCR / ABL1 t(9;22) FISH
probe is optimized to detect the t(9;22)(q34;q11) reciprocal translocation in a dualcolor, single-fusion, extra-signal assay on metaphase/interphase spreads, bloodsmears and bone marrow cells.

REFERENCESREFERENCES

Morris et al, 1990, Blood, 76; 1812-1818.
Dewald et al, 1998, Blood, 91; 3357-3365.
Kolomietz et al, 2001, Blood, 97; 3581-3588.
Huntly et al, 2003, Blood, 102; 1160-1168.
Tkachuk et al., 1990, Science, 250; 559-562.

Morris et al, 1990, Blood, 76; 1812-1818.
Dewald et al, 1998, Blood, 91; 3357-3365.
Kolomietz et al, 2001, Blood, 97; 3581-3588.
Huntly et al, 2003, Blood, 102; 1160-1168.
Tkachuk et al., 1990, Science, 250; 559-562.

D22S940

RH63154

ABL1

NUP214
9q34

RH27788

ABL1

BCR
620 kB

IGLL5

ASS1

345 kB
22q11.2

D22S940

SHGC-147754

IGLL5

ASS1

22

425 kB
22q11.2
SHGC-107331

1050 kB

BCR

22
NUP214

IGLL1
9q34

D9S1991

9IGLL1

D9S19919* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

169

A

D

V

A

N

C

E

D

S

T

A

I

N

I

BCR / ABL1 TC

N

G

-

I

V

D

P

R

O

B

E

S

CBFB BreakBCR / ABL1 t(9;22),TripleColor, Dual Fusion
probe hybridized on
patient material showing
translocation of distal BCR(1BG1RB1R1G).

Hybridization of CBFB
break probe to a metaphasespread showing normal
pattern (2RG).

Image kindly provided by
Prof. Siebert, Kiel.

BCR / ABL1 t(9;22) Triple-Color, Dual-Fusion

CBFB t(16;16), inv(16) Break

CODE

COLOR

FORMATSTATUS

KBI-10006

Green/Red/Blue

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-10304

Green/Red

10 test

IVD

MENU

MENU

HEMATOPATHOLOGYHEMATOPATHOLOGYBACKGROUNDBACKGROUND

The BCR / ABL1 t(9;22) FISH probe is a triple-color, dual-fusion probe built fromthe same regions as the dual-color, dual-fusion probe, but the proximal BCR regionis labeled in blue. Using the triple-color probe allows to distinguish between thederivative chromosome 22, the Philadelphia chromosome, which will be observed
as purple (red/blue) color, while the derivative chromosome 9 will show a yellow(red/green) signal.

Inv(16)(p13;q22) and t(16;16)(p13;q22) are recurring chromosomal rearrangements
in AML. In both the inversion and translocation, the critical genetic event is thefusion of the CBFB gene at 16q22 to the smooth muscle myosin heavy chain(MYH11) at 16p13. A deletion of between 150 and 350 kb centromeric to the p-arm
inversion breakpoint cluster region can be observed in some patients containing
the 5’ portion of the myosin heavy chain (MYH11) gene.

REFERENCES

The CBFB t(16;16) inv(16) break FISH probe is optimized to detect the inversionof chromosome 16 involving the CBFB gene region at 16q22 in a dual-color, split
assay.

Morris et al, 1990, Blood, 76; 1812-1818.
Dewald et al, 1998, Blood, 91; 3357-3365.
Kolomietz et al, 2001, Blood, 97; 3581-3588.
Huntly et al, 2003, Blood, 102; 1160-1168.
Tkachuk et al., 1990, Science, 250; 559-562.

REFERENCES
Dauwerse et al, 1993, Hum.Mol.Genet., 2; 1527-1534.
Marlton et al, 1995, Blood, 85; 772-779.
D22S940

SHGC-147754

IGLL5

ASS1
ABL1

1050 kB

NUP2149

D9S1991

275 kB
RH54691

RH27788

CBFB

BCR

22
9q34

RH113713

345 kB
22q11.2

D16S2846

SHGC-170333

335 kB

16q22

IGLL1

535 kB

16

SHGC-107450

RH32600* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
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170

A

D

V

A

N

C

E

D

S

T

A

I

N

I

CCND1 / IGH Fusion

N

G

-

I

V

D

P

R

O

B

E

S

CCND1 /SE 11
CCND1 / IGH t(11;14) Fusion
probe hybridized to a normalinterphase/metaphase(2R2G).

CCDN1 (11q13) / SE 11
probe hybridized to patientinterphases / metaphaseshowing CCDN1 (11q13)
amplification with polyploidy
for chromosome 11.

CCND1 / IGH t(11;14) Fusion

CCND1 (11q13) / SE 11

CODE

COLOR

FORMATSTATUS

KBI-10604

Green/Red

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-10734

Green/Red

10 test

IVD

MENU

MENU

HEMATOPATHOLOGYTUMOR DIFFERENTIATIONBACKGROUNDBACKGROUND

Mantle cell lymphoma is a subtype of non-Hodgkin lymphoma characterized
by poor prognosis. Cytogenetically t(11;14) is associated with 75% of mantle
cells lymphomas. The translocation breakpoints are scattered within the 120 kb
region adjacent to CCND1 (previously known as BCL1). The translocation leads
to overexpression of cyclin D1 due to juxtaposition of the Ig heavy chain geneenhancer on 14q32 to the cyclin D1 gene on 11q13.

The binding of cyclin D1 (also named CCND1 or BCL1) to cyclin-dependent
kinases (CDKs) leads to the phosphorylation of retinoblastoma protein (pRb),
subsequently triggering the release of E2F transcription factors to allow G1 to S
phase progression of the cell cycle. Consistent with this function, overexpressionof cyclin D1 results in a more rapid progression from the G1 to S phase transition
and in a reduced serum dependency in fibroblast cells, characteristics typicallyseen in cancer cells. The CCND1 (11q13) FISH probe is optimized to detect
copy numbers of the CCND1 gene region at region 11q13. The Chromosome 11
Satellite Enumeration (SE 11) probe at D11Z1 is included to facilitate chromosome
identification.

The CCND1 / IGH t(11;14)(q13;q32) specific FISH probe is optimized to detect thereciprocal translocation t(11;14) in a dual-color, dual-fusion assay.
REFERENCESREFERENCES

Vaandrager et al, 1996, Blood, 88; 1177-1182.

Okami et al, 1999, Oncogene 18; 3541-3645.
Freier et al, 2003, Cancer Res; 1179-1182.

RH52377
D14S683E

MYEOV

11q13

CCND1

IGH

1200 kB

1420 kB
D11Z1

FGF4
FGF3
RH4810914q32

14RH103547
RH66790

11q13

CCND1
530 kB

1111

SHGC-147246* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
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171

A

D

V

A

N

C

E

D

S

T

A

I

N

I

CCND1 Break

N

G

-

I

V

D

P

R

O

B

E

S

CDK4 / SE 12
CCND1 (11q13) Break probehybridized to a normal
metaphase (2R2G).

CDK4 (12q13) / SE 12 probehybridized to liposarcoma
tissue showing multiple
amplification involving the
CDK4 gene region at 12q13(3+R2G).

Image kindly provided by Dr.
Sapi, Hungary.

CCND1 (11q13) Break

CDK4 (12q13) / SE 12

CODE

COLOR

FORMATSTATUS

KBI-10609

Green/Red

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-10725

Green/Red

10 test

IVD

MENU

MENU

HEMATOPATHOLOGYSOFT TISSUE PATHOLOGYBACKGROUNDBACKGROUND

Overexpression of the Cyclin D1 gene caused by amplification or translocation
is described for several types of cancer. A t(11;14) is the main characteristic
aberration in mantle cell lymphoma (documented in 40-70% of the cases. In MM,
the same translocation t(11;14)(q13:q32) is the most common, with a reported
frequency of 15% to 20% of the cases.

Amplification of the CDK4 gene region at 12q13-q15 has been observed in several
types of cancer, especially in gliomas and sarcomas. CDK4 codes for a cyclin
dependent kinase which is involved in controlling progression through the G1
phase of the cell cycle. The oncogenic potential of CDK4 activation has been
related to the deregulation of the G1 phase by increasing the hyperphosphorylationof retinoblastoma tumor suppressor protein helping to cancel its growth-inhibitory
effects.

Kreatech has developed this probe to detect rearrangements of the CCND1
gene region at 11q13 (KBI-10609) or for the translocation t(11;14) in Mantle Cell
Lymphoma (KBI-10604) and for MM (KBI-10605). The CCND1 (11q13) Break FISH
probe is optimized to detect translocations involving the CCND1 gene region at
11q13 in a dual-color, split assay on metaphase/interphase spreads.

The CDK4 (12q13) FISH probe is optimized to detect copy numbers of the CDK4
gene region at 12q13. The chromosome 12 satellite enumeration probe (SE 12) at
D12Z3 is included to facilitate chromosome identification.

REFERENCESREFERENCES

Vaandrager et al, 1996, Blood, 88; 1177-1182.
Vaandrager et al, Blood, 89; 349-350.

Kuhnen et al, 2002, Virchows Arch 441 ; 299-302.
Shimada et al, 2006, Hum Path 37(9) ; 1123-1129.

RH102068

D12Z3

510 kB

D12S1266

RH103450

12q13

MYEOV
11q13

CDK4

CCND1

900 kB

RH67810FGF4
FGF3

550 kB

D12S1529

SHGC-144332

12

11* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

172

A

D

V

A

N

C

E

D

S

T

A

I

N

I

CDKN2A / 9q21

N

G

-

I

V

D

P

R

O

B

E

S

CDKN2A / 9q21 (tissue)
CDKN2A (9p21) / 9q21
hybridized to a metaphasespread showing a normal
pattern (2R2G).

CDKN2A (9p21) / 9q21
(tissue) probe hybridized totissue (2R2G).

CDKN2A (9p21) / 9q21

CDKN2A (9p21) / 9q21 (tissue)

CODE

COLOR

FORMATSTATUS

KBI-10402

Green/Red

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-10710

Green/Red

10 test

IVD

MENU

MENU

HEMATOPATHOLOGYUROPATHOLOGYBACKGROUNDBACKGROUND

Hemizygous deletions and rearrangements of chromosome 9, band p21 areamong the most frequent cytogenetic abnormalities detected in pediatric acutelymphoblastic leukemia (ALL). This deletion includes loss of the CDKN2A(previously known as p16, INK4A or MTS1) / CDKN2B (previously known as p15,
INK4B or MTS2) genes, which are cell cycle kinase inhibitors and important inleukemogenesis.

Homozygous and hemizygous deletions of 9p21 are the earliest and most common
genetic alteration in bladder cancer. The CDKN2A (INK4A) gene has been identified
as tumor suppressor gene in this region which is commonly deleted in bladdercancer. The loss of DNA sequences on chromosomal bands 9p21-22 has been
documented also in a variety of malignancies including leukemias, gliomas, lungcancers, and melanomas. The CDKN2A (9p21) FISH probe is optimized to detect
copy numbers of the CDKN2A gene region at region 9p21. The 9q21 region probe isincluded to facilitate chromosome identification.

The CDKN2A (9p21) specific FISH probe is optimized to detect copy numbers of
the CDKN2A gene region at region 9p21. The 9q21 region probe is included tofacilitate chromosome identification.

REFERENCES
Stadler et al, 1994, Cancer Res, 54:2260-2063.
Williams et al, 1995, Hum Mol Genet; 4: 1569-1577.

REFERENCES
Dreyling et al, 1995, Blood, 86; 1931-1938.
Southgate et al, 1995, Br J Cancer, 72; 1214-1218.

D9S1749

CDKN2A(p16)

D9S1749

CDKN2A
(p16)
9p21

9p21

350 kB

D9S975

CDKN2B(p15)
D9S9759q21

350 kBCDKN2B(p15)

9q21

RH40366

440 kB
PIP5K1B

RH40366

440 kB

SHGC-82248

9

PIP5K1B
SHGC-82248

9* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

173

A

D

V

A

N

C

E

D

S

T

A

I

N

I

COL1A1 / PDGFB

N

G

-

I

V

D

P

R

O

B

E

CRLF2 / IGH
Interphase FISH result of
COL1A1/PDGFB Fusion
probe hybridized todermatofibrosarcoma
protuberans tumor tissue,
showing co-localization andamplification of the fusion
gene.

Hybridization of CRLF2
break / IGH fusion probe to a
metaphase spread showing
normal pattern (2RG2B).

COL1A1 / PDGFB t(17;22) Dual-Color, Single-Fusion

CRLF2 (Xp22 / Yp11) Break / IGH (14q32) Fusion, Triple-Color

CODE

COLOR

FORMATSTATUS

KBI-10742

Green/Red

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-10406

Green/Red/Blue

10 test

IVD

MENU

MENU

SOFT TISSUE PATHOLOGYHEMATOPATHOLOGYBACKGROUNDBACKGROUND

The diagnosis of primary soft tissue and bone tumors is often challenging as
they are relatively rare. The misdiagnosis between dermatofibroma (DF) anddermatofibrosarcoma protuberans (DFSP) or giant cell fibroblastoma (GCF)
might result in incorrect primary management. DFSP and GCF have in most cases
diagnosed today a translocation involving the COL1A1 (collagen, type I, alpha 1)gene at 17q21 and the PDGFB (platelet-derived growth factor beta polypeptide)
gene at 22q13. Also, a supernumerary ring chromosome derived from thetranslocation t(17;22) can be present.

CRLF2-IGH fusions between Xp22-14q32 or Yp11-14q32 results in a deregulated
expression of the cytokine receptor gene (CRLF2). This can also be the result of
the fusion with the P2RY8 promoter on Xp22 or Yp11.
Gain of chromosome X has been observed in Down syndrome-associated ALL.
The CRLF2 (Xp22 / Yp11) Break / IGH (14q32) Fusion Triple-Color FISH probe is
optimized to detect translocations involving the CRLF2 gene at region Xp22 andYp11. The probe shows a break between red and green in case of a translocation
with CRLF2 and IGH involvement. In case of a fusion with the P2RY8 gene on Xp22
or Yp11, one red probe is deleted. For fusion confirmation to the IGH gene, a blue
probe covering IGH is added.

The COL1A1 / PDGFB t(17;22) Dual-Color Single-Fusion probe is optimized todetect the t(17;22)(q21;q13) involving the COL1A1 (17q21) and PDGFB (22q13)
gene regions in dual-color, single-fusion assay on paraffin embedded tissue
sections.

REFERENCES
Mullighan et al., 2009, Nat. Genet. 41(11): 1243-1246.
Russell et al., 2009, Blood, 114(13): 2688-2698.

REFERENCES
Maire et al, 2007, Arch Dermatol, 143; 203-210.
Labropoulos et al, 2007, Biologics, 1; 347-353.
Patel et al, 2008, Hum Path, 39; 184-193.
Sandberg, 2003, Cancer Genet Cytogenet, 140; 1-12.

AFMA284XC9
D14S683E

Xp22.3/Yp11.3

360 kB
G66032

IGH
D22S1139

COL1A1700 kB

22q13

530 kB
RH45275

1420 kB

CRLF2

GGAT3F08Y

325 kB

14q32

RH93128

17q21

S

22

14

RH66350

RH66790P2RY8

DXYS138

HUMUT1411

PDGFB

X

17

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

174

A

D

V

A

N

C

E

D

S

T

A

I

N

I

CTNND2

N

G

-

I

V

D

P

R

O

B

E

S

DDIT3 BreakCri-Du-Chat CTNND2 (5p15)/ 5q31 probe hybridized to anormal metaphase 2RG).

DDIT3 (12q13) Break probehybridized to a normal
metaphase (2RG).

DDIT3 (12q13) BreakCri-Du-Chat CTNND2 (5p15) / 5q31
CODE

COLOR

FORMATSTATUS

KBI-40106

Green/Red

10 testIVD

KBI-45106

Green/Red

5 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-10714

Green/Red

10 test

IVD

MENU
MENU

SOFT TISSUE PATHOLOGYPOSTNATALBACKGROUNDBACKGROUND

Liposarcoma is one of the most frequent sarcomas in adults, representing 10
to 16 percent of soft tissue sarcomas. Most patients with round cell/myxoid
liposarcoma have an acquired t(12;16)(DDIT3-FUS) or t(12;22)(DDIT3-EWS)
translocation, both of which involve the DDIT3 gene at 12q13. A break or split
probe for DDIT3 is best used to analyze translocation of the DDIT3 (12q13) gene onformalin fixed paraffin embedded tissue for routine clinical diagnosis.

Cri-Du-Chat syndrome is an autosomal deletion syndrome caused by a partial
deletion of chromosome 5p. It is characterized by a distinctive, high-pitched,catlike cry in infancy with growth failure, microcephaly, facial abnormalities, andmental retardation throughout life. Loss of a small region in band 5p15.2 (Cri-DuChat critical region) correlates with all the clinical features of the syndrome withthe exception of the catlike cry, which maps to band 5p15.3 (catlike cry criticalregion).

The DDIT3 (12q13) Break probe is optimized to detect translocations involving the
DDIT3 gene region at 12q13 in a dual-color, break assay.

The Cri-Du-Chat region probe is optimized to detect copy numbers at the CTNND2
gene region in the Cri-Du-Chat critical region at 5p15.2. The 5q31 specific FISH
probe is included as control probe.

REFERENCES
Panagopoulos et al, 1994, Cancer Res, 54; 6500-6503.
Schoenmakers et al, 1994, Genomics, 20; 210-222.

REFERENCES
Overhauser et al, 1994, Hum. Mol. Genet., 3; 247-252.
Gersh et al, 1997, Cytogenet Cell Genet., 77; 246-251.

RH75353

700 kB
RH48794
12q13

DDIT3
RH44152

SHGC-107760
5p15.2680 kB

CTNND2
RH118682

570 kB

12

D5S2874

RH48032

CDC25C
650 kB

5q31

EGR1
SHGC-3896

5* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

175

A

D

V

A

N

C

E

D

S

T

A

I

N

I

DEK / NUP214

N

G

-

I

V

D

P

R

O

B

E

S

dic(9;20)
Hybridization of DEK/
NUP214 Fusion Probe to a
positive cell line showing afusion due to t(6;9).

dic(9;20) Triple-Color.

Image kindly provided by Dr.
Ann Nordgren, Stockholm.

DEK / NUP214 t(6;9) Fusion

dic(9;20) Triple-Color

CODE

COLOR

FORMATSTATUS

KBI-10306

Green/Red

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-10405

Green/Red/Blue

10 test

IVD

MENU

MENU

HEMATOPATHOLOGYHEMATOPATHOLOGYBACKGROUNDBACKGROUND

The chromosomal translocation t(6;9) (p22;q34) is associated with a specificsubtype of acute myeloid leukemia (AML) and constitutes 0.5% to 4% of all AML
cases. The translocation results in a fusion between the DEK oncogene (6p22)
and the nucleoporin 214 kDa (NUP214 at 9q34; previously known as CAN). The
exact mechanism by which the fusion protein DEK-NUP214 contributes to leukemia
development has not been identified. Patients with t(6;9) AML have a very poor
prognosis.

The dic(9;20)(p13.2;q11.2) is a recurrent chromosomal abnormality in pediatric
Bcell precursor acute lymphoblastic leukemia (BCP-ALL), which occurs in ~2%of the cases. It is associated with an intermediate outcome with relapses being
relatively frequent, compared to other common cytogenetic subgroups of BCP-ALL(e.g. high hyperploidy and t(12;21)). The dic(9;20) is an unbalanced rearrangement
involving chromosomes 9 and 20, resulting in the co-localisation of the respective
centromeres and concomitant loss of the chromosome arms 9p and 20q.

The DEK / NUP214 t(6;9) specific FISH probe has been optimized to detect thereciprocal translocation t(6;9) in a dual-color, dual-fusion assay on metaphase/interphase spreads, blood smears and bone marrow cells.

The dic(9;20) Triple-Color FISH probe is optimized to detect the dicentric (9;20)(p13.2;q11.2) in a triple-color assay on metaphase/interphase spreads, bloodsmears and bone marrow cells.

REFERENCESREFERENCES

Von Lindern et al, 1992, Mol. Cell. Biol.,12; 1687-1697.
Ageberg et al, 2008, Gen. Chrom. Canc., 47; 276-287.
Chi et al, 2008, Arch. Pathol. Lab. Med., 132; 1835-1837.

Forestier et al., Genes Chromosome Cancer, 2008, 47; 149-158.
Pichler H et al., Br J Haematol, 2010, 149; 93-100.
Schmiegelow K et al., Leukemia, 2010, 24; 345-54.
Zachariadis V et al., Leukemia, 2011, 25; 22-628.
Zachariadis V et al., Br J Haematol, 2012, 159; 488-491.

RH102047
6p22

DEK

RH12467

D9S1201320 kB

ABL1
NUP214(CAN)

SHGC-79367

360 kB
1030 kB

D9Z1

20p11.2
RH92647

9q34

9SHGC-148792

20

6

20q11.2
RH428099
330 kB
D20S494* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
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A

D

V

A

N

C

E

D

S

T

A

I

N

I

DiGeorge II / SE 10

N

G

-

I

V

D

P

R

O

B

E

S

DLEU1 / 13qter
DiGeorge II(10p14) / SE 10
probe hybridized to DiGeorge
II patient material showing adeletion of the DGSII region
at 10p14 (1R2G).

DLEU1 (13q14) / 13qter
probe hybridized to patientmaterial showing a 13q14
deletion (1R2G).

Image kindly provided byAzzedine Aboura, Hôpital
Robert Debré Paris.

Image kindly provided by Dr.
Dastugue, Toulouse.

DLEU1 (13q14) / 13qter

DiGeorge II (10p14) / SE 10
CODE

COLOR

FORMATSTATUS

KBI-40105

Green/Red

10 testIVD

KBI-45105

Green/Red

5 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-10102

Green/Red

10 test

IVD

MENU
MENU

HEMATOPATHOLOGYPOSTNATALBACKGROUNDBACKGROUND

Deletions of chromosome 13q14 have been reported not only in CLL but in a varietyof human tumors, including other types of lymphoid and myeloid tumors, as wellas prostate, head and neck, and non-small cell lung cancers. The deletion of 13q
may be limited to a single locus (13q14), or accompanied with the loss of a larger
interstitial region of the long arm of chromosome 13. A minimal critical region of
400 kb has been described containing the DLEU1, DLEU2 and RFP2 genes.

DiGeorge and VCFS present many clinical problems and are frequently associatedwith deletions within 22q11.2, but a number of cases have no detectable molecular
defect of this region. A number of single case reports with deletions of 10p
suggest genetic heterogeneity of DiGeorge syndrome. FISH analysis demonstrates
that these patients have overlapping deletions at the 10p13 / 10p14 boundary.
The shortest region of deletion overlap (SRO) has been identified in a 1 cM interval
including makers D10S547 and D10S585.

The DLEU1 (13q14) specific FISH probe is optimized to detect copy numbers of
the DLEU1 (previously known as DLEU) gene region at 13q14. The 13qter (13q34)
region is included to facilitate chromosome identification.

The DiGeorge II region probe is optimized to detect copy numbers of the DGSII at
10p14. The chromosome 10 satellite enumeration (SE 10) FISH probe at D10Z1 isincluded to facilitate chromosome identification.

REFERENCES
Wolf et al, 2001, Hum Mol Genet, 10; 1275-1285.
Corcoran et al, 1998, Blood, 91; 1382-1390.

REFERENCES
Monaco et al, 1991, Am. J. Med. Genet., 39; 215-216.
Schuffenhauer et al, 1998, Eur. J. Hum. Genet., 6; 213-225.

RB1
650 kB
D13S1477

TRIM13
10p14

DLEU1

SHGC-82096
DGSII

230 kB

D13S272350 KB

13q14

D10Z1

D13S25450 kB

RH45055
RH66174

TFDP1
GAS6
13q34

13

1000 kB

RASA3
RH17923

10* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
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D

V

A

N

C

E

D

S

T

A

I

N

I

DLEU1 / TP53

N

G

-

I

V

D

P

R

O

B

E

S

EGFR / SE 7
DLEU1 (13q14) / TP53(17p13) hybridized to anormal metaphase (2R2G).

EGFR (7p11) / SE 7
hybridized to colon tissue(2R2G).

DLEU1 (13q14) / TP53 (17p13)

EGFR (7p11) / SE 7

CODE

COLOR

FORMATSTATUS

KBI-10113

Green/Red

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-10702

Green/Red

10 test

IVD

MENU

MENU

HEMATOPATHOLOGYLUNG PATHOLOGYBACKGROUNDBACKGROUND

Deletion of DLEU1 (previously known as DLEU) at 13q14 indicates a rather good
prognosis, deletion of TP53 (previously known as p53) at 17p13 is associated withpoor prognosis. The DLEU1 (13q14) specific FISH probe is optimized to detect
copy numbers at the DLEU1 gene region at 13q14. The TP53 (17p13) specific FISH
probe is optimized to detect copy numbers of the TP53 gene region at 17p13
REFERENCES

Epidermal growth factor receptor (EGFR) is a cell membrane protein, providing
signal transduction and cell growth. It is a member of the Erb-B family of type I
receptor tyrosine kinases and implicated in the development and progression of
non-small cell lung carcinomas (NSCLC), breast, intestine, and other organs. EGFR
has been found to act as a strong prognostic indicator in head and neck, ovarian,cervical, bladder and oesophageal cancers. In these cancers, increased EGFR
expression was associated with reduced recurrence-free or overall survival.

Amiel A et al, 1997, Cancer Gener.Cytogenet, 97; 97-100.
Drach J et al, 1998, Blood, 92; 802-809.
Stilgenbauer S et al, 1998, Oncogene, 16; 1891 - 1897.
Wolf S et al, 2001, Hum. Molec. Genet., 10; 1275-1285.

The EGFR (7p11) FISH probe is optimized to detect copy numbers of the EGFR
gene region at region 7p11. The chromosome 7 satellite enumeration (SE 7) probeat D7Z1 is included to facilitate chromosome identification.
REFERENCES

17p13

RB1

D17S960

Wang et al, 1993, Jpn J Hum Genet, 38: 399-406.
Nicholoset al, 2001, Eur J Cancer, 37: 9-15.

650 kB335 kB

D13S1477
13q14

TRIM13DLEU1

TP53

230 kB

D13S272

D17S634
RH10585817
450 kB13

7p11.2

D13S25

D7Z1

EGFR

340 kB

D7S2357

7* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
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178

A

D

V

A

N

C

E

D

S

T

A

I

N

I

ELN / 7q22

N

G

-

I

V

D

P

R

O

B

E

S

ERBB2 / SE 17
Williams-Beuren ELN (7q11)/ 7q22 probe hybridized to anormal metaphase (2RG).

ERBB2 (17q12) / SE 17 probehybridized to breast tumor
tissue showing amplificationof ERBB2 / SE 17.

Williams-Beuren ELN (7q11) / 7q22

ERBB2 (17q12) / SE 17

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KBI-40111

Green/Red

10 testIVD

KBI-10701

Green/Red

10 testIVD

KBI-45111

Green/Red

5 testIVD

KBI-14701

Green/Red

50 test

IVD

MENU

MENU

POSTNATAL

BREAST PATHOLOGYBACKGROUNDBACKGROUND

Williams-Beuren syndrome (WS) is characterized by cardiovascular disease,distinctive facial features, connective tissue abnormalities, mental retardation andendocrine abnormalities. Over 99% of individuals with the clinical diagnosis of
WS have this contiguous gene deletion, that encompasses the elastin (ELN) generegion including ELN, LIMK1, and the D7S613 locus.

The ERBB2 (or HER2) gene encodes a receptor tyrosine kinase involved in growth
factor signaling. Overexpression of this gene is seen in about 20% of invasive
breast cancers. ERBB2 gene amplification is a permanent genetic change that
results in this continuous overexpression of ERBB2. Trastuzumab (commonly
known as Herceptin) has been developed to be effective against ERBB2-positive
breast cancer. ERBB2 amplification is also observed in a variety of other tumors,such as gastric, prostate, lung, colon and ovary carcinoma.

The Williams-Beuren region probe is optimized to detect copy numbers of the ELN
gene region at 7q11. The 7q22 region specific FISH probe at 7q22 is included ascontrol probe.
REFERENCES

The ERBB2 (17q12) FISH probe is optimized to detect copy numbers of the ERBB2
gene region at region 17q12. The chromosome 17 satellite enumeration probe (SE17) at D17Z1 is included to facilitate chromosome identification/enumeration.

Ewart, et al, 1993, Nat. Genet., 5; 11-16.
Botta et al, 1999, J. Med. Genet., 36; 478-480.

REFERENCES
Pauletti et al, 1996, Oncogene, 13: 63-72.
Xing et al, 1996, Breast Cancer Res Treat, 39: 203-212.

SWSS2677

ELN
LIMK1

D17Z1

415 kB

SHGC-85693

17q12

CLIP2

ERBB2
460 kB

7q11.2
BV005603

17

7q22
AFM353TC9

7

CUX1

D17S1179

520 kB

RH44454* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
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179

A

D

V

A

N

C

E

D

S

T

A

I

N

I

ERCC1 / ZNF443

N

G

-

I

V

D

P

R

O

B

E

S

ETV6 / RUNX1
ERCC1 (19q13) / ZNF443(19p13) probe hybridized toparaffin embedded tissue(2R2G).

ETV6 / RUNX1 t(12;21)
Fusion probe hybridized topatient material showingt(12;21)translocation(2RG1R1G).

Material kindly provided by
Dr. Balogh, Budapest.

ERCC1 (19q13) / ZNF443 (19p13)

ETV6 / RUNX1 t(12;21) Fusion

CODE

COLOR

FORMATSTATUS

KBI-10739

Green/Red

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-10401

Green/Red

10 test

IVD

MENU

MENU

LUNG PATHOLOGYHEMATOPATHOLOGYBACKGROUNDBACKGROUND

Excision repair cross-complementing rodent repair deficiency, complementationgroup 1 (ERCC1) is a critical gene in the Nucleotide excision repair pathway.
A growing list of reports links cisplatin, carboplatin, and oxaliplatin based
chemotherapy resistance to ERCC1 expression levels in several tumors. ERCC1
has been shown to be an important marker to predict responsiveness to cisplatinbased chemotherapy. Low ERCC1 gene expression correlates with prolonged
survival after cisplatin-based chemotherapy.

The t(12;21), a cryptic translocation rarely observed by conventional cytogenetics,
was first identified by fluorescence in situ hybridization (FISH). In ALL blasts, thistranslocation fuses the 5’ part of the ETV6 (previously known as TEL) gene withalmost the entire RUNX1 (previously known as AML) (CBFA2) gene, producing thechimeric transcript ETV6-CBFA2. The t(12;21) (p13;q22) has also been identified
as the most frequent chromosomal abnormality in childhood ALL, affecting 20% to
25% of B-lineage cases.

The ERCC1 (19q13) FISH probe has been optimized to detect copy numbers of the
ERCC1 gene region at 19q13. The ZNF443 (19p13) probe is included to facilitate
chromosome identification.

The ETV6 / RUNX1 t(12;21) specific FISH probe is optimized to detect thereciprocal translocation t(12;21) (p13;q22) in a dual-color, dual-fusion assay.
REFERENCESREFERENCES

Romana et al, 1995, Blood, 85; 3662-3670.

Olaussen et al, 2006, N. Engl. J. Med. 335; 983-991.
Ceppi et al, 2006, Ann. Oncol. 17; 1818-1825.

12p13

D21S325
RH39900

D19S1025

ZNF443ETV6(TEL)

490 kB

21q22

1200 kB21

19p13.2
D19S671E

RUNX1(AML1)

SHGC-9898

RH76656

12

SHGC-5877
19q13.3

19

460 kB
RH47033

ERCC1* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
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1801380 kB

A

D

V

A

N

C

E

D

S

T

A

I

N

I

ETV6 Break

N

G

-

I

V

D

P

R

O

B

E

S

EWSR1 / NFATCETV6 (12p13) Break probehybridized to patient material
showing a translocation
involving the ETV6 region at
12p13 (1RG1R1G).

FISH result of the EWSR1/NFATC2 t(20;22) DC,
S-Fusion probe.

Image kindly provided by
Magret Ratjen, Kiel.

ETV6 (12p13) BreakEWSR1 / NFATC2 t(20;22) Dual-Color, Single-Fusion

CODE

COLOR

FORMATSTATUS

KBI-10403

Green/Red

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-10751

Green/Red

10 test

IVD

MENU

MENU

HEMATOPATHOLOGYSOFT TISSUE PATHOLOGYBACKGROUNDBACKGROUNDETV6 (previously known as TEL) gene is the abbreviation for -ETS variant 6- gene.
It encodes an ETS family factor which functions as a transcriptional repressor inhematopoiesis and in vascular development. The gene is located on chromosome
12p13, and is frequently rearranged in human leukemias of myeloid or lymphoidorigins. Also systematic deletion of the normal ETV6 allele in patients with ETV6RUNX1 fusions can be found. The ETV6 Break FISH probe is optimized to detect
translocations involving the ETV6 region at 12p13 in a dual-color, split assay on
metaphase/interphase spreads and bone marrow cells.

Ewing’s sarcoma is the second most frequent primary bone cancer. In most casesa translocation involving the EWSR1 gene at 22q12 and the FLI1 gene at 11q24 isobserved. Several other translocation partners of the ETS gene family can also be
involved. The first non-ETS family translocation partner described is the NFATC2
gene (nuclear factor of activated T-cells, cyto-plasmic, calcineurin-dependent 2) at
20q13.
The EWSR1 / NFATC2 t(20;22) Dual-Color Single-Fusion probe is optimized todetect the t(20;22)(q13;q12) involving the NFATC2 (20q13) and EWSR1 (22q12)
gene regions in a dual-color, single fusion assay on paraffin embedded tissue
sections.

REFERENCES
Golub et al, 1995, PNAS 92; 4917-4921.
Ford et al, 2001, Blood 98; 558-564.

REFERENCES
Szuhai et al, 2009, Clin Cancer Res, 15; 2259-2268.
Zucman-Rossi et al, 1998, PNAS, 95; 11786-11791.
Bernstein et al, 2006, Oncologist, 11; 503-519.

12p13
RH39900

500 kB
RH91343

ETV6
RH53036

RH65799

RH120772

SHGC-105635

750 kB

550 kB

480 kB

22q12

20q13.2

12

20

D22S448EWSR1

NFATC2
D20S857

22* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
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181

A

D

V

A

N

C

E

D

S

T

A

I

N

I

EWSR1 Break

N

G

-

I

V

D

P

R

O

B

E

FGFR1 / SE 8
EWSR1 (22q12) breakprobe hybridized to a tissue
section showing co-localized
and split signals.

FGFR1 gene locus
amplification in FFPE tissue
showing an amplification of
FGFR1 gene region at 8p11.

EWSR1 (22q12) BreakFGFR1 (8p11) / SE 8

CODE

COLOR

FORMATSTATUS

KBI-10750

Green/Red

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-12754

Green/Red

20 test

IVD

MENU

MENU

SOFT TISSUE PATHOLOGYLUNG PATHOLOGYBACKGROUNDBACKGROUND

Ewing’s sarcoma is the second most frequent primary bone cancer. In most casesa translocation involving the EWSR1 gene at 22q12 and the FLI1 gene at 11q24 areobserved, but several other translocation partners (ERG, ETV1, FEV, and E1A3) can
also be involved.

Amplification of the fibroblast growth factor receptor type 1 gene (FGFR1) has
been observed in numerous cancer types including lung cancer (especiallysquamous cell carcinoma) and breast cancer. With the development of new
therapeutic strategies, FGFR1 amplification could act as a valuable biomarker for
R&D and provide an attractive tool for clinical stratification. The FGFR1 (8p11) /SE 8 FISH probe is optimized to detect amplification involving the FGFR1 generegion at 8p11 in a dual-color assay on paraffin embedded tissue sections. The
chromosome 8 satellite enumeration probe (SE 8) at D8Z1 is included to facilitate
chromosome identification.

The EWSR1 (22q12) Break probe is optimized to detect translocations involving
the EWSR1 gene region at 22q12 in a dual-color, split assay on paraffin embedded
tissue sections.
REFERENCESREFERENCES

Zucman-Rossi, et al, 1998, PNAS, 95; 11786-11791.
Bernstein et al, 2006, Oncologist, 11; 503-519.

Weiss et al, 2010, Sci Transl. Med. 2(62); 62ra93.
Brooks et al, 2012, Clin. Cancer res. 18(7): 1855-62

RH120772

750 kB
RH46977

22q12

D22S448

8p11.2

EWSR1

SHGC-103388

22

D22S1554SE8

425 kB

FGFR1

540 kB

D8S4148* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
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182

S

A

D

V

A

N

C

E

D

S

T

A

I

N

I

FGFR1 Break

N

G

-

I

V

D

P

R

O

B

E

S

FGFR2 / SE 10
FGFR1 (8p11) Break probehybridization to a tissue
section showing a normal
pattern.

FGFR2 (10q26) / SE 10
CODE

COLOR

FORMATSTATUS

KBI-10757

Green/Red

10 testIVD

MENU
LUNG PATHOLOGYBACKGROUND
It is well documented that dysregulation of FGF-FGFR signaling via amplification,
point mutation or translocations may have an important role in tumor development
and progression. Alterations in FGFRs are associated with a number of humancancers, including lung, myeloma, breast, gastric, colon, bladder, pancreatic, andhepatocellular carcinomas. A growing body of preclinical data demonstrates
that inhibition of FGFR signaling can result in antiproliferative and/or pro-apoptic
effects, thus confirming the validity of the FGFR / FGFR axis as a potential
therapeutic target.

FGFR1 (8p11) Break
CODE

COLOR

FORMATSTATUS

KBI-10737

Green/Red

10 testIVD

MENU
BREAST PATHOLOGYThe FGFR2 (10q26) FISH probe is optimized to detect copy numbers of the FGFR2
gene region at region 10q26. The Chromosome 10 Satellite Enumeration (SE) probe
is included to facilitate chromosome identification.

BACKGROUNDFGFR1 has been implicated in the tumorigenesis of haematological malignancies,
where it is frequently involved in balanced chromosomal translocations,
including cases of chronic myeloid leukemia (BCR-FGFR1 fusion) and the 8p11
myeloproliferative syndrome/stem cell leukemia-lymphoma syndrome, which
is characterized by myeloid hyperplasia and non-Hodgkin’s lymphoma withchromosomal translocations fusing several genes, the most common being
a fusion between ZNF198 and FGFR1. The FGFR1 (8p11) Break FISH probe is
optimized to detect translocations involving the FGFR1 gene region at 8p11 in adual-color assay on FFPE tissue sections.

REFERENCES
Brooks et al, Clin Cancer Res. 2012; 18:1855.
Dutt et al, PLoS ONE 6: e2035.1
Kunii et al, Cancer Res. 2008; 68:2340-8.
Liang et al, Clin Cancer Res. 2013;19: 2572
Liao et al, Cancer Res. 2013;73:5195-205.
Weiss et al, Sci Transl Med. 2010; 2:62ra93.

REFERENCES
Smedley et al, 1998, Hum Mol Genet., 7; 627-642.
Sohal et al, 2001, Genes Chrom. Cancer, 32; 155-163.
Kwak et al, J Clin Oncol., 27(26); 4247-53.

D10Z1

RH103611

FGFR2
RH62328
10q26

520 kB108p11.2415 kB

RH76128

RH7851FGFR1
SHGC-103442

420 kB
SHGC-2804

8* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
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183

A

D

V

A

N

C

E

D

S

T

A

I

N

I

FGFR3 / IGH

N

G

-

I

V

D

P

R

O

B

E

S

FGFR4 / 5q11.2
FGFR3 / IGH t(4;14) Fusion
probe hybridized to MM
patient material showingt(4;14) translocation(2RG1R1G).

FGFR4 (5q35) / 5q11.2
CODE

COLOR

FORMATSTATUS

KBI-10756

Green/Red

10 testIVD

MENU
LUNG PATHOLOGY
Image kindly provided by
Prof. Jauch, Heidelberg.

BACKGROUND
It is well documented that dysregulation of FGF-FGFR signaling via amplification,
point mutation or translocations may have an important role in tumor development
and progression. Alterations in FGFRs are associated with a number of humancancers, including lung, myeloma, breast, gastric, colon, bladder, pancreatic, andhepatocellular carcinomas. A growing body of preclinical data demonstrates
that inhibition of FGFR signaling can result in antiproliferative and/or pro-apoptic
effects, thus confirming the validity of the FGFR / FGFR axis as a potential
therapeutic target.

FGFR3 / IGH t(4;14) Fusion
CODE

COLOR

FORMATSTATUS

KBI-10602

Green/Red

10 testIVD

MENU
HEMATOPATHOLOGYThe FGFR4 (5q35) FISH probe is optimized to detect copy numbers of the FGFR4
gene region at region 5q35. The 5q11.2 probe is included to facilitate chromosome
identification.

BACKGROUND
The t(4;14) translocation is undetectable by conventional cytogenetics. The
breakpoints on chromosome 4 occur within an approximately 113-kb region
located in small part of a conserved gene cluster including the transforming acidic
coiled-coil protein 3 (TACC3), fibroblast growth factor receptor 3 (FGFR3), andmultiple myeloma SET domain-containing protein (MMSET). The translocation isindicative for poor survival and poor response to chemotherapy.

REFERENCES
Brooks et al, Clin Cancer Res. 2012; 18:1855.
Dutt et al, PLoS ONE 6: e2035.1
Kunii et al, Cancer Res. 2008; 68:2340-8.
Liang et al, Clin Cancer Res. 2013;19: 2572
Liao et al, Cancer Res. 2013; 73:5195-205.
Weiss et al, Sci Transl Med. 2010; 2:62ra93.

The FGFR3 / IGH t(4;14)(p16;q32) Fusion specific FISH probe is optimized to detect
the reciprocal translocation t(4;14) in a dual-color, dual-fusion assay.
REFERENCES

HUMC5360

ISL1

Chesi et al, 1997, Nat Genet, 16; 260-264.
Finelli et al, 1999, Blood, 94; 724-732.

4p16

440 kB
5q11.2
D5S1395

RH46284

D4S992

D14S683E
D5S2703

WHSC1

150 kB

FGFR4

FGFR3

BAC51977S

1200 kB

IGH

1420 kB

5q35

NSD1

5
14q32

D4S43

14

RH667904* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

184

A

D

V

A

N

C

E

D

S

T

A

I

N

I

FIP1L1 / CHIC2 /PDGFRA Dual-Color

N

G

-

I

V

D

P

R

O

B

E

S

FIP1L1 / CHIC2 /PDGFRA Triple-ColorFIP1L1 / CHIC2 / PDGFRA(4q12) Deletion, Breakprobe hybridized to a normalinterphase/metaphase(2RG).

FIP1L1 / CHIC2 / PDGFRA(4q12) Deletion, Break
Triple-ColorFIP1L1 / CHIC2 / PDGFRA (4q12) Deletion, BreakFIP1L1 / CHIC2 / PDGFRA (4q12) Deletion, Break, Triple-Color

CODE

COLOR

FORMATSTATUS

KBI-10003

Green/Red

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-10007

Green/Red/Blue

10 test

IVD

MENU

MENU

HEMATOPATHOLOGYHEMATOPATHOLOGYBACKGROUNDBACKGROUND

The deletion of the CHIC2 locus generates a fusion FIP1L1-PDGFRA gene giving
raise to a novel tyrosine kinase. This deletion has been observed in patients with
idiophatic hypereosinophilic syndrome (HES), chronic eosinophilic leukemia (CEL),
systemic mast cell disease, and chronic myeloproiferative disorders (CMPD).

The FIP1L1 / CHIC2 / PDGFRA Triple-Color FISH probe is optimized to detect theCHIC2 deletion at 4q12 associated with the FIP1L1 / PDGFRA fusion in a triplecolor, split assay. It also allows the detection of translocation involving the FIP1L1
and PDGFRA region.

The FIP1L1 / CHIC2 / PDGFRA FISH probe is optimized to detect the CHIC2
deletion at 4q12 associated with the FIP1L1 / PDGFRA fusion in a Dual-Color,
split assay. It also allows the detection of translocation involving the FIP1L1 andPDGFRA region. However, chromosome 4 polyploidy may provide additional signals
not associated with a translocation involving 4q12.

Cools et al, N Engl J Med, 2003, 348; 1201-1214.
Griffin et al, 2003, PNAS, 100;7830-7835.
Gotlib et al, 2004, Blood, 103;2879-2891

REFERENCESREFERENCES

SHGC-68563

SCFD2

Cools et al, N Engl J Med, 2003, 348; 1201-1214.
Godlib et al, Blood, 2004, 103; 2879-2891.

640 kB

FIP1L1
4q12

RH65011

LNX1

D4S461

CHIC2

SHGC-68563

SCFD2

PDGFRAFIP1L1
4q12

SHGC-85185

520 kB

RH65011LNX1KIT

D4S461

CHIC2

460 kB

SHGC-50149

640 kB

SHGC-50170

460 kB

4

SHGC-50149

PDGFRA

SHGC-85185

520 kBKITSHGC-50170

4* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
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185

A

D

V

A

N

C

E

D

S

T

A

I

N

I

FOXO1 Break

N

G

-

I

V

D

P

R

O

B

E

S

FUS BreakFOXO1 (13q14) Break probehybridized to patient material(2RG).

FUS (16p11) Break probehybridized to liposarcoma
material.

FOXO1 (13q14) BreakFUS (16p11) Break

CODE

COLOR

FORMATSTATUS

KBI-10716

Green/Red

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-10715

Green/Red

10 test

IVD

MENU

MENU

SOFT TISSUE PATHOLOGYSOFT TISSUE PATHOLOGYBACKGROUNDBACKGROUND

The t(2;13) is associated with alveolar rhabdomyo-sarcomas. This translocation
results in the formation of a chimeric transcript consisting of the 5’ portion of
PAX3, including an intact DNA-binding domain fused to the FOXO1 gene on
chromosome 13. The t(1;13)(p36;q14) also seen in alveolar rhabdomyosarcomas
results in the fusion of another member of the PAX family, PAX7 to the FOXO1 geneon chromosome 13.

The fused in sarcoma (FUS) gene was originally shown to be rearranged in myxoid
liposarcomas harboring a t(12;16)(q13;p11) translocation. FUS has also beenshown to be involved in other recombinations: with ERG in acute myeloid leukemia
carrying a t(16;21), with ATF1 in band 12q13 in angiomatoid fibrous histiocytoma,
and with CREB3L2 in fibromyxoid sarcoma.
A break or split probe for FUS is best used to analyze translocation of the FUS(16p11) gene on formalin fixed paraffin embedded tissue for routine clinicaldiagnosis.

A break or split probe for FOXO1 is best used to analyze translocation of the
FOXO1 (13q14) gene on formalin fixed paraffin embedded tissue for routine clinicaldiagnosis.

The FUS (16p11) Break probe is optimized to detect translocations involving the
FUS gene region at 16p11 in a dual-color, split assay on metaphase/interphasespreads and paraffin embedded tissue sections.

The FOXO1 (13q14) Break probe is optimized to detect translocations involving the
FOXO1 gene region at 13q14 in a dual-color, split assay on metaphase/interphasespreads and paraffin embedded tissue sections.

REFERENCESREFERENCES

Shing et al, 2003, Cancer Res, 63: 4568-4576.
Storlazzi et al, 2003, Hum. Mol. Genet., 12: 2349-2358.

Barr et al, 1996, Hum. Mol. Genet., 5; 15-21.
Coignet et al, 1999, Genes Chrom. Cancer, 25; 222-229.

D16S2574E

780 kB

RH45178850 kB

16p11.2

RH53132

FUS

13q14

SHGC-106097

FOXO1

550 kB

RH1427716

690 kB

13

RH47854

D16S2933E

D13S1050* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
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186

A

D

V

A

N

C

E

D

S

T

A

I

N

I

GATA4 / SE 8

N

G

-

I

V

D

P

R

O

B

E

S

GLI1 / SE 12
GATA4 (8p23) / SE 8 probehybridized to patient material
showing a deletion of the
GATA4 (8p23) region (1R2G).

GLI1 (12q13) / SE 12
hybridized to patient material
showing GLI (12q13)
amplification (3R2G).

Image kindly provided by Dr.
Wenzel, Basel.

GLI1 (12q13) / SE 12

GATA4 (8p23) / SE 8
CODE

COLOR

FORMATSTATUS

KBI-40118

Green/Red

10 testIVD

KBI-45118

Green/Red

5 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-10104

Green/Red

10 test

IVD

MENU
MENU

HEMATOPATHOLOGYPOSTNATALBACKGROUNDBACKGROUND

Trisomy 12 is the most common numerical chromosomal aberration in patientswith B-cell chronic lymphocytic leukemia (B-CLL). Partial trisomy 12 of the longarm of chromosome 12 consistently includes a smaller region at 12q13-15 and has
been observed in CLL and several other tumors. A number of loci located close toeither MDM2 or CDK4 / SAS, including the genes GADD153, GLI1 (previously known
as GLI), RAP1B, A2MR, and IFNG, were found to be coamplified.

The deletion of GATA4 (8p23) is found in patients with congenital heart disease.
Besides the deletion, duplications are found of the region flanked by low copy
repeats 8p-OR-REPD (distal) and -REPP (proximal). These recurrent deletions areassociated with a spectrum of anomalies, including developmental delay andneuropsychiatric findings. GATA4 is expressed in adult heart, epithelium andgonads. During fetal development, GATA4 is expressed in yolk sac endoderm andcells involved in heart formation.

The GLI1 (12q13) specific FISH probe is optimized to detect copy numbers of the
GLI1 gene region at region 12q13. The chromosome 12 Satellite Enumeration FISH
probe (SE 12) D12Z3 is included to facilitate chromosome identification.

The GATA4 (8p23) / SE 8 FISH probe is optimized to detect deletions of the GATA4gene region at 8p23 in a dual-color assay on metaphase/interphase spreads, bloodsmears and bone marrow cells. The Chromosome 8 Satellite Enumeration (SE)FISH probe is included to facilitate chromosome identification.

REFERENCES
Merup et al, 1997, Eur J Haematol, 58; 174-180.
Dierlamm et al., 1997, Genes Chrom Cancer, 20; 155-166.

REFERENCES
Bhatia et al, 1999, Prenat Diagn., 19; 863-867.
Giorda et al, 2007, Hum. Mut., 28; 459-468.
Wat et al, 2009, Am. J. Med. Genet., Part A, 149A; 1661-1677.

D12Z3

D12S1266

12q13

270 kB
GLI1
RH75890

REPD

8p23

3Mb

12

SE8
RH122631

GATA4

470 kB

RH121772

REPP

8* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
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187

A

D

V

A

N

C

E

D

S

T

A

I

N

I

HIRA / SHANK3

N

G

-

I

V

D

P

R

O

B

E

S

IGF1R / 15q11
DiGeorge HIRA (22q11) /22q13 (SHANK3) probehybridized to a normal
metaphase (2R2G).

IGF1R (15q26) / 15q11
probe hybridized to patientmaterial showing a deletionof the IGF1R gene region at
15q26 (1R2G).

DiGeorge HIRA (22q11) / 22q13 (SHANK3)

IGF1R (15q26) / 15q11

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KBI-40103

Green/Red

10 testIVD

KBI-40116

Green/Red

10 testIVD

KBI-45103

Green/Red

5 testIVD

KBI-45116

Green/Red

5 test

IVD

MENU

MENU

POSTNATALPOSTNATALBACKGROUNDBACKGROUND

The DiGeorge HIRA (TUPLE) probe targets a putative transcriptional regulator(TUPLE1 or HIRA, HIR histone cell cycle regulation defective homolog A) which
also has been identified to lie within the commonly deleted region DiGeorge
syndrome. This probe is located distally to the “N25” probe.

Congenital diaphragmatic hernia (CDH) is a severe, life-threatening, congenital
anomaly characterized by variable defect in the diaphragm, pulmonary hypoplasia,
and postnatal pulmonary hypertension. Deletion of the IGF1R (insulin-like growth
factor 1 receptor) gene region at 15q25 is the most frequent anomaly found in
CDH. The type 1 IGF receptor at 15q26 is required for normal embryonic andpostnatal growth. Deletions, but also gain of an approximately 5 Mb region
including the IGF1R gene has been found to have a profound effect on prenatal andearly postnatal growth.

The DiGeorge HIRA region probe is optimized to detect copy numbers of the HIRA
gene region at 22q11.2. The SHANK3 probe at 22q13 is serving as internal control.
REFERENCES

The IGF1R (15q26) specific FISH probe is optimized to detect copy numbers of the
IGF1R gene region at region 15q26. The 15q11 (SNRPN / UBE3A) specific region
probe is included to facilitate chromosome identification.

Lorain at al, 1996, Genome Res, 6; 43-50.

D22S1660

REFERENCES

DGCR2

Faivre et al, 2002, Eur, J, Hum, Genet., 10; 699-706.
Okubo et al, 2003, J. Clin. Endocrinol. Metab, 88; 5981-5988.

"N25"

CLTCL1
D22S1646
22q11.2

D22S553
RH54346

22

HIRA

220 kB
SNRPN

D221668

890 kB

22q13
15q11.2
RH8457

UBE3A

ARSA

SHANK3

D15S10130 kB

SHGC 154952

RH38881
15q26

15

IGF1R

540 kB

SHGC-3827* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
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188

A

D

V

A

N

C

E

D

S

T

A

I

N

I

IGH Break

N

G

-

I

V

D

P

R

O

B

E

S

IGH Break (tissue)
IGH (14q32) Break probehybridized to patient material
showing a partial deletion of
14q32 (1RG1R).

Hybridization of IGH breakprobe to a tissue section
showing normal and aberrant
pattern (2RG)(1RG1R1G)

IGH (14q32) BreakIGH (14q32) Break (tissue)

CODE

COLOR

FORMATSTATUS

KBI-10601

Green/Red

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-10729

Green/Red

10 test

IVD

MENU

MENU

HEMATOPATHOLOGYHEMATOPATHOLOGYBACKGROUNDBACKGROUND

Multiple myeloma is characterized by complex rearrangements involving the IgHgene, particularly at the constant locus. The IgH rearrangement provides a usefulmarker of clonality in B-cell malignancies and amplification of this rearrangement
is the method of choice to monitor the residual tumor cells in multiple myeloma.

Chromosomal rearrangements involving the immunoglobulin heavy chain
gene (IGH) at 14q32 are observed in 50% of patients with B-cell non-Hodgkin’s
lymphoma (NHL) and many other types of Lymphomas. More than 50 translocation
partners with IGH have been described. In particular t(8;14) is associated with
Burkitt’s lymphoma, t(11;14) is associated with Mantle cell lymphoma, t(14;18) isobserved in a high proportion of follicular lymphomas and t(3;14) is associatedwith Diffuse Large B-Cell Lymphoma.

The IGH (14q32) break probe is optimized to detect translocations involving the
IGH gene region at 14q32 in a dual-color, split assay.
REFERENCES

The IGH (14q32) Break probe is optimized to detect translocations involving the
IGH gene region at 14q32 in a dual-color, split assay.

Taniwaki et al, 1994, Blood, 83; 2962-1969.
Gozetti et al, 2002, Cancer Research, 62; 5523-5527.

REFERENCES
Taniwaki et al, 1994, Blood, 83: 2962-1969.
Gozetti et al, 2002, Cancer Research, 62: 5523-5527.

D14S683E

660 kB
RH44825

IGH

D14S683E

SHGC-170017
14q32

14

660 kB

460 kB
RH44825

D14S1420

IGH
SHGC-170017
14q32

14

460 kB
D14S1420* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
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189

A

D

V

A

N

C

E

D

S

T

A

I

N

I

IRF4 / DUSP22 Break

N

G

-

I

V

D

P

R

O

B

E

JAK2 BreakIRF4 / DUSP22 (6p25) Break.

JAK2 (9p24) Break probehybridized to bone marrow
sample (2RG).

Image kindly provided
by Hopital Universitario
Marqués de Valdecilla,
Satander.

IRF4 / DUSP22 (6p25) BreakJAK2 (9p24) Break

CODE

COLOR

FORMATSTATUS

KBI-10613

Green/Red

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-10012

Green/Red

10 test

IVD

MENU

MENU

HEMATOPATHOLOGYHEMATOPATHOLOGYBACKGROUNDBACKGROUND

Rearrangements of the 6p25.3 locus define a subtype of CTCL. Genes
rearranged at the 6p25.3 locus are IRF4 (also known as MUM1) and the DUSP22.
Rearrangements of the 6p25.3 locus have also been described to occur in high andlow grade B-cell lymphomas, myeloma and chronic B-cell lymphoid leukemia.

Janus Kinase 2 (JAK2) is a tyrosine kinase involved in cytokine signaling.
Mutations and translocations involving the JAK2 gene region are observed inmyeloproliferative neoplasms. The common JAK2617V>F point mutation andtranslocations results in constitutive activation of JAK2. Translocations aredescribed with the following fusion partners: PCM1, BCR, ETV6 (TEL), SSBP2 and
3q21. Patients with the JAK2617V>F point mutation can also exhibit a numerical
gain of the gene.

The IRF4 / DUSP22 (6p25) Break FISH probe detects both rearrangements involving
IRF4 and DUSP22, but does not distinguish them from each other.
The IRF4 / DUSP22 (6p25) Break FISH probe is optimized to detect translocations
involving the IRF4 / DUSP22 gene region at the 6p25.3 locus in a dual-color assay
on metaphase/interphase spreads, blood smears, bone marrow cells and lymph
node biopsies.

The JAK2 (9p24) Break FISH probe is optimized to detect translocations involving
the JAK2 gene region at region 9p24 in a dual-color, split assay on metaphase/interphase spreads. The JAK2 (9p24) Break FISH probe can not be used to detect
point mutations, and it has not been optimized to detect gene amplifications.jfeld
V et al, 2007, Exp Hematol, 35; 1668-1676.

REFERENCES

Smith C et al, 2008, Hum Pathol, 39; 795-810.
Poitras J et al, 2008, Genes Chromosomes Cancer, 47; 884-889.

Bisig et al., Best Pract Res Clin Haematol, 2012, 25; 13-28.
Feldman et al., Blood, 2011, 117; 915-919.
Karai et al., Am J Surg Pathol, 2013 [Epub ahead of print].
Pham-Ledard et al., J Invest Dermatol, 2010, 130; 816-825.
Salaverria et al., Blood, 2011, 118; 139-147.
Wada et al., Mod Pathol, 2011, 24; 596-605.

9p24

SHGC-149694

550 kB
RH63147

JAK2

RH92501

525 kB
6p25

RH12503
RH40877

D9S1969

100 kB

DUSP22
IRF4
RH409319500 kB
D6S1600

6* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
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190

S

A

D

V

A

N

C

E

D

S

T

A

I

N

I

KMT2A / AFF1

N

G

-

I

V

D

P

R

O

B

E

KMT2A / MLLT1
KMT2A / AFF1 t(4;11) Fusion
probe. Standard t(4;11)
2 Fusion, 1 Red, 1 Green(2F1R1G).

KMT2A / MLLT1 t(11;19)
Fusion probe hybridized topatient material showingt(11;19) translocation(2RG1R1G).

Image kindly provided by
Dr. Christine Harrison,
Newcastle.

KMT2A / AFF1 t(4;11) Fusion

KMT2A / MLLT1 t(11;19) Fusion

CODE

COLOR

FORMATSTATUS

KBI-10404

Green/Red

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-10307

Green/Red

10 test

IVD

MENU

MENU

HEMATOPATHOLOGYHEMATOPATHOLOGYBACKGROUNDBACKGROUND

The t(4;11) KMT2A / AFF1 is the most frequently (approximately 66% according
to Meyer et al.) observed translocation involving the KMT2A gene resulting in
ALL. The KMT2A / AFF1 translocation results in the generation of fusion proteins
KMT2A / AFF1 and AFF1 / KMT2A; both seem to have leukemogenic properties.
Furthermore, MECOM (3q26) is one of the targets of the KMT2A oncoproteins,which increased expression correlates with unfavorable prognosis in Acute
Myeloid Leukemia.

One of the relatively frequently observed translocations (around 10 %) in AML and
ALL involves the genes KMT2A (previously known as MLL) and MLLT1 (aka ENL)
at 11q23 and 19p13. The KMT2A / MLLT1 translocation results in the generationof fusion protein that retains the MLL N-terminus, including both an A-T hookdomain and a region similar to mammalian DNA methyltransferase. There areseveral breakpoints within the MLLT1 gene described, without clear differencesin clinicohematologic features. The KMT2A / MLLT1 Fusion probe is optimized
to detect translocations involving the KMT2A and MLLT1 gene regions at 11q23
and 19p13 in a dual-color, fusion assay on metaphase/interphase spreads, bloodsmears and bone marrow cells in a dual-color, fusion assay.

The KMT2A / AFF1 t(4;11) Fusion FISH probe is optimized to detect translocations
involving the KMT2A (previously known as MLL) and AFF1 gene regions at 4q21-22
and 11q23 in a dual-color, fusion assay on metaphase/interphase spreads, bloodsmears and bone marrow cells.

REFERENCES
Mitterbauer-Hohdanner G et al, 2004, Eur J Clin Invest, 34; 12-24.
Meyer C et al, 2009, Leukemia, 23; 1490-1499.
Fu JF et al, 2007, Am J Clin Pathol, 127; 24-30.

REFERENCES
Harrison CJ et al, 2010, Br J Haem, 151; 132-142.
Arai S et al, 2011, Blood, 117; 6304-6314
Meyer C et al, 2009, Leukemia, 23; 1490-1499.

19p13.3

D11S3416

D4S2462

KMT2A
(MLL)

D11S3416

4q21-22

AFF1

KMT2A
(MLL)

950 kB
11q23

1030 kB

11q23

HUMUT841

MLLT1
(ENL)
1030 kB

19

RH80857

D11S2682

11

D11S2682

11
RH59505

4* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

191

1460 kB

S

A

D

V

A

N

C

E

D

S

T

A

I

N

I

KMT2A / MLLT3

N

G

-

I

V

D

P

R

O

B

E

S

KMT2A / MLLT4
KMT2A/MLLT3 t(9;11)
Fusion probe hybridized topatient material showingt(9;11) translocation(2RG1R1G).

KMT2A / MLLT4 t(6;11)
Fusion probe hybridized
to patient material
showing 47,XX,t(6;11)(q27;q23),+der(6)t(6;11)(q27;q23).

Image kindly provided by Dr.
Mohr, Dresden.

KMT2A / MLLT3 t(9;11) Fusion

KMT2A / MLLT4 t(6;11) Fusion

CODE

COLOR

FORMATSTATUS

KBI-10308

Green/Red

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-10309

Green/Red

10 test

IVD

MENU

MENU

HEMATOPATHOLOGYHEMATOPATHOLOGYBACKGROUNDBACKGROUND

Chromosomal rearrangements involving the mixed lineage leukemia (MLL) geneat 11q23 are frequently observed in adult and childhood acute leukemia and are,in general, associated with poor prognosis. However, children with Acute Myeloid
Leukemia (AML) carrying the t(9;11) KMT2A / MLLT3 (aka AF9) translocation havebeen described to be more sensitive to chemotherapy than patients with other
11q23 rearrangements.

One of the relatively frequently observed translocations in AML involves the genes
KMT2A and MLLT4 (previously known as AF6) at 11q23 and 6q27. The KMT2A/ MLLT4 translocation results in the generation of fusion protein that retains theKMT2A N-terminus, including both an A-T hook domain and a region similar to
mammalian DNA methyltransferase. The breakpoint region of the MLLT4 gene islocated within intron 1 and downstream of the initiation codon.

The KMT2A / MLLT3 Fusion FISH probe is optimized to detect translocations
involving the KMT2A (previously known as MLL) and MLLT3 gene regions at 11q23
and 9p21 in a dual-color fusion assay on metaphase/interphase spreads, bloodsmears and bone marrow cells.

The KMT2A / MLLT4 t(6;11) Fusion FISH probe is optimized to detect
translocations involving the KMT2A (previously known as MLL) and MLLT4 generegions at 11q23 and 6q27 in a dual-color, fusion assay on metaphase/interphasespreads, blood smears and bone marrow cells.

REFERENCESREFERENCES

Von Lindern et al, 1992, Mol. Cell. Biol.,12; 1687-1697.
Ageberg et al, 2008, Gen. Chrom. Canc., 47; 276-287.
Chi et al, 2008, Arch. Pathol. Lab. Med.,132; 1835-1837.

Mitterbauer-Hohdanner G et al, 2004, Eur J Clin Invest, 34; 12-24.
Meyer C et al, 2009, Leukemia, 23; 1490-1499.

SHGC-51155
9p21

MLLT3
(AF9)

D11S3416

KMT2A
(MLL)

RH93561

11q23

9

D11S3416

SHGC-77766

1080 kB

KMT2A
(MLL)

1030 kB

1480 kB
MLLT4
(AF6)

D11S2682

11

6q27

6

11q23

D11S2682

11

SHGC-144743* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

192

1030 kB

A

D

V

A

N

C

E

D

S

T

A

I

N

I

KMT2A / SE 11

N

G

-

I

V

D

P

R

O

B

E

S

KMT2A BreakKMT2A (11q23) / SE
11 hybridized to normalinterphases (2R2G).

Hybridization of KMT2A
probe to a metaphasespread showing normal
pattern (2F).

KMT2A (11q23) / SE 11

KMT2A (11q23) Break

CODE

COLOR

FORMATSTATUS

KBI-10711

Green/Red

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-10303

Green/Red

10 test

IVD

MENU

MENU

NEUROPATHOLOGYHEMATOPATHOLOGYBACKGROUNDBACKGROUND

Deletions of the long arm of chromosome 11 (11q) have been noted in primaryneuroblastomas. It is assumed that a tumor suppressor gene mapping within
11q23.3 is commonly inactivated during the malignant evolution of a large
subset of neuroblastomas, especially those with unamplified MYCN. The KMT2A(11q23) FISH probe is optimized to detect amplification or deletion involving
the KMT2A gene region at 11q23 in a dual-color assay. The Chromosome 11
Satellite Enumeration probe (SE 11) at D11Z1 is included to facilitate chromosome
identification.

The human chromosome band 11q23 is associated with a high number ofrecurrent chromosomal abnormalities including translocations, insertions, anddeletions. It is involved in over 20% of acute leukemias. The KMT2A (previously
known as MLL) gene, named for its involvement in myeloid (usually monoblastic)
and lymphoblastic leukemia, and less commonly in lymphoma, is located in the
11q23 breakpoint region. Leukemias involving the KMT2A gene usually have a poor
prognosis.
The KMT2A (11q23) Break FISH probe is optimized to detect translocations
involving the KMT2A gene region at 11q23 in a dual-color split assay.

REFERENCES
Guo et al, 1999, Oncogene, 18: 4948-4957.
Maris et al, 2001, Med Pediatr Oncol, 36: 24-27.

REFERENCES
Kobayashi et al, 1993, Blood, 81; 3027-3022
Martinez-Climent et al, 1995, Leukemia, 9; 1299-1304.

SE11
SHGC-85140

SHGC-85140

11q23

11

KMT2A
(MLL)

310 kB
RH92387

720 kB

KMT2A

D11S1930

SHGC-111513

265 kB

11q23

11

D11S1930* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

193

A

D

V

A

N

C

E

D

S

T

A

I

N

I

MAF/ IGH

N

G

-

I

V

D

P

R

O

B

E

S

MAFB /IGH
MAF / IGH t(14;16) Fusion
probe hybridized to patientmaterial showing a deletionof the MAF gene region at
16q23 (2R1G).

The MAFB / IGH t(14;20)
Fusion FISH probe hybridized
to patient material showing
a complex pattern with at(14;20) translocation.

Image kindly provided by
Erasmus Medical Center,
Rotterdam.

MAF / IGH t(14;16) Fusion

MAFB / IGH t(14;20) Fusion

CODE

COLOR

FORMATSTATUS

KBI-10610

Green/Red

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-10510

Green/Red

10 test

IVD

MENU

MENU

HEMATOPATHOLOGYHEMATOPATHOLOGYBACKGROUNDBACKGROUND

Abnormalities of 16q are important recurrent events in multiple myeloma (MM).
The t(14;16)(q32;q23) is a karyotypically silent translocation that is associatedwith the ectopic expression and dysregulation of MAF mRNA. Translocations thatbracket the MAF locus (dispersed over 500 kb) are estimated to be present in up to
25% of plasma cell myelomas.

The immunoglobulin heavy chain (IGH) gene at 14q32 is an important causeof genetic deregulation in MM. Among the known fusion partners for the IGH(previously known as IGH@) gene, reciprocal translocation with the MAFB gene at
20q12 is relatively rare in MM (~2% occurrence). However, the MAFB / IGH t(14;20)translocation is associated with poor prognosis in multiple myeloma patients.

The MAF / IGH t(14;16) specific FISH probe is optimized to detect the reciprocaltranslocation t(14;16) in a dual-color, dual-fusion assay on metaphase/interphasespreads, blood smears and bone marrow cells.

The MAFB / IGH t(14;20) Fusion FISH probe is optimized to detect the reciprocaltranslocation t(14;20) in a dual-color, dual-fusion assay on metaphase/interphasespreads and bone marrow cells.

REFERENCESREFERENCES

Chesi et at, 1998, Blood 91; 4457-4463.
Sawyer et al, 1998, Blood 92; 4269-4278.

Boersma-Vreugdenhil GR et al, 2004, Br J Haematol, 126; 355-363.
Bergsagel PL et al, 2005, JCO, 23; 6333-6338.

SHGC-105199
D14S683E

RH123327

D14S683E

530 kB

515 kB

SHGC-78905

WWOX
IGH

MAF

1420 kB
16q23

14q32

14

RH6679016

Gap: 2.2 MB

IGH

RH69965
SHGC-79420

500 kB

1420 kB

20

14q32

14

20q12

MAFB
528 kB
RH10684

RH66790* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
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194

A

D

V

A

N

C

E

D

S

T

A

I

N

I

MALT1 Break

N

G

-

I

V

D

P

R

O

B

E

S

MALT1 Break (tissue)
MALT1 (18q21) Break probehybridized to patient material
showing a translocation at
18q21 (1RG1RG).

MALT1 (18q21) Break tissue
probe hybridized to paraffin
embedded material (2RG).

MALT1 (18q21) BreakMALT1 (18q21) Break (tissue)

CODE

COLOR

FORMATSTATUS

KBI-10608

Green/Red

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-10731

Green/Red

10 test

IVD

MENU

MENU

HEMATOPATHOLOGYHEMATOPATHOLOGYBACKGROUNDBACKGROUND

Low grade malignant lymphomas arising from mucosa associated lymphoidtissue (MALT) represent a distinct clinicopathological entity. The three majortranslocations seen in MALT lymphomas are t(11;18)(q21;q21) / API2-MALT1,
t(14;18)(q32;q21) / IGH-MALT1 and t(1;14)(p22;q32) / IGH-BCL10. A break or split
probe for MALT1 (18q21) is best used to analyze translocation of the MALT1 geneon formalin fixed paraffin embedded tissue for routine clinical diagnosis.

Low grade malignant lymphomas arising from mucosa associated lymphoidtissue (MALT) represent a distinct clinicopathological entity. The three majortranslocations seen in MALT lymphomas are t(11;18)(q21;q21) / API2-MALT1,
t(14;18)(q32;q21) / IGH-MALT1 and t(1;14)(p22;q32) / IGH-BCL10. A break or split
probe for MALT1 (18q21) is best used to analyze translocation of the MALT1 geneon formalin fixed paraffin embedded tissue for routine clinical diagnosis.

Kreatech has optimized this FISH probe for the specific use on cell material (KBI10608), or for the use on tissue (KBI-10731).

The MALT1 (18q21) Break probe is optimized to detect translocations involving the
MALT1 gene region at 18q21 in a dual-color, split assay.

REFERENCES

Kreatech has developed this probe for the specific use on cell material (KBI10608), or for the use on tissue (KBI-10731).

Morgan et al, 1999, Cancer Res, 59; 6205-6213.
Dierlamm et al, 2000, Blood, 96; 2215-2218.

WI-5827
D18S881

REFERENCES
Morgan et al, 1999, Cancer Res, 59; 6205-6213.
Dierlamm et al, 2000, Blood, 96; 2215-2218.

345 kB

MALT1
18q21

RH93602
WI-5827680 kB

18

D18S881

RH103885

345 kB

MALT1
18q21

RH93602680 kB

18

RH103885* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
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195

A

D

V

A

N

C

E

D

S

T

A

I

N

I

MDM2 / SE 12

N

G

-

I

V

D

P

R

O

B

E

S

MDM4 / SE 1
MDM2 (12q15) / SE
12 Amplification probehybridized to patient material
showing amplification of the
MDM2 gene region at 12q15.

MDM4 (1q32) / SE 1 probehybridized to paraffin
embedded tissue (2R2G).

MDM2 (12q15) / SE 12

MDM4 (1q32) / SE 1

CODE

COLOR

FORMATSTATUS

KBI-10717

Green/Red

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-10736

Green/Red

10 test

IVD

MENU

MENU

SOFT TISSUE PATHOLOGYNEUROPATHOLOGYBACKGROUNDBACKGROUND

Well-differentiated liposarcoma/atypical lipomatous tumor and dedifferentiatedliposarcoma are among the most common malignant soft tissue tumors presented
in older adults. These tumors can be difficult to distinguish from benign lipomatous
neoplasms and other high-grade sarcomas.

MDM4 (MDM4 p53 binding protein homolog (mouse), also known as MDMX,
murine double minute gene) is a relative of MDM2 that was identified on the basisof its ability to physically interact with TP53. MDM4, like MDM2, acts as a key
negative supressor of TP53 by interfering with its transcriptional activity. MDM4
amplification and/or overexpression occurs in several diverse tumors. Studies
showed an increased MDM4 copy number in 65% of human retinoblastomas
compared to other tumors, qualifying MDM4 as a specific chemotherapeutic target
for treatment of this tumor.

Amplification of the MDM2 gene has been identified in lipomatous neoplasms.
The use of fluorescence in situ hybridization in identifying MDM2 amplification
has made the MDM2 amplification probe a valuable diagnostic tool in welldifferentiated liposarcomas/atypical lipomatous tumors. The MDM2 (12q15) FISH
probe is optimized to detect copy numbers of the MDM2 gene region at region
12q15.

The MDM4 (1q32) FISH probe is designed as a dual-color assay to detect
amplification at 1q32. The chromosome 1 Satellite Enumeration (SE 1) probe at
1qh is included to facilitate chromosome identification.

The chromosome 12 satellite enumeration probe (SE 12) at D12Z3 is included tofacilitate chromosome identification.

REFERENCES
Riemenschneider et al, 1999, Cancer Res. 59 ; 6091-6096.
Danovi et al, 2004, Mol.Cell.Biol. 24; 5835-5843.

REFERENCES
Uchida et al, 2010, Cancer Genet Cytogenet 203; 324-327.
Lucas et al, 2010, Am J Surg Pathol 34: 844-851.
Weaver et al, 2008, Mod Pathol 21: 943-949.
Mitchell et al, 1995, Chrom. Res., 3; 261-262.
Reifenberger et al, 1996, Cancer Res., 15; 5141-5145.

D12Z3

RH28583

1qh
12q15

MDM2

530 kBSTSG27747

MDM4
D12S1497

450 kB

1q32

12

SHGC-148562

1* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

196

A

D

V

A

N

C

E

D

S

T

A

I

N

I

MECOM Break

N

G

-

I

V

D

P

R

O

B

E

MECOM Break Triple-Color
MECOM t(3;3);inv(3) (3q26)
Break probe hybridized topatient material showing arearrangement involving the
MECOM gene region at 3q26
(1RG1R1G).

MECOM t(3;3);inv(3) (3q26)
Break probe hybridized topatient material showing arearrangement involving the
MECOM gene region at 3q26
(1RG1R1G).

Image kindly provided by Dr.
Reed, London.

Image kindly provided by Dr.
Reed, London.

MECOM t(3;3); inv(3) (3q26) BreakMECOM t(3;3); inv(3) (3q26) Break, Triple-Color

CODE

COLOR

FORMATSTATUS

KBI-10204

Green/Red

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-10205

Green/Red/Blue

10 test

IVD

MENU

MENU

HEMATOPATHOLOGYHEMATOPATHOLOGYBACKGROUNDBACKGROUND

The inv(3)(q21;q26) is a recurrent cytogenetic aberration of myeloid malignancy
associated with fusion of MECOM (EVI) and RPN1. Genomic breakpoints in 3q26
are usually located proximal to the MECOM locus, spanning a region of several
hundred kilobases. Other recurrent and sporadic rearrangements of 3q26 also
cause transcriptional activation of MECOM including the translocations t(3;3)(q21;q26) and t(3;21)(q26;q22). Breakpoints in the latter rearrangements spana wider genomic region of over 1 megabase encompassing sequences distal to
MECOM and neighboring gene MDS1.

The MECOM t(3;3); inv(3)(3q26) Break Triple-Color FISH probe is optimized todetect the inversion of chromosome 3 involving the MECOM (previously known
as EVI) gene region at 3q26 in a dual-color, split assay on metaphase/interphasespreads, blood smears and bone marrow cells. By using a third color breakpoint
variations can also be easily observed.
REFERENCES
De Braekeleer et al, 2011, Anticancer Res, 31; 3441-3448;
Levy E. et al, 1994, Blood, 83; 1348-1354.
Cui W. et al, 2011, Am J Clin Pathol, 136; 282-288.
Wieser R et al, 2003, Haematologica, 88; 25-30.
De Melo V. et al, 2007, Leukemia aop, 13 Sep, 1-4.
Shearer B. et al, 2010, Am J Hematol, 85:569-574.

The MECOM t(3;3) inv(3) Break, dual-color FISH probe is optimized to detect
the inversion of chromosome 3 involving the MECOM gene region at 3q26 in adual-color, split assay on metaphase/interphase spreads, blood smears and bonemarrow cells.
REFERENCES

RH103072

De Braekeleer et al, 2011, Anticancer Res, 31; 3441-3448.
Shearer B. et al, 2010, Am J Hematol, 85:569-574.
Cui W. et al, 2011, Am J Clin Pathol, 136; 282-288.
De Melo V. et al, 2007, Leukemia aop, 13 Sep, 1-4.
Levy E. et al, 1994, Blood, 83; 1348-1354.
Wieser R et al, 2003, Haematologica, 88; 25-30.

420 kB
RH67219

MECOM(EVI1)

GAP: 590 kB

RH17919TERC

3q26.2

D3S12433

470 kB590 kB

RH10606
RH111834

RH123089

550 kB

SHGC-85783

MECOM(EVI1)

GAP: 370 kB

RH17919

3q26.2

3TERCS590 kB

RH10606* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

197

A

D

V

A

N

C

E

D

S

T

A

I

N

I

MECOM/RUNX1

N

G

-

I

V

D

P

R

O

B

E

S

MET / SE 7
MECOM / RUNX1 Fusion
probe hybridized to patientmaterial showing t(3;21)(2F1R1G).

Hybridization of MET
Amplification probe to atissue section showing MET
amplification.

Image kindly provided by Dr.
Mohr, Dresden.

MECOM / RUNX1 t(3;21) Fusion

MET (7q31) / SE 7

CODE

COLOR

FORMATSTATUS

KBI-10310

Green/Red

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-10719

Green/Red

10 test

IVD

MENU

MENU

HEMATOPATHOLOGYLUNG PATHOLOGYBACKGROUNDBACKGROUND

The MECOM (EVI1, 3q26) / RUNX1 (AML1, 21q22) translocation, t(3;21), is
consistently found in blastic crisis of chronic myelocytic leukemia (CML) andmyelodysplatic syndromederived leukemias. The translocation produces RUNX1/ MECOM chimeric transcription factor and is thought to play important rolesin acute leukemic transformation of hemopoietic stem cells. The MECOM /RUNX1 t(3;21) Fusion specific FISH probe is optimized to detect the reciprocaltranslocation t(3;21) in a dual-color, dual-fusion assay on metaphase/interphasespreads, blood smears and bone marrow cells.

The MET proto-oncogene is a receptor-like tyrosine kinase that drives aphysiological cellular program important for development, cell movement, cell
repair and cellular growth. Aberrant execution of this program has been associatedto neoplastic transformation, invasion and metastasis. Activation of MET has beenreported in a significant percentage of human cancers including non-small cell lungcancer (NSCLC) and is amplified during the transition between primary tumors andmetastasis.
The MET (7q31) FISH probe is optimized to detect copy numbers of the MET generegion at region 7q31. The Chromosome 7 Satellite enumeration probe (SE 7) at
D7Z1 is included to facilitate chromosome identification.

REFERENCES
Mitani et al., EMBO, 1994, Vol 13, 504-510.
Tanaka et al., Mol Cell Biol, 1995, 2383-2392.

REFERENCES
Go et al, 2010, J Thorac Oncol 5: 305-313.
Hara et al, 1998, Lab Invest 78; 1143-1153.
Tsugawa et al, 1998, Oncology 55; 475-481.

D21S325

D3S1243
21q22

470 kB21

SHGC-85783

MECOM(EVI1)RUNX1(AML1)

1380 kB

SHGC-9898

GAP: 370 kB

D7Z1

RH17919
D7S3086
3q26.23TERC

590 kB
7q31

RH10606

MET

450 kB

SHGC-79904

7* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

198

A

D

V

A

N

C

E

D

S

T

A

I

N

I

Mm-BCR / ABL1

N

G

-

I

V

D

P

R

O

B

E

S

MYC (8q24) BreakMm-BCR / ABL1 probehybridized to patient material
showing t(9;22) with M-BCR(1F1r1R1G).

MYC (8q24) Break probehybridized to patient material
showing a 8q24 proximal
break (1GBR1G1BR).

Image kindly provided by
Prof. Siebert, Kiel.

Mm-BCR / ABL1 t(9;22) Dual-Color, Single-Fusion, Extra Signal
CODE

COLOR

FORMATSTATUS

KBI-10013

Green/Red

10 testIVD

MYC (8q24), Triple-Color, Break
CODE

COLOR

FORMATSTATUS

KBI-10611

Green/Red/Blue

10 test

IVD

MENU

MENU

HEMATOPATHOLOGYHEMATOPATHOLOGYBACKGROUNDBACKGROUND

Breakpoints in the BCR gene region can occur in different regions, predominantely
in a major breakpoint cluster region (M-BCR) but can also occur in a minor
breakpoint cluster region (m-BCR) or micro breakpoint cluster region (µ-BCR).
Further research has indicated that CML patients with different BCR-ABL1
transcripts respond differently to treatment with Gleevec.

Rearrangements of the protooncogene MYC (C-MYC) have been consistently foundin Burkitt’s lymphoma tumor cells. In cases with the common t(8;14) chromosomaltranslocation, the MYC gene is translocated to chromosome 14 and rearranged
with the immunoglobulin heavychain genes; the breakpoint occurs 5’ to the MYC
gene and may disrupt the gene itself. In Burkitt’s lymphoma showing the variantt(2;8) or t(8;22) translocations, the genes coding for the k and l immunoglobulin
light chain are translocated to chromosome 8. The rearrangement takes place 3’ tothe MYC gene.

The Mm-BCR / ABL1 t(9;22), Dual-Color (DC), Single-Fusion (SF), Extra -Signal(ES) FISH probe is designed to differentiate between a M-BCR and m-BCR generearrangement by giving different signal patterns.

The MYC (8q24) Break probe is optimized to detect rearrangements involving the
8q24 locus in a triple-color, split assay on metaphase/interphase spreads, bloodsmears and bone marrow cells.

REFERENCES
Dewald et al., 1998, Blood, 91; 3357-3365.
Huntly et al., 2003, Blood, 102; 1160-1168.
Sharma et al., 2010, Ann Hematol, 89; 241-7.
Tkachuk et al., 1990, Science, 250; 559-56.
Kolomietz et al., 2001. Blood, 97; 3581-3588.

REFERENCES
Fabris et al, 2003, Genes Chromosomes Cancer, 37;261-269.
Hummel et al, 2006, N Engl J Med, 354; 2419-30.
1

D8S1813

SHGC-147754

22q11.2

ABL1

9

RH77966

480 kBBCR
HUMUT7039

NUP214
D9S1991

880 kB

IGLL51050 kB

22
9q34

m-BCR

D22S940

ASS1

IGLL1

D8S1128
2
3
4
6

MYC
5

7
8
9 10
11 12
13 14
15
16
17
19
21

740 kB

SHGC-172475
D8S1017
b1
b2
b3
b4
b5

M-BCR

870 kB

8q24.2

HUMUT7039

8

18
20

RH75025

22

23* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

199

A

D

V

A

N

C

E

D

S

T

A

I

N

I

MYC (8q24) Break (tissue)

N

G

-

I

V

D

P

R

O

B

E

MYC / SE 8
Hybridization of MYC TC
break probe to a tissue
section showing abarrant
pattern (1GBR1G1BR).

MYC (8q24) / SE 8 hybridized
to a metaphase spreadshowing a normal pattern.

MYC (8q24) Triple-Color, Break (tissue)

MYC (8q24) / SE 8

CODE

COLOR

FORMATSTATUS

KBI-10749

Green/Red/Blue

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-10106

Green/Red

10 test

IVD

MENU

MENU

HEMATOPATHOLOGYHEMATOPATHOLOGYBACKGROUNDBACKGROUND

Rearrangements of the proto oncogene MYC c-myc) have been consistently foundin Burkitt’s lymphoma tumor cells . In cases with the common t(8;14) chromosomaltranslocation, the MYC gene is translocated to chromosome 14 and rearranged
with the immunoglobulin heavy chain genes; the breakpoint occurs 5’ to the MYC
gene and may disrupt the gene itself. In Burkitt’s lymphoma showing the variantt(2;8) or t(8;22) translocations, the genes coding for the k and l immunoglobulin
light chain are translocated to v-myc avian myelocytomatosis viral oncogene
homolog (MYC or c-myc) chromosome 8.

The MYC (previously known as C-MYC) gene produces an oncogenic transcription
factor that affects diverse cellular processes involved in cell growth, cellproliferation, apoptosis and cellular metabolism. The MYC oncogene has beenshown to be amplified in many types of human cancer such as bladder, breastand cervical. Amplification at 8q24 including MYC is also observed in 5% of CLL
patients. MYC is also the prototype for oncogene activation by chromosomaltranslocation.
The MYC (8q24) specific FISH probe is optimized to detect copy numbers of the
MYC gene region at 8q24. The chromosome 8 Satellite Enumeration FISH probe(SE 8) at D8Z1 is included to facilitate chromosome identification.

The MYC (8q24) Break probe is optimized to detect rearrangements involving the
8q24 locus in a triple-color, split assay on formalin fixed paraffin embedded tissue.
REFERENCESREFERENCES

Fabris et al, 2003, Genes Chromosomes Cancer, 37;261-269.
Hummel et al, 2006, N Engl J Med, 354; 2419-30.

Greil et al, 1991, Blood, 78; 180-191.

D8S1813D8Z1

880 kB

SHGC-140056

MYC

RH77966
D8S1128

MYC

SHGC-144185

D8S10178

215 kB

740 kB

SHGC-172475

8q24.2870 kB

8q24.2S

8

RH75025* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

200

A

D

V

A

N

C

E

D

S

T

A

I

N

I

MYC / IGH t(8;14) Fusion

N

G

-

I

V

D

P

R

O

B

E

MYCN / AFF3
Hybridization of MYC/IGH
fusion probe to a metaphasespread showing normal
pattern (2R2G).

MYCN (2p24) / AFF3 (2q11)
hybridized to a cell line
showing amplification of
MYCN on chromosome 13
and 15.

Image kindly provided by
Pasteur Workshop 2008,
Paris.

MYC / IGH t(8;14) Fusion

MYCN (2p24) / AFF3 (2q11)

CODE

COLOR

FORMATSTATUS

KBI-10603

Green/Red

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-10706

Green/Red

10 test

IVD

MENU

MENU

HEMATOPATHOLOGYNEUROPATHOLOGYBACKGROUNDBACKGROUND

The translocation t(8;14)(q24;q32) is the characteristic chromosomal aberrationof Burkitt’s-type of lymphomas. This translocation fuses the MYC gene at 8q24
next to the IGH locus at 14q32, resulting in overexpression of the transcription
factor MYC. Detection of the t(8;14) is aimed to help in the diagnostic process ofpatients with high-grade B-cell lymphomas because treatment strategies differ
between Burkitt and other high-grade lymphomas. The MYC / IGH t(8;14)(q24;q32)
specific FISH probe is optimized to detect the reciprocal translocation t(8;14) in adual-color, dual-fusion assay.

Amplification of the human protooncogene, v-myc avian myelocytomatosis viraloncogene neuroblastoma derived homolog (MYCN) is frequently seen either
in extrachromosomal double minutes or in homogeneously staining regions of
aggressively growing neuroblastomas. MYCN amplification has been defined by
the INRG as > 4-fold MYCN signals compared to 2q reference probe signals.
The MYCN (2p24) FISH probe is optimized to detect copy numbers of the MYCN
gene region at 2p24. The AFF3 gene region probe at 2q11 is included to facilitate
chromosome identification.

REFERENCESREFERENCES

Veronese et al, 1995, Blood, 85;2132-2138.
Siebert et al, 1998, Blood, 91; 984-990.

Shapiro et al, 1993, Am J Pathol, 142: 1339-1346.
Corvi et al, 1994, PNAS, 91: 5523-5527.

RH40515

D14S683E

2p24

RH67659

MYCN

MYC

IGH

1270 kB

670 kB

1420 kB
RH30315

14q32
8q24.2814RH66790

2q11.2

SHGC-84336

SHGC-172475

AFF3

375 kB

RH670982* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

201

S

A

D

V

A

N

C

E

D

S

T

A

I

N

I

MYEOV / IGH

N

G

-

I

V

D

P

R

O

B

E

“N25” / SHANK3MYEOV / IGH t(11;14) Fusion
probe hybridized to MM
patient material showingt(11;14) translocation(2RG1R1G).

DiGeorge “N25” (22q11)/ 22q13 (SHANK3) probehybridized to a normal
metaphase (2R2G).

Image kindly provided by
Prof. Jauch, Heidelberg.

MYEOV / IGH t(11;14) Fusion

DiGeorge “N25” (22q11) / 22q13 (SHANK3)

CODE

COLOR

FORMATSTATUS

KBI-10605

Green/Red

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-40102

Green/Red

10 testIVD

KBI-45102

Green/Red

5 testIVD

MENU
HEMATOPATHOLOGYMENUPOSTNATALBACKGROUNDBACKGROUND

The most common chromosomal translocation in multiple myeloma (MM)is t(11;14), resulting in up-regulation of cyclin D1. In MM the breakpoints arescattered within a 360-kb region between CCND1 and MYEOV. This breakpoint ismore proximal than the t(11;14) breakpoints observed in mantle cell lymphoma orother leukemias. Patients with MM who have t(11;14)(q13;q32) seem to have an
aggressive clinical course.

The DiGeorge “N25” FISH probe was the first commercial microdeletion probe forchromosome 22q and detects the locus D22S75. This marker is located between
DGCR2 and CLTCL1 (Clathrin). Both genes have been extensively investigated andtheir role in DiGeorge syndrome is well established.
The DiGeorge “N25” region probe covers the marker “N25” (D22S75) and adjacentregion of CLTCL1 (Clathrin gene region) and DGCR2 (DiGeorge critical region gene2). The SHANK3 FISH probe at 22q13 is serving as internal control.

The MYEOV / IGH t(11;14)(q13;q32) Fusion specific FISH probe is optimized todetect the reciprocal translocation t(11;14) in a dual-color, dual-fusion assay.
REFERENCESREFERENCES

Janssen et al., 2000, Blood, 95; 2691-2698.
Fonseca et al, 2002, Blood, 99; 3735-3741.

Sirotkin et al, 1996, Hum. Mol. Genet., 5; 617-624.
Holmes et al, 1997, Hum. Mol. Genet., 6; 357-367.
Wilson, et al, 2003, J. Med. Genet., 40; 575-584.
Luciani, et al, 2003, J. Med. Genet., 40; 690-696.

D11S1138
D14S683E

510 kB
RH69373

MYEOV

D22S1660

IGH

11q13

1420 kB

DGCR2

CCND1
RH67810

FGF4
FGF3

11

"N25"

14q32

550 kB

14

RH66790315 kB

CLTCL1
D22S1646

RH48109

22q11.2

22

D22S553

HIRA
22q13
RH8457

ARSA
130 kBSHANK3
RH38881* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
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202

S

A

D

V

A

N

C

E

D

S

T

A

I

N

I

NF1 / MPO

N

G

-

I

V

D

P

R

O

B

E

S

NSD1 / TERTNF1 (17q11) / MPO (17q22)
probe hybridized to patientmaterial showing a deletionof NF1 gene region at 17q11(1R2G).

NSD1 (5q35) / TERT (5p15)
probe hybridized to a normal
metaphase (2R2G).

NF1 (17q11) / MPO (17q22)

NSD1 (5q35) / TERT (5p15)

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KBI-40114

Green/Red

10 testIVD

KBI-40113

Green/Red

10 testIVD

KBI-45114

Green/Red

5 testIVD

KBI-45113

Green/Red

5 test

IVD

MENU

MENU

POSTNATALPOSTNATALBACKGROUNDBACKGROUND

NF1, or Von Recklinghausen disease, is one of the most common hereditaryneurocutaneous disorders in humans and one of the most common single gene
syndromes. Clinically, NF1 is characterized by café-au-lait spots, freckling, skinneurofibroma, plexiform neurofibroma, bone defects, Lisch nodules and tumorsof the central nervous system. The responsible gene, NF1 (neurofibromin), wasidentified on chromosome 17q11. Whole NF1 gene deletions occur in 4%-5% of
individuals with NF1 and can be detected by FISH analysis.

NSD1 microdeletions (chromosome 5q35) are the major cause of Sotos syndrome,and occur in some cases of Weaver syndrome. Sotos is a childhood overgrowth
characterized by distinctive craniofacial features, advanced bone age, and mental
retardation. Weaver syndrome is characterized by the same criteria but has its
own specific facial characteristics. Sotos syndrome is inherited in an autosomal
dominant manner. While 50% of Sotos patients in Asia are showing a chromosomal
microdeletion, only 9% deletion cases are observed in the affected European
population.

The NF1 (17q11) region probe is optimized to detect copy numbers of the NF1gene region at 17q11.2. The MPO region specific FISH probe at 17q22 is included
as control probe.

The NSD1 (5q35) region probe is optimized to detect copy numbers of the NSD1
gene region at 5q35.2. The TERT region specific FISH probe at 5p15 is included ascontrol probe.

REFERENCESREFERENCES

Riva P et al, 2000, Am. J. Hum. Genet., 66; 100-109.
Dorschner et al, 2000, Hum. Mol. Genet., 9; 35-46.

Douglas et al, 2003, Am. J. Hum. Genet. 72; 132-143.
Rio et al, 2003, J. Med. Genet., 40; 436-440.

D17S1307

NF1

5p15.3
SHGC-154319

420 kBTERT390 kB

RH25868
17q11

D5S2269E
SHGC-16044

17q22

17

MPO

D5S2703

500 kB

NSD1

SHGC-144222
5q35

5330 kB

RH10047* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
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203

A

D

V

A

N

C

E

D

S

T

A

I

N

I

NUP98 Break

N

G

-

I

V

D

P

R

O

B

E

S

PAFAH1B1 / 17p11
NUP98 (11p15) Break
Probe hybridized to AML
patient sample showing arearrangement of 11p15
involving the NUP98 gene
(1F1R1G).

Miller-Dieker PAFAH1B1(17p13)/ Smith-Magenis
RAI1 (17p11) probehybridized to a normal
metaphase (2RG).

Image kindly provided by
Prof. Manuel R. Teixeira,Porto.

NUP98 (11p15) BreakMiller-Dieker PAFAH1B1 (17p13) / Smith-Magenis RAI1 (17p11)

CODE

COLOR

FORMATSTATUS

KBI-10311

Green/Red

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-40101

Green/Red

10 testIVD

KBI-45101

Green/Red

5 testIVD

MENU
HEMATOPATHOLOGYMENUPOSTNATALBACKGROUNDBACKGROUND

Nucleoporin 98kDa gene (NUP98) rearrangements have been identified in a wide
range of hematologic malignancies, including acute myeloid leukemia (AML), acutelymphoblastic leukemia (ALL), chronic myeloid leukemia in blast crisis (CML-bc),
myelodysplastic syndrome (MDS) and bilineage/biphenotypic leukemia. The
NUP98 gene is highly promiscuous with regard to its recombination spectrum, as
at least 28 different partner genes have been identified for NUP98 rearrangements,
all forming in-frame fusion genes. Patients with NUP98 gene rearrangements havean aggressive clinical course and the outcome of treatment is disappointing.

The Miller-Dieker lissencephaly syndrome appears to be caused by deletion ofseveral genes on 17p including the PAFAH1B1 (previously known as LIS1) gene.
About 15% of patients with isolated lissencephaly and more than 90% of patientswith Miller-Dieker syndrome have microdeletions in a critical 350-kb region at
17p13.3. Smith-Magenis is caused by a deletion of 17p11.2. The RAI1 (previously
known as SMCR, KIAA1820 or SMS) gene region has been identified to be deleted
in more than 90% of Smith-Magenis syndrome patients.

The NUP98 (11p15) Break FISH Probe is optimized to detect translocations
involving the NUP98 gene region at 11p15 in a dual-color assay on metaphase/interphase spreads, blood smears and bone marrow cells.

The Miller-Dieker PAFAH1B1 region probe is optimized to detect copy numbers of
the PAFAH1B1 region at 17p13. The Smith-Magenis RAI1 region probe is optimized
to detect copy numbers of the RAI1 gene region at 17p11.

REFERENCESREFERENCES

Gough et al, 2011, Blood, 118; 62 47-6257.
Nebral et al, 2005, Haematologica, 90; 74 6-752.
Romana et al, 2006, Leukemia, 20; 696-70 6.

Kuwano et al, 1991, Am. J. Hum. Genet., 49; 707-714.
Cardoso et al, 2003, Am. J. Hum. Genet., 72; 918-930.
Smith et al, 1986, Am. J. Med. Genet., 24; 393-414.
Greenberg et al, 1991, Am. J. Med. Genet., 49; 1207-1218.
Vlangos et al, 2005, Am. J. Med. Genet., 132; 278-282.

SHGC-84145
11p15

530 kB
RH75370

NUP98

GAP 455 kB
SHGC-5886

D11S452517p13

410 kB

PAFAH1B1

350 kB

SHGC-79113
D17S156611
17p11.2

17

UT159

RAI1
240 kB
RH68538* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
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204

A

D

V

A

N

C

E

D

S

T

A

I

N

I

PDGFRB Break

N

G

-

I

V

D

P

R

O

B

E

S

PML / RARAPDGFRB (5q32) Break probehybridized to a normal
metaphase (2RG).

PML / RARA t(15;17) Fusion
probe hybridized to a normal
metaphase (2R2G).

PDGFRB (5q32) BreakPML / RARA t(15;17) Fusion

CODE

COLOR

FORMATSTATUS

KBI-10004

Green/Red

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-10302

Green/Red

10 testIVD

KBI-12302

Green/Red

20 testIVD

MENU
HEMATOPATHOLOGYMENUHEMATOPATHOLOGYBACKGROUNDBACKGROUNDPDGFRB activation has been observed in patients with chronic myelomonocytic
leukemia/atypical chronic myeloid leukemia and has been associated with over
50 translocation partners, the best known is the ETV6 gene on 12p13, causing at(5;12) translocation. Cytogenetic responses are achieved with imatinib in patientswith PDGFRB fusion positive, BCR / ABL1 negative CMPDs.

REFERENCES

A structural rearrangement involving chromosomes 15 and 17 in acutepromyelocytic leukemia (APL) was first recognized in 1977. The critical junction is
located on the der(15) chromosome and consists of the 5’ portion of PML fused
to virtually all of the RARA gene. The PML / RARA fusion protein interacts with acomplex of molecules known as nuclear co-repressors and histone deacetylase.
This complex binds to the fusion protein and blocks the transcription of target
genes. Other less common variant translocations fuse the RARA gene on 17q21 to
the PLZF, NPM, NUMA, and STAT5b genes, respectively.

Wlodarska et al, 1997, Blood, 89; 1716-1722.
Wilkinson et al, 2003, Blood, 102; 4287-419.

The PML / RARA t(15;17) Fusion specific FISH probe is optimized to detect thereciprocal translocation t(15;17) (q24;q21) in a dual-color, dual-fusion assay.

The PDGFRB (5q32) Break FISH probe is optimized to detect translocations
involving the PDGFRB region at 5q32 in a dual-color, split assay.

REFERENCES
Schad et al, 1994, Mayo Clin Proc, 69; 1047-1053.
Brockman et al, 2003, Cancer Genet Cytogenet, 145; 144-151.

D5S1907

340 kB
RH58356
SHGC-149501

PDGFRB

SHGC-156300

RH70663PML

410 kB

715 kB

17q21

RARA

5q32
D5S2014

15q24

5

15

SHGC-148679

17

RH69878* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
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205

450 kB

A

D

V

A

N

C

E

D

S

T

A

I

N

I

PPARG Break

N

G

-

I

V

D

P

R

O

B

E

S

PTEN / SE 10
PPARG (3p25) Break probehybridized to patient material
showing a translocation at
3p25 (1RG1R1G).

PTEN (10q23) / SE 10 probehybridized to prostate cancermaterial showing deletion of
PTEN gene region at 10q23(1R2G).

Image kindly provided by Dr.
Valent, Paris.

Image kindly provided by
Portuguese Cancer Inst.,
Porto.

PPARG (3p25) BreakPTEN (10q23) / SE 10

CODE

COLOR

FORMATSTATUS

KBI-10707

Green/Red

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-10718

Green/Red

10 test

IVD

MENU

MENU

HEAD, NECK AND ENDOCRINE PATHOLOGYUROPATHOLOGYBACKGROUNDBACKGROUND

Follicular thyroid carcinoma is associated with the chromosomal translocationt(2;3)(q13;p25), fusing PAX8 (2q13) with the nuclear receptor, peroxisome
proliferator-activated receptor _ (PPARG). PPARG is located in a breakpoint
hot spot region, leading to recurrent alterations of this gene in thyroid tumorsof follicular origin including carcinomas as well as adenomas with or without
involvement of PAX8.

The gene ‘phosphatase and tensin homolog’ (PTEN), is a tumor suppressor locatedat chromosome region 10q23, that plays an essential role in the maintenanceof chromosomal stability, cell survival and proliferation. Loss of PTEN has beenfound in a wide number of tumors, and its important role is demonstrated by thefact that it is the second most frequently mutated gene after TP53. Loss of PTEN
significantly correlates with the advanced forms of gliomas, but also of prostatecancer and breast tumors.

A break or split probe for PPARG is best used to analyze translocation of the
PPARG (3p25) gene on formalin fixed paraffin embedded tissue for routine clinicaldiagnosis.

The PTEN (10q23) FISH probe is optimized to detect copy numbers of the PTEN
gene region at region 10q23. The Chromosome 10 Satellite enumeration probe (SE10) at D10Z1 is included to facilitate chromosome identification.

The PPARG (3p25) Break probe is optimized to detect translocations andamplification involving the PPARG gene region at 3p25 in a dual_color, split assay.

REFERENCES
Cairns et al, 1997, Cancer Res, 57 ; 4997-5000.
Hermans et al, 2004, Genes Chrom Cancer, 39; 171-184.

REFERENCES
French et al, 2003, Am J Pathol, 162; 1053-1060.
Drieschner et al, 2006, Thyroid, 16; 1091-1096.

RH113215

3p25

D3S1351

D10Z1

325 kB

480 kB

RH11148

PPARG

RH47435

10q23

350 kBPTEN

SHGC-143153

D3S65610

3* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

206

A

D

V

A

N

C

E

D

S

T

A

I

N

I

RARA Break

N

G

-

I

V

D

P

R

O

B

E

S

RB1
RARA (17q21) Break probehybridized to patient material
showing a translocation at
17q21 (1RG1R1G).

RB1 (13q14) probehybridized to a normal
metaphase (2G).

RARA (17q21) BreakRB1 (13q14)

CODE

COLOR

FORMATSTATUS

KBI-10305

Green/Red

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-40001

Green

10 test

IVD

MENU

MENU

HEMATOPATHOLOGYPRENATALBACKGROUNDBACKGROUNDThis break apart probe can detect the numerous types of recurrent rearrangementof the RAR_ (Retinoid acid receptor, alpha) gene with various gene partners(e.g., PML, NPM, MLL, FIP1L1, NuMA1, PLZF, amongst the others), leading to
the formation of different reciprocal fusion proteins. The importance of retinoid
metabolism in acute promyelocytic leukemia (APL) is highlighted by the numerous
recent studies, but the different leukemogenic functions of the RAR_ fusion
proteins in the neoplastic myeloid development still has to be defined, as well as
the distinct clinical outcome of the patients with the variant forms of APL.

The chromosome 13 specific region probe is optimized to detect copy numbers ofchromosome 13 at 13q14.2 on uncultered amniotic cells. In all PN combinations
the 13q14 specific FISH probe is direct-labeled in green with PlatinumBright 495.
D13S1195

13q14

REFERENCES

RB1

910 kB

D13S740

Grimwade et al, 2000, Blood 96; 1297-1308.

13

RH69066

530 kB
RH54996
17q21

RARA
RH17717610 kB

17

D17S1196* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
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207

A

D

V

A

N

C

E

D

S

T

A

I

N

I

RB1 / RCAN1

N

G

-

I

V

D

P

R

O

B

E

S

RB1 / RCAN1, SE X/SE Y/ SE 18
RB1 (13q14)/RCAN1 (21q22)
probe hybridized to a normalinterphase (2R2G).

RB1 (13q14) / RCAN1 (21q22), SE X (DXZ1) / SE Y (DYZ3) / SE
18 (D18Z1)
CODE

COLOR

FORMATSTATUS

KBI-40005

Green/Red/Blue

10 testIVD

KBI-40006

Green/Red/Blue

30 testIVD

KBI-40007

Green/Red/Blue

50 testIVD

MENU
PRENATAL

RB1 (13q14) / RCAN1 (21q22)
CODE

COLOR

FORMATSTATUS

KBI-40003

Green/Red

10 testIVD

BACKGROUND
Trisomy 21 is one of the most common chromosomal abnormalities in live bornchildren and causes Down syndrome.

MENU

Trisomy 13, also called Patau syndrome, is a chromosomal condition that is
associated with severe mental retardation and certain physical abnormalities.
Trisomy 18 causing Edwards syndrome is the second most common autosomal
trisomy after trisomy 21. The disorder/condition is characterized by severe
symptoms. Turner syndrome occurs when females inherit only one X chromosome;their genotype is X0. Metafemales or triple-X females, inherit three X of
more chromosomes. Klinefelter syndrome males inherit one or more extra X
chromosomes; XYY syndrome males inherit an extra Y chromosome.

PRENATALBACKGROUND
Trisomy 21 is one of the most common chromosomal abnormalities in live bornchildren and causes Down syndrome. Molecular analysis has revealed thatthe 21q22.1-q22.3 region appears to contain the gene(s) responsible for thecongenital heart disease observed in Down syndrome. Trisomy 13, also called
Patau syndrome, is a chromosomal condition that is associated with severe
mental retardation and certain physical abnormalities. The critical region has beenreported to include 13q14-13q32 with variable expression, gene interactions,orinterchromosomal effects. The RCAN1 (21q22) specific FISH probe is optimized
to detect copy numbers of chromosome 21 at 21q22 on uncultured amniotic cells.
The RB1 (13q14) specific FISH probe is optimized to detect copy numbers ofchromosome 13 at 13q14 on uncultured amniotic cells.

REFERENCES
Uchida et al, 2010, Cancer Genet Cytogenet, 203; 324-327.
Sen et al, 2002, J of Nat Canc Inst, 94; 1320-1329.
Lassmann et al, 2007, Clin Cancer Res, 13; 4083-4091.

13q14
D21S1705

D13S1195

13q14

RB1

21q22

910 kB

21

RCAN1

D21S1705

D13S1195

RB1

21q22

910 kB

21

RCAN1
RH92717

D13S740650 kB

13

RH92717

D13S740

13

DYZ3

D18Z1

DXZ1

Y

18

X

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
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208

650 kB

A

D

V

A

N

C

E

D

S

T

A

I

N

I

RCAN1

N

G

-

I

V

D

P

R

O

B

E

S

RCAN1 / SE X / SE Y
RCAN1 (21q22) probehybridized to a normal
metaphase (2R).

Hybridization of the RCAN1(21q22), SE X, SE Y probe toa male metaphase spreadshowing normal pattern(2R1G1B)

RCAN1 (21q22)

RCAN1 (21q22), SE X, SE Y

CODE

COLOR

FORMATSTATUS

KBI-40002

Red

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-40008

Green/Red/Blue

20 testIVD

KBI-45008

Green/Red/Blue

5 testIVD

MENU
PRENATALMENU
PRENATALBACKGROUNDBACKGROUND

The chromosome 21 specific region probe is optimized to detect copy numbers ofchromosome 21 at 21q22.1 on uncultured amniotic cells. In all PN combinations
the 21q specific FISH probe is direct-labeled in red with PlatinumBright 550.

Chromosomal abnormalities involving the X and Y chromosome (sexchromosomes) are slightly less common than autosomal abnormalities andare usually much less severe in their effects. The high frequency of people with
sex chromosome aberrations is partly due to the fact that they are rarely lethal
conditions.

D21S1705

21q22

21

RCAN1

650 kB- Turner syndrome occurs when females inherit only one X chromosome - their
genotype is X0.

RH92717- Metafemales or triple-X females, inherit three X chromosomes - their genotype is
XXX or more rarely XXXX or XXXXX.
- Klinefelter syndrome males inherit one or more extra X chromosomes - their
genotype is XXY or more rarely XXXY, XXXXY, or XY / XXY mosaic.
D21S1705

21q22

21

RCAN1

DYZ3
650 kB
DXZ1

RH92717Y

X* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

209

A

D

V

A

N

C

E

D

S

T

A

I

N

I

RET Break

N

G

-

I

V

D

P

R

O

B

E

S

ROS1 BreakHybridization of RET breakprobe to a tissue section
showing abarrant pattern(1RG1R1G).

Hybridization of ROS1 (6q22)
Break Probe (KBI-10752) toa tissue section harboring a
ROS1 rearrangement.

RET (10q11) BreakROS1 (6q22) Break

CODE

COLOR

FORMATSTATUS

KBI-10753

Green/Red

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-10752

Green/Red

10 test

IVD

MENU

MENU

LUNG PATHOLOGYLUNG PATHOLOGYBACKGROUNDBACKGROUND

Pericentric inversion of chromosome 10 involving the RET (ret proto-oncogene)
gene at chromosome 10q11 is known to increase expression of the RET gene byfusion with KIF5B (10p11). Translocations with other fusion partners have also
been described. Elevated expression of RET is observed in non-small cell lungcancer (NSCLC), in which the function of tyrosine kinase-based therapeutics isbased on the inhibition of such fusion proteins. Translocations involving RET havealso been described in thyroid carcinomas.

Translocations involving the ROS1 gene at chromosome 6q22 can increase
expression of the gene by fusion with SLC34A2 (4p15), but also with other fusion
partners. Elevated expression is observed in non-small cell lung cancer (NSCLC),
where the success of tyrosine kinase-based therapeutics like Crizotinib (Xalkori)is based on inhibiting the activity of these fusion genes. The fusion of ROS1 to the
GOPC (FIG) gene, by deletion of a 240 kb DNA fragment, also results in activationof a fusion gene.

The RET (10q11) Break probe is optimized to detect translocations involving the
RET gene region at 10q11.

The ROS1 (6q22) Break probe is optimized to detect translocations involving
the ROS1 gene region at the 6q22 locus, as well as the 240 kb deletion forming
the ROS1-GOPC fusion gene, in a dual-color assay on formalin- fixed paraffinembedded tissue samples.

REFERENCES
Chen et al, Cancer Genet Cytogenet, 2007, 178: 128-134.
Kohno et al, Nat Med, 2012, 18: 375-377.
Takeuchi et al, Nat Med, 2012, 18: 378-381.

REFERENCES
Charest et al, Genes Chromosomes Cancer, 2003, 37: 58-71.
Rikova et al, Cell, 2007, 131: 1190-120.
Rimkunas et al, Clin. Can. Res., 2012, 18: 4449-4457.
Takeuchi et al, Nat. Med., 2012, 18: 378-381.
Gu et al, PLoS, 2011, 6: e15640.

RH51277535 kB
RET

10q11.2GDB:579598
D10S1176

500 kB
SHGC-14420
SHGC-148579

450 kB

10
RH69070

ROS1

RH104060

Exon 42
Exon 30

6q22

260 kB
RH68126GOPC

6* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

210

A

D

V

A

N

C

E

D

S

T

A

I

N

I

RUNX1 / RUNX1T1

N

G

-

I

V

D

P

R

O

B

E

SE 18 (D18Z1)
Hybridization of RUNX1/
RUNX1T1 fusion probe to a
metaphase spread showing
normal pattern (2R2G).

SE 18 (D18Z1)
CODE

COLOR

FORMATSTATUS

KBI-20018BBlue

10 testIVD

MENUCONSTITUTIONALBACKGROUND
The chromosome 18 specific Satellite Enumeration (SE 18) FISH probe (D18Z1)
is optimized to detect copy numbers of chromosome 18 at 18p11-18q11 on
uncultured amniotic cells. In all PN combinations the 18 SE centromeric FISH
probe is offered direct-labeld in blue with PlatinumBright415.

RUNX1 / RUNX1T1 t(8;21) Fusion
CODE

COLOR

FORMATSTATUS

KBI-10301

Green/Red

10 testIVD

MENU
HEMATOPATHOLOGYBACKGROUNDt(8;21)(q21;q22) is the most frequently observed karyotypic abnormality
associated with acute myeloid leukemia (AML), especially in FAB M2. As aconsequence of the translocation the RUNX1 (previously known as AML) (CBFA2)
gene in the 21q22 region is fused to the RUNX1T1 (previously known as ETO)
(MTG8) gene in the 8q21 region, resulting in one transcriptionally active gene on
the 8q-derivative chromosome.
The RUNX1 / RUNX1T1 t(8;21)(q21;q22) specific FISH probe is optimized to detect
the reciprocal translocation t(8;21) in a dual-color, dual-fusion assay.
REFERENCES
Sacchi et al, 1995, Genes Chrom Cancer, 79; 97-103.
Hagemeijer et al, 1998, Leukemia, 12; 96-101.

D21S325
SHGC-102339

RUNX1T1
(ETO)

21q22

1190 kB

21

8q21.3

RUNX1(AML1)

1380 kB

SHGC-9898

SHGC-1268

8* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
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S

A

D

V

A

N

C

E

D

S

T

A

I

N

I

SE 7 / SE 8

N

G

-

I

V

D

P

R

O

B

E

S

SE X / SE Y
Hybridization of SE 7 / SE
8 probe to a metaphasespread showing normal
pattern (2R2G).

Hybridization of SE X / SE Y
probe to a male metaphasespread showing normal
pattern (1R1G).

SE 7 (D7Z1) / SE 8 (D8Z1)

SE X (DXZ1) / SE Y (DYZ3)

CODE

COLOR

FORMATSTATUS

KBI-20031

Green/Red

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-20030

Green/Red

10 test

IVD

MENU

MENU

CONSTITUTIONALCONSTITUTIONALBACKGROUNDBACKGROUND

Trisomy 8 is found as one of the genetic changes in CML, while loss ofchromosome 7 is found in AML. The SE 7 (D7Z1) / SE 8 (D8Z1) FISH probes are
optimized to detect repetitive sequences located in the pericentric heterochromatinof chromosome 7 and 8.

Chromosomal abnormalities involving the X and Y chromosome (sexchromosomes) are slightly less common than autosomal abnormalities andare usually much less severe in their effects. The high frequency of people with
sex chromosome aberrations is partly due to the fact that they are rarely lethal
conditions.
- Turner syndrome occurs when females inherit only one X chromosome - their
genotype is X0.

D8Z1
D7Z1

- Metafemales or triple-X females, inherit three X chromosomes - their genotype is
XXX or more rarely XXXX or XXXXX.
- Klinefelter syndrome males inherit one or more extra X chromosomes - their
genotype is XXY or more rarely XXXY, XXXXY, or XY / XXY mosaic.

8
7

DYZ3

DXZ1

Y

X

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
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A

D

V

A

N

C

E

D

S

T

A

I

N

I

SE X / SE Y / SE 18

N

G

-

I

V

D

P

R

O

B

E

S

SHOX / SE X
Hybridization of SE X / SE Y /SE 18 probe to a metaphasespread showing normal
pattern (1R1G2B).

Short Stature SHOX (Xp22)/ SE X probe hybridized to amale metaphase (2R1G).

SE X (DXZ1) / SE Y (DYZ3) / SE 18 (D18Z1)

Short Stature SHOX (Xp22) / SE X

CODE

COLOR

FORMATSTATUS

KBI-20032

Green/Red/Blue

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-40112

Green/Red

10 testIVD

KBI-45112

Green/Red

5 testIVD

MENUCONSTITUTIONALMENU
POSTNATALBACKGROUNDBACKGROUND

Chromosomal abnormalities involving the X and Y chromosome (sexchromosomes) are slightly less common than autosomal abnormalities andare usually much less severe in their effects. The high frequency of people with
sex chromosome aberrations is partly due to the fact that they are rarely lethal
conditions.

Individuals with SHOX-related short stature have disproportionate short stature
and/or wrist abnormalities consistent with those described in Madelung deformity.
The SHOX genes located on the pseudoautosomal regions of the X and Y
chromosomes are the only genes known to be associated with SHOX-related
haploinsufficiency.

- Turner syndrome occurs when females inherit only one X chromosome - their
genotype is X0.

The SHOX region probe is optimized to detect copy numbers of the SHOX generegion at Xp22. The chromosome X Satellite Enumeration (SE X) FISH probe at
DXZ1 is added to facilitate chromosome identification.

- Metafemales or triple-X females, inherit three X chromosomes - their genotype is
XXX or more rarely XXXX or XXXXX.

REFERENCES- Klinefelter syndrome males inherit one or more extra X chromosomes - their
genotype is XXY or more rarely XXXY, XXXXY, or XY / XXY mosaic.

Rao et al, 1997, Hum. Genet., 100; 236-239.
Morizio et al, 2003, Am. J. Med. Genet., 119; 293-296.

DYZ3

D18Z1

Xp22.3 / Yp11.3

DXZ1
DXYS153

Y

18

DXZ1

Y

SHOX

190 kBDXYS130

X
X* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
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A

D

V

A

N

C

E

D

S

T

A

I

N

I

SNRPN / PML

N

G

-

I

V

D

P

R

O

B

E

S

SRD / SE 1
Prader-Willi SNRPN (15q11)/ PML (15q24) probehybridized to a normalinterphase/metaphase(2R2G).

SRD (1p36) / SE 1 probehybridized to a normal
metaphase (2R2G).

SRD (1p36) / SE 1 (1qh)

Prader-Willi SNRPN (15q11) / PML (15q24)
CODE

COLOR

FORMATSTATUS

KBI-40109

Green/Red

10 testIVD

KBI-45109

Green/Red

5 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-10712

Green/Red

10 test

IVD

MENU
MENU

NEUROPATHOLOGYPOSTNATALBACKGROUNDBACKGROUND

Neuroblastomas frequently have deletions of chromosome 1p and amplificationof the MYCN oncogene. These deletions tend to be large and extend to thetelomere, but a common region within sub-band 1p36.3 is consistently lost in thesedeletions. Inactivation of a tumor suppressor gene within 1p36.3 is believed to be
associated with an increased risk for disease relapse.

Prader-Willi Syndrome (PWS) is a clinically distinct disorder including
diminished fetal activity, obesity, hypotonia, mental retardation, short stature,hypogonadotropic hypogonadism, strabismus, and small hands and feet.
Approximately 70% of cases of PWS arise from paternal deletion of the 15q11-q13
region including the gene SNRPN (small nuclear ribonucleoprotein polypeptide N).
The PWS SNRPN region probe is optimized to detect copy numbers of the SNRPN
gene region at 15q11. The PML (promyelocytic leukemia) gene specific FISH probe
at 15q24 is included as control probe.

The SRD (1p36) FISH probe is optimized to detect copy numbers of the 1p36 region
on chromosome 1. The chromosome 1 satellite enumeration probe (SE 1) at 1qh is
included to facilitate chromosome identification.
REFERENCES
Caron et al, 1993, Nat Genet, 4: 187-190.
Cheng et al, 1995, Oncogene, 10: 291-297.
White et al, 2005, Oncogene, 24: 2684-2694.

REFERENCES
Knoll et al, 1989, Am. J. Med. Genet., 32; 285-290.
Ozcelik et al, 1992, Nat. Genet., 2; 265-269.

1p36.3

D15S677

SNRPN

SHGC-149299

220 kB

530 kB

D15S631E

CHD5

15q11.2

SHGC-108153

UBE3A
1qh
15q24

15

PML
SHGC-152035

180 kB
W1870

1* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
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214

A

D

V

A

N

C

E

D

S

T

A

I

N

I

SS18 Break

N

G

-

I

V

D

P

R

O

B

E

S

STS / KAL1 / SE X
SS18 (18q11) Break probehybridized to patient material
showing translocation of the
SYT (SS18) gene region at
18q11 (1RG1R1G).

STS (Xp22) / KAL1 (Xp22)/ SE X Triple-Color probehybridized to male patientmaterial showing a deletionof the STS gene region(1R1B).

Material kindly provided by
Necker hospital, Paris.

SS18 (18q11) BreakSTS (Xp22) / KAL1 (Xp22) / SE X Triple-Color

CODE

COLOR

FORMATSTATUS

KBI-10713

Green/Red

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-40115

Green/Red/Blue

10 testIVD

KBI-45115

Green/Red/Blue

5 testIVD

MENUSOFT TISSUE PATHOLOGYMENUPOSTNATALBACKGROUNDBACKGROUND

The characteristic chromosomal abnormality in Synovial Sarcoma t(X;18)(p11.2;q11.2) is present in 90% of the patients. This translocation results in thefusion of the synovial sarcoma translocation, chromosome 18 (SS18) gene toeither of two distinct genes, SSX1 or SSX2, located on the X chromosome.

STS (Steroid Sulfatase) disease is a chromosome X-linked disorder associatedwith a microdeletion of the gene within the Xp22.3 region. Deletion of the steroid
sulfatase gene has been detected in individuals with recessive X-linked ichtyosis,
the disease been considered one of the most frequent human enzyme deficientdisorders. KAL1 (Kallmann syndrome interval gene-1) maps to the Kallmann
syndrome critical region on the distal short arm of the human X chromosome.
Individuals with Kallmann syndrome suffers of hypogonadotropic hypogonadism
and anosmia, with clinical features of variable phenotype. It affects approximately
1 in 8000 males and 1 in 40000 females.

The SS18 (18q11) Break probe is optimized to detect translocations involving the
SS18 gene region at 18q11 in a dual-color, split assay on paraffin embedded tissue
sections.
REFERENCES
Kawai et al, 1998, NEJM, 338; 153-160.
Surace et al, 2004, LabInvest., 84; 1185-1192.

The STS (Xp22) region probe is optimized to detect copy numbers of the STS
gene region at Xp22. The KAL1 (Xp 22) region probe is optimized to detect
copy numbers of the KAL1 gene region at Xp22. The Chromosome X Satellite
Enumeration (SE X) FISH probe at DXZ1 is included to facilitate chromosome
identification.

SHGC-140887

1030 kB
18q11.2

SGC35446

SS18
RH79212REFERENCES

690 kB

18

Alper in et al, 1997, J. Biol. Chem., 272; 20756-20763.
Meroni et al, 1996, Hum. Mol. Genet., 5; 423-431.

SHGC-84255

Xp22.3

DXS1130STS

DXZ1

400 kB

RH66689
Gap: 1 MB
AFM309YC1

KAL1

330 kBDXS7716X* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
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A

D

V

A

N

C

E

D

S

T

A

I

N

I

TBX1 / SHANK3

N

G

-

I

V

D

P

R

O

B

E

S

TERC / 3q11
DiGeorge TBX1 (22q11)/ 22q13 (SHANK3) probehybridized to DiGeorge
patient material showing adeletion of the TBX1 generegion at 22q11 (1R2G).

TERC (3q26) / 3q11 probehybridized to a normalinterphase/metaphase(2R2G).

Image kindly provided by Dr.
F. Girard- Lemaire Service
de Cytogénétique (Dr. Flori),
CHU Strasbourg.

TERC (3q26) / 3q11

DiGeorge TBX1 (22q11) / 22q13 (SHANK3)
CODE

COLOR

FORMATSTATUS

KBI-40104

Green/Red

10 testIVD

KBI-45104

Green/Red

5 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-10110

Green/Red

10 test

IVD

MENU
MENU

HEMATOPATHOLOGYPOSTNATALBACKGROUNDBACKGROUND

Amplification of the 3q26-q27 has a high prevalence in cervical, prostate, lung, andsquamous cell carcinoma. This amplification can also be found to a lesser extent
in CLL patients. The minimal region of amplification was refined to a 1- to 2-Mb
genomic segment containing several potential cancer genes including TERC, thehuman telomerase RNA gene.

The 22q11 deletion in DiGeorge syndrome/VCFS is characterized by defects in thederivatives of the pharyngeal apparatus. TBX1, a member of the T-box transcription
factor family, is required for normal development of the pharyngeal arch arteries.
Haploinsufficiency of TBX1 has been demonstrated to be sufficient to generate atleast one important component of the DiGeorge syndrome phenotype in mice. The
TBX1 is also located within the minimal critical DiGeorge region in humans.

The TERC (3q26) specific FISH probe is optimized to detect copy numbers of the
TERC (previously known as hTERC) gene region at region 3q26. The 3q11 region
probe is included to facilitate chromosome identification.

The DiGeorge TBX1 region probe is optimized to detect copy numbers of the TBX1
gene region at 22q11.2. The subtelomeric (ST) 22qter FISH probe is included ascontrol probe. The SHANK3 FISH probe at 22q13 is serving as internal control.

REFERENCES
Arnold et al, 1996, Genes Chrom Cancer, 16; 46-54.
Soder et al, 1997, Oncogene, 14; 1013-1021.

REFERENCES
Lindsay et al, 2001, Nature, 410; 97-101.
Merscher et al, 2001, Cell, 104; 619-629.
Paylor et al, 2006, PNAS, 103; 7729-7734.

SHGC-102405

640 kB
HIRA
3q11.2

LINC00879
SHGC-141087

D22S1624
RH17919

TBX1

230 kB

22q11.2

22590 kB

3q26.2

RH47909

TERC

22q13
RH84573ARSA

RH10606

130 kBSHANK3
RH38881* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
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A

D

V

A

N

C

E

D

S

T

A

I

N

I

TERC / MYC / SE 7

N

G

-

I

V

D

P

R

O

B

E

TERT / 5q31
TERC (3q26) / MYC (8q24)/ SE 7 Triple-Color probehybridized to a PAP smear(destained) showing 3q26
and 8q24 amplification. The
SE 7 control probe indicatesa non-triploid karyotype (2B).

TERT (5p15) / 5q31 probehybridized to a normalinterphase/metaphase(2R2G).

Image kindly provided by Dr.
Weimer, Kiel.

Image kindly provided by Dr.
Mohr, Dresden.

TERC (3q26) / MYC (8q24) / SE 7 Triple-ColorTERT (5p15) / 5q31

CODE

COLOR

FORMATSTATUS

KBI-10704

Green/Red/Blue

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-10208

Green/Red

10 test

IVD

MENU

MENU

GYNEPATHOLOGYHEMATOPATHOLOGYBACKGROUNDBACKGROUND

The most consistent chromosomal gain in aneuploid tumors of cervical squamouscell carcinoma mapped to chromosome arm 3q, including the human telomerase
gene locus (TERC) at 3q26. Highlevel copy number increases were also mapped tochromosome 8. Integration of HPV (Human Papilloma Virus) DNA sequences into
MYC chromosomal regions have been repeatedly observed in cases of invasive
genital carcinomas and in cervical cancers.

The TERT / 5q31 dual-color FISH probe can be used to detect deletions involving
band 5q31 in MDS and RUNX1.
The 5q- specific FISH probe is optimized to detect copy numbers at the CDC25C /EGR1 gene region at 5q31. The TERT (previously known as hTERT) gene region at
5p15 is included to facilitate chromosome identification.
REFERENCES

The TERC (3q26) FISH probe is optimized to detect copy numbers of the TERC
gene region at region 3q26. The MYC (8q24) FISH probe is optimized to detect
copy numbers of the MYC gene region at 8q24. The chromosome 7 satellite
enumeration probe (SE 7) at D7Z1 is included as ploidy control.

Zhao et al, 1997, PNAS, 94; 6948-6053.
Horrigan et al, 2000, Blood, 95; 2372-2377.
5p15.3
SHGC-154319

REFERENCES

TERT

Xie et al, 2008, Geburtshilfe Frauenheilkunde, 68: 573.
Heselmeyer et al, 1996, PNAS, 93: 479-484.
Herrick et al, 2005, Cancer Res, 65: 1174-1179.

390 kB

D5S2269E

RH48032

CDC25C
650 kB

5q31

EGR1
SHGC-3896

RH779665
540 kB
RH17919MYC
590 kB

3q26.2

8q24.2
SHGC-144185

8

TERC
RH10606

3

D7Z1

7

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
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S

A

D

V

A

N

C

E

D

S

T

A

I

N

I

TERT / 5q31 (tissue)

N

G

-

I

V

D

P

R

O

B

E

S

TFE3 BreakHybridization of TERT / 5q31
Probe to a tissue section
showing gain of the TERT
region.

TFE3 (Xp11) Break probehybridized to renal cell
carcinoma showing atranslocation at Xp11
(1RG1R1G).

Image kindly provided by Dr.
Desangles, Paris.

TERT (5p15) / 5q31 (tissue)

TFE3 (Xp11) Break

CODE

COLOR

FORMATSTATUS

KBI-10709

Green/Red

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-10741

Green/Red

10 test

IVD

MENU

MENU

LUNG PATHOLOGYHEAD, NECK AND ENDOCRINE PATHOLOGYBACKGROUNDBACKGROUND

Amplifications of the TERT gene at 5p15 has been observed in a variety of cancers,
particularly lung cancer, cervical tumors, and breast carcinomas. Several studies
have revealed a high frequency of TERT gene amplification in human tumors,which indicates that the TERT gene may be a target for amplification during thetransformation of human malignancies and that this genetic event probably
contributes to a dysregulation of TERT / telomerase occurring in a subset of humantumors.

Abnormalities of Xp11.2 region have often been observed in papillary renal cell
carcinomas and are sometimes the sole cytogenetic abnormality present. The
transcription factor binding to IGHM enhancer 3 (TFE3) gene, which encodesa member of the helix-loop-helix family of transcription factors, is located inthis critical region and can be fused to various other chromosomal regions bytranslocation. Known fusion partners are NONO (Xq12), PRCC (1q21), SFPQ (1p34),
CLTC (17q23) and ASPSCR1 (17q25).

The TERT (5p15) FISH probe is designed as a dual-color assay to detect
amplification at 5p15. The CDC25C / EGR1 (5q31) gene region probe is included asinternal control.

The TFE3 (Xp11) Break probe is optimized to detect translocations involving theTFE3 gene region at Xp11.2 in a dual-color, break assay.
REFERENCESREFERENCES

Sidhar et al, 1996, Hum Mol Genet, 5; 1333-1338.
Weterman et al, 1996, Proc Natl, Acad Sci, 93; 15294-15298.

Bryce et al, 2000, Neoplasia, 2;197-201.
Zhang et al, 2000, Cancer Res, 60;6230-6235

RH66279
5p15.3
SHGC-154319

530 kB
Xp11.2TERT

RH18187

390 kB

TFE3

D5S2269E

RH103001

450 kB
RH48032
DXS1522

CDC25C
650 kB

5q31

X

EGR1
SHGC-3896

5* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
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A

D

V

A

N

C

E

D

S

T

A

I

N

I

TMPRSS2-ERG

N

G

-

I

V

D

P

R

O

B

E

TOP2A / ERBB2 / SE 17
TMPRSS2-ERG (21q22)
rearrangement probehybridized to prostate
carcinoma tissue showing
a deletion of the TMPRSS2(21q22) gene region
associated with TMPRSS2ERG fusion (1RGB 1RB).

TOP2A (17q21) / ERBB2(17q12) / SE 17 TC probehybridized to breast tumor
tissue showing amplificationof TOP2A / ERBB2.

Image kindly provided by Dr.
Teixeira, Porto.

TMPRSS2-ERG (21q22) Deletion, Break, Triple-Color

TOP2A (17q21) / ERBB2 (17q12) / SE 17, Triple-Color

CODE

COLOR

FORMATSTATUS

KBI-10726

Green/Red/Blue

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-10735

Green/Red/Blue

10 test

IVD

MENU

MENU

UROPATHOLOGYBREAST PATHOLOGYBACKGROUNDBACKGROUND

The transmembrane protease serine 2 gene (TMPRSS2) is involved in genefusions with ERG, ETV1 or ETV4 in prostate cancer. It has been reported that theexpression of the TMPRSS2-ERG fusion gene is a strong prognostic factor for therisk of prostate cancer recurrence in prostate cancer patients treated by surgery.

The presence of both TOP2A amplification and deletion in advanced cancer areassociated with decreased survival, and occur frequently and concurrently with
ERBB2 gene amplification (commonly refered to as HER2).
The TOP2A (17q21) / ERBB2 (17q12) / SE 17 probe is designed as a triple-color
assay to detect amplification at 17q12 as well as amplifications or deletions at
17q21. The chromosome 17 satellite enumeration probe (SE 17) at D17Z1 in blueis included to facilitate chromosome identification/enumeration.

The TMPRSS2-ERG rearrangement probe is optimized to detect the deletion
between TMPRSS2 and ERG at 21q22 associated with the TMPRSS2-ERG fusion ina triple-color deletion assay.
It also detects translocations involving the TMPRSS2 region such as ETV1 t(7;21),or ETV4 t(17;21).

REFERENCES
Järvinen et al, 1999, Genes Chromosomes Cancer 26; 142-150.
Järvinen et al, 2000, Am. J. Pathology 156; 639-647.

REFERENCES
Perner et al, 2006 Cancer Res 66; 8337-8341.
Hermans et al, 2006, Cancer Res 66; 10658-10663.
Attard et al, 2008, Oncogene 27; 253-263.

SHGC-85693

D17Z1

ERBB2

460 kB

17q12
SHGC-85350

D17S1179
17q21

730 kB

RH54996

SHGC-106749

ERG
ETS2

17

GAP 2.3 MB

TOP2A

370 kB

D21S34921

630 kB

21q22

S

WI-9139

RH13802

TMPRSS2
SHGC-156046

700 kB
RH5200* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
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A

D

V

A

N

C

E

D

S

T

A

I

N

I

TOP2A / SE 17

N

G

-

I

V

D

P

R

O

B

E

S

TP53 / ATM
TOP2A (17q21) / SE 17
probe hybridized to breast
tissue (2R2G).

TP53 (17p13) / ATM (11q22)
hybridized to a normal
metaphase (2R2G).

TOP2A (17q21) / SE 17

TP53 (17p13) / ATM (11q22)

CODE

COLOR

FORMATSTATUS

KBI-10724

Green/Red

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-10114

Green/Red

10 test

IVD

MENU

MENU

BREAST PATHOLOGYHEMATOPATHOLOGYBACKGROUNDBACKGROUNDThe Topoisomerase2A (TOP2A) enzyme, which is vital for the cell because of
its role in cell replication and repair, catalyzes the relaxation of supercoiled DNA
molecules to create a reversible double-strand DNA break. This enzyme is also thetarget of a number of cytotoxic agents, namely TOP2A inhibitors (anthracyclines,
etoposide, teniposide).

Deletion of TP53 (previously known as p53) and ATM are both indicating poor
prognosis in CLL. Alterations of the TP53 (17p13) gene occur not only as somatic
mutations in human malignancies, but also as germline mutations in some cancerprone families with Li-Fraumeni syndrome. Deletions of TP53 are frequent in CLL
and MM, usually associated with unfavorable prognosis. Deletions of the long armof chromosome 11 (11q) are one of the most frequent structural chromosome
aberrations in various types of lymphoproliferative disorders. A critical genomic
region located in bands 11q22.3-q23.1 has been identified and contains among
other genes the ATM (ataxia telangiectasia mutated) gene.

The TOP2A (17q21) / SE 17 FISH probe is optimized to detect amplifications (copynumbers) or deletions of the TOP2A gene region at the 17q21. The chromosome
17 satellite enumeration probe (SE 17) at D17Z1 is included to facilitate
chromosome identification.

REFERENCESREFERENCES

Boultwood J, 2001, J. Clin. Pathol., 54; 512-516.
Amiel A et al, 1997, Cancer Gener.Cytogenet,, 97; 97-100.
Drach J et al, 1998, Blood, 92; 802-809.
Doehner H et al, 1997, Blood, 7; 2516-2522.

Järvinen et al, 1999, Genes Chromosomes Cancer 26; 142-150.
Järvinen et al, 2000, Am. J. Pathology 156; 639-647.

D17Z1

RH54996
17p13
D17S960

17q21

370 kB
TOP2A

335 kB

D11S448517

WI-9139

TP53

D17S634ATM
11q22

235 kB

17

RH39918

11* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

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V

A

N

C

E

D

S

T

A

I

N

I

TP53 / MPO

N

G

-

I

V

D

P

R

O

B

E

S

TP53 / SE 17
TP53 (17p13) / MPO (17q22)“ISO 17q” probe hybridized
to peripheral blood ofa CLL patient with anisochromosome 17 (3R1G).

TP53 (17p13) / SE 17 probehybridized to patient material
showing a 17p13 deletionat the TP53 gene region(1R2G).

Image kindly provided by Dr.
Lana Harder, Kiel.

TP53 (17p13) / MPO (17q22) “ISO 17q”

TP53 (17p13) / SE 17

CODE

COLOR

FORMATSTATUS

KBI-10011

Green/Red

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-10112

Green/Red

10 testIVD

KBI-12112

Green/Red

20 testIVD

MENU
HEMATOPATHOLOGYMENUHEMATOPATHOLOGYBACKGROUNDBACKGROUND

Isochromosome 17q is the most common isochromosome in cancer. It plays animportant role in tumor development and progression. Hematologic malignancies
such as chronic myeloid leukemia (CML) with isochromosome 17q carry a poor
prognosis. Isochromosome 17q is the most common chromosome abnormality inprimitive neuroectodermal tumors and medulloblastoma. Isochromosome 17q is,by convention, symbolized as i(17q).

The TP53 tumor suppressor gene at 17p13, has been shown to be implicated in
the control of normal cellular proliferation, differentiation, and apoptosis. Allelicloss, usually by deletion, and inactivation of TP53 have been reported in numerous
tumor types and are associated with poor prognosis in CLL.
The TP53 (17p13) FISH probe is optimized to detect copy numbers of the TP53
gene region at 17p13. The chromosome 17 satellite enumeration probe (SE 17) at
D17Z1 is included to facilitate chromosome identification. Kreatech has developed
this probe for the specific use on cell material (KBI-10112 / KBI-12112), or for theuse on tissue (KBI-10738).

The TP53 (17p13) / MPO (17q22) “ISO 17q” FISH probe is optimized to detect copy
numbers of the TP53 gene region at 17p13 and MPO gene region at 17q22. In caseof i(17q) a signal pattern of three red signals for MPO (17q22) and one signal for
TP53 at 17p13 is expected.
REFERENCESREFERENCES

Becher et al, 1990, Blood, 75; 1679-1683.
Fioretos et al, 1999, Blood, 94; 225-232.

Amiel A et al, 1997, Cancer Gener. Cytogenet, 97; 97-100.
Drach J et al, 1998, Blood, 92; 802-809.

D17S960

17p13

335 kB
17p13

D17S960

TP53

D17Z1

D17S634

335 kB
TP53

RH55183

D17S634
17q22

17

MPO

17

500 kB

SHGC-144222* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

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I

TP53 / SE 17 (tissue)

N

G

-

I

V

D

P

R

O

B

E

S

UBE3A / PML
Hybridization of TP53
probe to a tissue section
showing normal pattern(2R2G).

Angelman UBE3A (15q11)/ PML (15q24) probehybridized to a normalinterphase/metaphase(2R2G).

TP53 (17p13) / SE 17 (tissue)

Angelman UBE3A (15q11) / PML (15q24)

CODE

COLOR

FORMATSTATUS

KBI-10738

Green/Red

10 test

IVD

CODE

COLOR

FORMATSTATUS

KBI-40110

Green/Red

10 testIVD

KBI-45110

Green/Red

5 testIVD

MENU
TUMOR DIFFERENTIATIONMENUPOSTNATALBACKGROUNDBACKGROUNDThe TP53 tumor suppressor gene at 17p13, has been shown to be implicated in
the control of normal cellular proliferation, differentiation, and apoptosis. Allelicloss, usually by deletion, and inactivation of TP53 have been reported in numerous
tumor types and are associated with poor prognosis in CLL.

Angelman syndrome (AS) is characterized by severe developmental delay ormental retardation, severe speech impairment, gait ataxia and/or tremulousnessof the limbs, and an unique behavior with an inappropriate happy demeanor that
includes frequent laughing, smiling, and excitability. In addition, microcephaly andseizures are common. AS is caused by absence of a maternal contribution to theimprinted region on chromosome 15q11-q13 including the UBE3A gene.

The TP53 (17p13) FISH probe is optimized to detect copy numbers of the TP53
gene region at 17p13. The chromosome 17 satellite enumeration probe (SE 17) at
D17Z1 is included to facilitate chromosome identification. Kreatech has developed
this probe for the specific use on cell material (KBI-10112 / KBI-12112), or for theuse on tissue (KBI-10738).

The AS UBE3A region probe is optimized to detect copy numbers of the UBE3A
gene region at 15q11. The PML (promyelocytic leukemia) gene specific FISH probe
at 15q24 is included as control probe.

REFERENCES
Amiel A et al, 1997, Cancer Gener.Cytogenet,, 97; 97-100.
Drach J et al, 1998, Blood, 92; 802-809.

REFERENCES
Matsuura et al, 1997, Nat. Genet., 15; 74-77.
Burger et al, 2002, Am. J. Med. Genet., 111; 233-237.

17p13
D17S960

D17Z1

335 kB

SNRPN

TP53

D15S1089

D17S63417

15q11.2

UBE3A

240 kB

D15S210

15q24

15

PML
SHGC-152035

180 kB
W1870* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

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D

V

A

N

C

E

D

S

T

A

I

N

I

WHSC1 / SE 4

N

G

-

I

V

D

P

R

O

B

E

S

XIST / SE X
Wolf-Hirschhorn WHSC1(4p16) / SE 4 probehybridized to WolfHirschhorn patient material
showing a deletion of the
WHSC1 gene region at 4p16
(1R2G).

X-Inactivation XIST (Xq13)/ SE X probe hybridized to amale metaphase (1R1G).

Image kindly provided by
Prof. Zollino, Rome.

Wolf-Hirschhorn WHSC1 (4p16) / SE 4

X-Inactivation XIST (Xq13) / SE X

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KBI-40107

Green/Red

10 testIVD

KBI-40108

Green/Red

10 testIVD

KBI-45107

Green/Red

5 testIVD

KBI-45108

Green/Red

5 test

IVD

MENU

MENU

POSTNATALPOSTNATALBACKGROUNDBACKGROUND

Wolf-Hirschhorn Syndrome (WHS) affected individuals have prenatal-onset growth
deficiency followed by postnatal growth retardation and hypotonia with muscle
under-development. Developmental delay/mental retardation of variable degree ispresent in all. FISH analysis using a WHSC1 specific FISH probe for chromosomal
locus 4p16.3 detects more than 95% of deletions in WHS.

The XIST locus is expressed only from the inactive X chromosome, resides
at the putative X inactivation center, and is considered a prime player in theinitiation of mammalian X dosage compensation. The severe phenotype of human
females whose karyotype includes tiny ring X chromosomes has been attributed
to the inability of the small ring X chromosome to inactivate. Many of the ring
chromosomes lack the XIST locus, consistent with XIST being necessary for cis
inactivation.

The Wolf-Hirschhorn region probe is optimized to detect copy numbers of the WolfHirschhorn critical region at 4p16. The chromosome 4 Satellite Enumeration (SE 4)
FISH probe at D4Z1 is included to facilitate chromosome identification.
REFERENCES

The XIST specific FISH probe is optimized to detect copy numbers of the XIST
region at Xq13. The chromosome X Satellite Enumeration (SE X) FISH probe at
DXZ1 is added to facilitate chromosome identification.

Gandelman et al, 1992, Am. J. Hum. Genet., 51; 571-578.
Wright et al, 1997, Hum. Mol. Genet., 6; 317-324.

REFERENCES
Migeon et al, 1993, PNAS, 90; 12025-12029.
Jani et al, 1995, Genomics, 27; 182-188.

4p16
RH18137

120 kB

D4Z1

DXZ1
D4S114

WHSC1

RH70575
Xq13

CHIC1
290 kB

DXS8235

X

4

XIST

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

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D

V

A

N

C

E

D

S

T

A

I

N

I

N

G

-

I

V

D

P

R

ZNF217 / 20q11
ZNF217 (20q13) / 20q11
probe hybridized to tissue(2R2G).

ZNF217 (20q13) / 20q11
CODE

COLOR

FORMATSTATUS

KBI-10733

Green/Red

10 testIVD

MENU
BREAST PATHOLOGYBACKGROUND
Zinc-finger protein 217 (ZNF217) is a Kruppel-like zinc-finger protein locatedat 20q13.2, within a region of recurrent maximal amplification in a variety oftumor types, and especially breast cancer cell lines and primary breast tumors.
Copy number gains at 20q13 are also found in more than 25% of cancers of theovary, colon, head and neck, brain, and pancreas. ZNF217 is considered a strong
candidate oncogene that may have profound effects on cancer progression, which
is transcribed in multiple normal tissues, and overexpressed in almost all cell lines
and tumors in which it is amplified.
The ZNF217 (20q13) FISH probe is optimized to detect copy numbers of 20q at
20q13. The 20q11 probe is included to facilitate chromosome identification.
REFERENCES
Tanner M et al, 2000, Clin Cancer Res, 6; 1833-1839.
Ginestier C et al, 2006, Clin Cancer Res, 12; 4533-4544.

SHGC-144070

MAPRE1

20q11.2

20

610 kB

RH57467

20q13.2
SHGC-80749

ZNF217570 kB

SHGC-83153* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

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L

Product Name

L

I

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Product code

N

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Color

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Content

Conc

I

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F

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S

H

Product Name

P

R

O

B

E

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(

I

Product code

Color

Content

V

D

Conc

SE 1 (1qh) Blue

KBI-20001B

Blue

10 test

5x

SE 15 (D15Z) Blue

KBI-20015B

Green

10 test

5x

SE 1 (1qh) Green

KBI-20001G

Green

10 test

5x

SE 15 (D15Z) Green

KBI-20015GBlue

10 test

5x

SE 1 (1qh) Red

KBI-20001R

Red

10 test

5x

SE 15 (D15Z) Red

KBI-20015R

Green

10 test

5x

SE 2 (D2Z) Blue

KBI-20002B

Blue

10 test

5x

SE 16 (D16Z2) Blue

KBI-20016B

Red

10 test

5x

SE 2 (D2Z) Green

KBI-20002G

Green

10 test

5x

SE 16 (D16Z2) Green

KBI-20016GBlue

10 test

5x

SE 2 (D2Z) Red

KBI-20002R

Red

10 test

5x

SE 16 (D16Z2) Red

KBI-20016R

Green

10 test5x

SE 3 (D3Z1) Blue

KBI-20003B

Blue

10 test5x

SE 17 (D17Z1) Blue

KBI-20017B

Red

10 test5x

SE 3 (D3Z1) Green

KBI-20003G

Green

10 test5x

SE 17 (D17Z1) Green

KBI-20017GBlue

10 test5x

SE 3 (D3Z1) Red

KBI-20003R

Red

10 test5x

SE 17 (D17Z1) Red

KBI-20017R

Green

10 test5x

SE 4 (D4Z1) Blue

KBI-20004B

Blue

10 test

5x

SE 18 (D18Z1) Blue

KBI-20018B

Red

10 test5x

SE 4 (D4Z1) Green

KBI-20004G

Green

10 test

5x

SE 18 (D18Z1) Green

KBI-20018GBlue

10 test5x

SE 4 (D4Z1) Red

KBI-20004R

Red

10 test

5x

SE 18 (D18Z1) Red

KBI-20018R

Green

10 test5x

SE 6 (D6Z1) Blue

KBI-20006B

Blue

10 test

5x

SE 20 (D20Z1) Blue

KBI-20020B

Red

10 test5x

SE 6 (D6Z1) Green

KBI-20006G

Green

10 test

5x

SE 20 (D20Z1) Green

KBI-20020GBlue

10 test5x

SE 6 (D6Z1) Red

KBI-20006R

Red

10 test

5x

SE 20 (D20Z1) Red

KBI-20020R

Green

10 test5x

SE 7 (D7Z1) Blue

KBI-20007B

Blue

10 test

5x

SE X (DXZ1) Blue

KBI-20023B

Red

10 test5x

SE 7 (D7Z1) Green

KBI-20007G

Green

10 test

5x

SE X (DXZ1) Green

KBI-20023GBlue

10 test5x

SE 7 (D7Z1) Red

KBI-20007R

Blue

10 test

5x

SE X (DXZ1) Red

KBI-20023R

Green

10 test5x

SE 8 (D8Z1) Blue

KBI-20008B

Green

10 test

5x

SE Y (DYZ3) Blue

KBI-20024B

Blue

10 test5x

SE 8 (D8Z1) Green

KBI-20008GRed

10 test

5x

SE Y (DYZ3) Green

KBI-20024G

Green

10 test5x

SE 8 (D8Z1) Red

KBI-20008R

Blue

10 test

5x

SE Y (DYZ3) Red

KBI-20024R

Red

10 test5x

SE 9 (classical) Blue

KBI-20009B

Green

10 test

5x

SE Y class. q arm Blue

KBI-20025B

Blue

10 test5x

SE 9 (classical) Green

KBI-20009GRed

10 test

5x

SE Y class. q arm Green

KBI-20025G

Green

10 test5x

SE 9 (classical) Red

KBI-20009R

Blue

10 test

5x

SE Y class. q arm Red

KBI-20025R

Red

10 test

5x

SE 10 (D10Z1) Blue

KBI-20010B

Green

10 test

5x

SE 1/5/19 Blue

KBI-20026B

Blue

10 test

5x

SE 10 (D10Z1) Green

KBI-20010G

Red

10 test

5x

SE 1/5/19 Green

KBI-20026GGreen

10 test

5x

SE 10 (D10Z1) Red

KBI-20010R

Blue

10 test

5x

SE 1/5/19 Red

KBI-20026R

Red

10 test5x

SE 11 (D11Z1) Blue

KBI-20011B

Green

10 test5x

SE 13/21 Blue

KBI-20027B

Blue

10 test5x

SE 11 (D11Z1) Green

KBI-20011GRed

10 test5x

SE 13/21 Green

KBI-20027GGreen

10 test5x

SE 11 (D11Z1) Red

KBI-20011R

Blue

10 test5x

SE 13/21 Red

KBI-20027RRed

10 test

5x

SE 12 (D12Z3) Blue

KBI-20012B

Green

10 test

5x

SE 14/22 Blue

KBI-20028B

Blue

10 test

5x

SE 12 (D12Z3) Green

KBI-20012GRed

10 test

5x

SE 14/22 Green

KBI-20028GGreen

10 test

5x

SE 12 (D12Z3) Red

KBI-20012R

Blue

10 test

5x

SE 14/22 Red

KBI-20028RRed

10 test5x* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

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O

L

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O

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B

E

S

(

I

V

D

)

Product Name

Product code

Color

Content

Conc

Product Name

Product code

Color

Content

Conc

Whole Chromosome 1 Blue

KBI-30001B

Blue

5 test5xWhole Chromosome 13 Blue

KBI-30013BBlue

5 test5xWhole Chromosome 1 Green

KBI-30001GGreen

5 test5xWhole Chromosome 13 Green

KBI-30013GGreen

5 test5xWhole Chromosome 1 Red

KBI-30001RRed

5 test5xWhole Chromosome 13 Red

KBI-30013RRed

5 test5xWhole Chromosome 2 Blue

KBI-30002BBlue

5 test5xWhole Chromosome 14 Blue

KBI-30014BBlue

5 test5xWhole Chromosome 2 Green

KBI-30002G

Green

5 test5xWhole Chromosome 14 Green

KBI-30014GGreen

5 test5xWhole Chromosome 2 Red

KBI-30002RRed

5 test5xWhole Chromosome 14 Red

KBI-30014RRed

5 test5xWhole Chromosome 3 Blue

KBI-30003BBlue

5 test5xWhole Chromosome 15 Blue

KBI-30015BBlue

5 test5xWhole Chromosome 3 Green

KBI-30003G

Green

5 test5xWhole Chromosome 15 Green

KBI-30015GGreen

5 test5xWhole Chromosome 3 Red

KBI-30003RRed

5 test5xWhole Chromosome 15 Red

KBI-30015RRed

5 test5xWhole Chromosome 4 Blue

KBI-30004BBlue

5 test5xWhole Chromosome 16 Blue

KBI-30016BBlue

5 test5xWhole Chromosome 4 Green

KBI-30004G

Green

5 test5xWhole Chromosome 16 Green

KBI-30016GGreen

5 test5xWhole Chromosome 4 Red

KBI-30004RRed

5 test5xWhole Chromosome 16 Red

KBI-30016RRed

5 test5xWhole Chromosome 5 Blue

KBI-30005B

Blue

5 test5xWhole Chromosome 17 Blue

KBI-30017BBlue

5 test5xWhole Chromosome 5 Green

KBI-30005G

Green

5 test5xWhole Chromosome 17 Green

KBI-30017GGreen

5 test5xWhole Chromosome 5 Red

KBI-30005RRed

5 test5xWhole Chromosome 17 Red

KBI-30017RRed

5 test5xWhole Chromosome 6 Blue

KBI-30006BBlue

5 test5xWhole Chromosome 18 Blue

KBI-30018BBlue

5 test5xWhole Chromosome 6 Green

KBI-30006GGreen

5 test5xWhole Chromosome 18 Green

KBI-30018GGreen

5 test5xWhole Chromosome 6 Red

KBI-30006RRed

5 test5xWhole Chromosome 18 Red

KBI-30018RRed

5 test5xWhole Chromosome 7 Blue

KBI-30007BBlue

5 test5xWhole Chromosome 19 Blue

KBI-30019BBlue

5 test5xWhole Chromosome 7 Green

KBI-30007GGreen

5 test5xWhole Chromosome 19 Green

KBI-30019GGreen

5 test5xWhole Chromosome 7 Red

KBI-30007RRed

5 test5xWhole Chromosome 19 Red

KBI-30019RRed

5 test5xWhole Chromosome 8 Blue

KBI-30008BBlue

5 test5xWhole Chromosome 20 Blue

KBI-30020B

Blue

5 test5xWhole Chromosome 8 Green

KBI-30008GGreen

5 test5xWhole Chromosome 20 Green

KBI-30020GGreen

5 test5xWhole Chromosome 8 Red

KBI-30008RRed

5 test5xWhole Chromosome 20 Red

KBI-30020RRed

5 test5xWhole Chromosome 9 Blue

KBI-30009BBlue

5 test5xWhole Chromosome 21 Blue

KBI-30021B

Blue

5 test5xWhole Chromosome 9 Green

KBI-30009G

Green

5 test5xWhole Chromosome 21 Green

KBI-30021GGreen

5 test5xWhole Chromosome 9 Red

KBI-30009RRed

5 test5xWhole Chromosome 21 Red

KBI-30021RRed

5 test5xWhole Chromosome 10 Blue

KBI-30010B

Blue

5 test5xWhole Chromosome 22 Blue

KBI-30022BBlue

5 test5xWhole Chromosome 10 Green

KBI-30010GGreen

5 test5xWhole Chromosome 22 Green

KBI-30022GGreen

5 test5xWhole Chromosome 10 Red

KBI-30010RRed

5 test5xWhole Chromosome 22 Red

KBI-30022RRed

5 test5xWhole Chromosome 11 Blue

KBI-30011BBlue

5 test5xWhole Chromosome X Blue

KBI-30023BBlue

5 test5xWhole Chromosome 11 Green

KBI-30011GGreen

5 test5xWhole Chromosome X Green

KBI-30023GGreen

5 test5xWhole Chromosome 11 Red

KBI-30011RRed

5 test5xWhole Chromosome X Red

KBI-30023RRed

5 test5xWhole Chromosome 12 Blue

KBI-30012BBlue

5 test5xWhole Chromosome Y Blue

KBI-30024BBlue

5 test5xWhole Chromosome 12 Green

KBI-30012GGreen

5 test5xWhole Chromosome Y Green

KBI-30024G

Green

5 test5xWhole Chromosome 12 Red

KBI-30012RRed

5 test5xWhole Chromosome Y Red

KBI-30024RRed

5 test5x* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

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Product code

Color

Content

Conc

Product Name

Product code

Color

Content

Conc

Sub Telomere 1pter Blue

KBI-40201BBlue

5 test5x

Sub Telomere 9pter Green

KBI-40217GGreen

5 test5x

Sub Telomere 1pter Green

KBI-40201GGreen

5 test5x

Sub Telomere 9pter Red

KBI-40217RRed

5 test5x

Sub Telomere 1pter Red

KBI-40201RRed

5 test5x

Sub Telomere 9qter Blue

KBI-40218B

Blue

5 test5x

Sub Telomere 1qter Blue

KBI-40202B

Blue

5 test5x

Sub Telomere 9qter Green

KBI-40218GGreen

5 test5x

Sub Telomere 1qter Green

KBI-40202GGreen

5 test5x

Sub Telomere 9qter Red

KBI-40218RRed

5 test5x

Sub Telomere 1qter Red

KBI-40202RRed

5 test5x

Sub Telomere 10pter Blue

KBI-40219BBlue

5 test5x

Sub Telomere 2pter Blue

KBI-40203BBlue

5 test5x

Sub Telomere 10pter Green

KBI-40219GGreen

5 test5x

Sub Telomere 2pter Green

KBI-40203G

Green

5 test5x

Sub Telomere 10pter Red

KBI-40219RRed

5 test5x

Sub Telomere 2pter Red

KBI-40203RRed

5 test5x

Sub Telomere 10qter Blue

KBI-40220B

Blue

5 test5x

Sub Telomere 2qter Blue

KBI-40204B

Blue

5 test5x

Sub Telomere 10qter Green

KBI-40220GGreen

5 test5x

Sub Telomere 2qter Green

KBI-40204GGreen

5 test5x

Sub Telomere 10qter Red

KBI-40220RRed

5 test5x

Sub Telomere 2qter Red

KBI-40204RRed

5 test5x

Sub Telomere 11pter Blue

KBI-40221B

Blue

5 test5x

Sub Telomere 3pter Blue

KBI-40205BBlue

5 test5x

Sub Telomere 11pter Green

KBI-40221GGreen

5 test5x

Sub Telomere 3pter Green

KBI-40205GGreen

5 test5x

Sub Telomere 11pter Red

KBI-40221RRed

5 test5x

Sub Telomere 3pter Red

KBI-40205RRed

5 test5x

Sub Telomere 11qter Blue

KBI-40222B

Blue

5 test5x

Sub Telomere 3qter Blue

KBI-40206BBlue

5 test5x

Sub Telomere 11qter Green

KBI-40222G

Green

5 test5x

Sub Telomere 3qter Green

KBI-40206GGreen

5 test5x

Sub Telomere 11qter Red

KBI-40222RRed

5 test5x

Sub Telomere 3qter Red

KBI-40206RRed

5 test5x

Sub Telomere 12pter Blue

KBI-40223B

Blue

5 test5x

Sub Telomere 4pter Blue

KBI-40207BBlue

5 test5x

Sub Telomere 12pter Green

KBI-40223GGreen

5 test5x

Sub Telomere 4pter Green

KBI-40207GGreen

5 test5x

Sub Telomere 12pter Red

KBI-40223RRed

5 test5x

Sub Telomere 4pter Red

KBI-40207RRed

5 test5x

Sub Telomere 12qter Blue

KBI-40224BBlue

5 test5x

Sub Telomere 4qter Blue

KBI-40208B

Blue

5 test5x

Sub Telomere 12qter Green

KBI-40224GGreen

5 test5x

Sub Telomere 4qter Green

KBI-40208GGreen

5 test5x

Sub Telomere 12qter Red

KBI-40224RRed

5 test5x

Sub Telomere 4qter Red

KBI-40208RRed

5 test5x

Sub Telomere 13qter Blue

KBI-40225BBlue

5 test5x

Sub Telomere 5pter Blue

KBI-40209BBlue

5 test5x

Sub Telomere 13qter Green

KBI-40225G

Green

5 test5x

Sub Telomere 5pter Green

KBI-40209G

Green

5 test5x

Sub Telomere 13qter Red

KBI-40225RRed

5 test5x

Sub Telomere 5pter Red

KBI-40209RRed

5 test5x

Sub Telomere 14qter Blue

KBI-40226BBlue

5 test5x

Sub Telomere 5qter Blue

KBI-40210B

Blue

5 test5x

Sub Telomere 14qter Green

KBI-40226GGreen

5 test5x

Sub Telomere 5qter Green

KBI-40210GGreen

5 test5x

Sub Telomere 14qter Red

KBI-40226RRed

5 test5x

Sub Telomere 5qter Red

KBI-40210RRed

5 test5x

Sub Telomere 15qter Blue

KBI-40227BBlue

5 test5x

Sub Telomere 6pter Blue

KBI-40211BBlue

5 test5x

Sub Telomere 15qter Green

KBI-40227GGreen

5 test5x

Sub Telomere 6pter Green

KBI-40211GGreen

5 test5x

Sub Telomere 15qter Red

KBI-40227RRed

5 test5x

Sub Telomere 6pter Red

KBI-40211RRed

5 test5x

Sub Telomere 16pter Blue

KBI-40228BBlue

5 test5x

Sub Telomere 6qter Blue

KBI-40212B

Blue

5 test5x

Sub Telomere 16pter Green

KBI-40228GGreen

5 test5x

Sub Telomere 6qter Green

KBI-40212GGreen

5 test5x

Sub Telomere 16pter Red

KBI-40228RRed

5 test5x

Sub Telomere 6qter Red

KBI-40212RRed

5 test5x

Sub Telomere 16qter Blue

KBI-40229BBlue

5 test5x

Sub Telomere 7pter Blue

KBI-40213BBlue

5 test5x

Sub Telomere 16qter Green

KBI-40229GGreen

5 test5x

Sub Telomere 7pter Green

KBI-40213GGreen

5 test5x

Sub Telomere 16qter Red

KBI-40229RRed

5 test5x

Sub Telomere 7pter Red

KBI-40213RRed

5 test5x

Sub Telomere 17pter Blue

KBI-40230BBlue

5 test5x

Sub Telomere 7qter Blue

KBI-40214B

Blue

5 test5x

Sub Telomere 17pter Green

KBI-40230GGreen

5 test5x

Sub Telomere 7qter Green

KBI-40214GGreen

5 test5x

Sub Telomere 17pter Red

KBI-40230RRed

5 test5x

Sub Telomere 7qter Red

KBI-40214RRed

5 test5x

Sub Telomere 17qter Blue

KBI-40231BBlue

5 test5x

Sub Telomere 8pter Blue

KBI-40215B

Blue

5 test5x

Sub Telomere 17qter Green

KBI-40231G

Green

5 test5x

Sub Telomere 8pter Green

KBI-40215GGreen

5 test5x

Sub Telomere 17qter Red

KBI-40231RRed

5 test5x

Sub Telomere 8pter Red

KBI-40215RRed

5 test5x

Sub Telomere 18pter Blue

KBI-40232B

Blue

5 test5x

Sub Telomere 8qter Blue

KBI-40216B

Blue

5 test5x

Sub Telomere 18pter Green

KBI-40232GGreen

5 test5x

Sub Telomere 8qter Green

KBI-40216GGreen

5 test5x

Sub Telomere 18pter Red

KBI-40232RRed

5 test5x

Sub Telomere 8qter Red

KBI-40216RRed

5 test5x

Sub Telomere 18qter Blue

KBI-40233B

Blue

5 test5x

Sub Telomere 9pter Blue

KBI-40217BBlue

5 test5x

Sub Telomere 18qter Green

KBI-40233GGreen

5 test5x* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

227

S

U

B

T

E

L

O

M

E

R

I

C

F

I

S

H

P

R

O

B

E

S

(

I

V

D

)

Product Name

Product code

Color

Content

Conc

Product Name

Product code

Color

Content

Conc

Sub Telomere 18qter Red

KBI-40233R

Red

5 test5x

Sub Telomere 21qter Blue

KBI-40238B

Blue

5 test5x

Sub Telomere 19pter Blue

KBI-40234B

Blue

5 test5x

Sub Telomere 21qter Green

KBI-40238GGreen

5 test5x

Sub Telomere 19pter Green

KBI-40234GGreen

5 test5x

Sub Telomere 21qter Red

KBI-40238RRed

5 test5x

Sub Telomere 19pter Red

KBI-40234RRed

5 test5x

Sub Telomere 22qter Blue

KBI-40239BBlue

5 test5x

Sub Telomere 19qter Blue

KBI-40235BBlue

5 test5x

Sub Telomere 22qter Green

KBI-40239GGreen

5 test5x

Sub Telomere 19qter Green

KBI-40235G

Green

5 test5x

Sub Telomere 22qter Red

KBI-40239RRed

5 test5x

Sub Telomere 19qter Red

KBI-40235RRed

5 test5x

Sub Telomere XYpter Blue

KBI-40240BBlue

5 test5x

Sub Telomere 20pter Blue

KBI-40236B

Blue

5 test5x

Sub Telomere XYpter Green

KBI-40240GGreen

5 test5x

Sub Telomere 20pter Green

KBI-40236GGreen

5 test5x

Sub Telomere XYpter Red

KBI-40240RRed

5 test5x

Sub Telomere 20pter Red

KBI-40236RRed

5 test5x

Sub Telomere XYqter Blue

KBI-40241BBlue

5 test5x

Sub Telomere 20qter Blue

KBI-40237BBlue

5 test5x

Sub Telomere XYqter Green

KBI-40241GGreen

5 test5x

Sub Telomere 20qter Green

KBI-40237GGreen

5 test5x

Sub Telomere XYqter Red

KBI-40241RRed

5 test5x

Sub Telomere 20qter Red

KBI-40237RRed

5 test5x* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

228

RUO PROBES
11Q23 / DLEU157............................................................................ 234

CTNND257....................................................................................... 252

15Q22 / 6Q2157.............................................................................. 234

DDIT3 BREAK57............................................................................... 253

15Q22 / 9Q3457.............................................................................. 235

DEK / NUP21457.............................................................................. 253

19Q13 / TP5357............................................................................... 235

DIC(9;20)57...................................................................................... 254

1Q21 / 8P2157................................................................................. 236

DIGEORGE II / SE 1057..................................................................... 254

1Q21 / SRD57.................................................................................. 236

DLEU1 / 13QTER57.......................................................................... 255

20Q-57............................................................................................. 237

DLEU1 / TP5357.............................................................................. 255

5Q DUAL-COLOR57.......................................................................... 237

EGFR / SE 757.................................................................................. 256

5Q- TRIPLE-COLOR57....................................................................... 238

ELN / 7Q2257.................................................................................. 256

6Q21 / MYC57.................................................................................. 238

ERBB2 / SE 1757.............................................................................. 257

6Q21 / SE 657.................................................................................. 239

ERCC1 / ZNF44357.......................................................................... 257

7Q-57............................................................................................... 239

ETV6 / RUNX157.............................................................................. 258

7Q- TRIPLE-COLOR57....................................................................... 240

ETV6 BREAK57................................................................................ 258

ALK / EML457.................................................................................. 240

EWSR1 / NFATC57........................................................................... 259

ALK BREAK57.................................................................................. 241

EWSR1 BREAK57............................................................................. 259

AR / SE X57...................................................................................... 241

FGFR1 BREAK57.............................................................................. 260

ATM / GLI157................................................................................... 242

FGFR2 / SE 1057.............................................................................. 260

ATM / SE 1157................................................................................. 242

FGFR3 / IGH57................................................................................. 261

AURKA57......................................................................................... 243

FGFR4 / 5Q11.257........................................................................... 261

AURKB57......................................................................................... 243

FIP1L1 / CHIC2 /PDGFRA DUAL-COLOR57....................................... 262

BCL2 / IGH57................................................................................... 244

FIP1L1 / CHIC2 /PDGFRA TRIPLE-COLOR57.................................... 262

BCL2 / IGH (TISSUE)57.................................................................... 244

FOXO1 BREAK57.............................................................................. 263

BCL2 BREAK57................................................................................ 245

FUS BREAK57.................................................................................. 263

BCL2 BREAK (TISSUE)57................................................................. 245

GATA4 / SE 857................................................................................ 264

BCL6 BREAK57................................................................................ 246

GLI1 / SE 1257................................................................................. 264

BCL6 BREAK (TISSUE)57................................................................. 246

HIRA / SHANK357............................................................................ 265

BCR / ABL157.................................................................................. 247

HUMAN CENTROMERE57................................................................ 265

BCR / ABL1 DC57............................................................................. 247

IGF1R / 15Q1157............................................................................. 266

BCR / ABL1 DC ES57........................................................................ 248

IGH BREAK57................................................................................... 266

BCR / ABL1 TC57............................................................................. 248

IGH BREAK (TISSUE)57.................................................................... 267

CBFB BREAK57................................................................................ 249

IRF4 / DUSP22 BREAK57................................................................. 267

CCND1 / IGH FUSION57................................................................... 249

JAK2 BREAK57................................................................................ 268

CCND1 /SE 1157.............................................................................. 250

KMT2A / AFF157............................................................................. 268

CCND1 BREAK57............................................................................. 250

KMT2A / MLLT157........................................................................... 269

CDK4 / SE 1257................................................................................ 251

KMT2A / MLLT357........................................................................... 269

CDKN2A / 9Q2157........................................................................... 251

KMT2A / MLLT457........................................................................... 270

CDKN2A / 9Q21 (TISSUE)57............................................................ 252

KMT2A / SE 1157............................................................................. 270

229

RUO PROBESKMT2A BREAK57............................................................................. 271

SNRPN / PML57............................................................................... 289

MAF/ IGH57..................................................................................... 271

SRD / SE 157.................................................................................... 290

MAFB /IGH57................................................................................... 272

SS18 BREAK57................................................................................ 290

MALT1 BREAK57.............................................................................. 272

STS / KAL1 / SE X57........................................................................ 291

MALT1 BREAK (TISSUE)57............................................................... 273

TBX1 / SHANK357........................................................................... 291

MDM2 / SE 1257.............................................................................. 273

TERC / 3Q1157................................................................................ 292

MDM4 / SE 157................................................................................ 274

TERC / MYC / SE 757....................................................................... 292

MECOM BREAK57............................................................................ 274

TERT / 5Q3157................................................................................. 293

MECOM BREAK TRIPLE-COLOR57.................................................... 275

TERT / 5Q31 (TISSUE)57.................................................................. 293

MECOM / RUNX157......................................................................... 275

TFE3 BREAK57................................................................................. 294

MET / SE 757................................................................................... 276

TMPRSS2-ERG57............................................................................. 294

MYC (8Q24) BREAK57...................................................................... 276

TOP2A / ERBB2 / SE 1757................................................................ 295

MYC (8Q24) BREAK (TISSUE)57....................................................... 277

TOP2A / SE 1757............................................................................. 295

MYC / SE 857................................................................................... 277

TP53 / ATM57.................................................................................. 296

MYC / IGH T(8;14) FUSION57........................................................... 278

TP53 / MPO57................................................................................. 296

MYCN / AFF357............................................................................... 278

TP53 / SE 1757................................................................................ 297

MYEOV / IGH57................................................................................ 279

TP53 / SE 17 (TISSUE)57................................................................. 297“N25” / SHANK357........................................................................... 279

UBE3A / PML57............................................................................... 298

NF1 / MPO57................................................................................... 280

WHSC1 / SE 457.............................................................................. 298

NSD1 / TERT57................................................................................ 280

XIST / SE X57................................................................................... 299

NUP98 BREAK57.............................................................................. 281

ZNF217 / 20Q1157.......................................................................... 299

PAFAH1B1 / 17P1157...................................................................... 281

MANUAL FISH PROBES (ASR).......................................................... 300

PDGFRB BREAK57........................................................................... 282

XL FISH PROBES (ASR).................................................................... 301

PML / RARA57................................................................................. 282

SATELLITE ENUMERATION FISH PROBES (ASR).............................. 302

PPARG BREAK57.............................................................................. 283

WHOLE CHROMOSOME FISH PROBES (ASR)................................... 303

PTEN / SE 1057............................................................................... 283

DNA PROBES (ASR).......................................................................... 303

RARA BREAK57................................................................................ 284

RNA PROBES (ASR).......................................................................... 303

RB1 / RCAN157................................................................................ 284

ACD RNA PROBES (RUO).................................................................. 303

RB1 / RCAN1, SE X/SE Y/ SE 1857................................................... 285

MANUAL ANCILLARIES (MOLECULAR)............................................ 304

RCAN1 / SE X / SE Y57..................................................................... 285

HUGO GENE CONVERSION TABLE................................................... 305

RET BREAK57.................................................................................. 286
ROS1 BREAK57................................................................................ 286
RUNX1 / RUNX1T157....................................................................... 287
SE 7 / SE 857................................................................................... 287
SE X / SE Y57................................................................................... 288
SE X / SE Y / SE 1857....................................................................... 288
SHOX / SE X57................................................................................. 289

230

A

D

V

A

N

C

E

D

S

T

A

I

N

I

11q23 / DLEU1

N

G

-

R

U

O

P

R

O

B

E

15q22 / 6q21
11q23 / DLEU1 13q14 probehybridized to MM patientmaterial showing a 13q14
deletion (1R2G).

15q22 / 6q21 hybridized to
MM patient material withgain of both critical regions
6q21 and 15q22.

Image kindly provided by
Prof. Jauch, Heidelberg.

Image kindly provided by
Prof. Jauch, Heidelberg.

11q23 / DLEU1 (13q14)

15q22 / 6q21

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10502

Green/Red

100 µL

RUO

KI-10504

Green/Red

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUND

Hybridization results delineated 11q23 and 11q25 as the most frequently gained
regions in Multiple Myeloma (MM) which supports a relevant pathogenetic role ofgenes in this region. Deletions of 13q14 are frequently detected by interphase FISH
in patients with newly diagnosed MM, correlate with increased proliferative activity,
and represent an independent adverse prognostic feature in MM.

Chromosome 6q amplifications encompassing 6q21-22 have been observed in
MM including the same region as in CLL. Amplification including band 15q22 hasbeen reported in MM. The 15q22 specific FISH probe is optimized to detect copy
numbers at 15q22.
The 6q21 specific DNA region is optimized to detect copy numbers at 6q21.

The 11q23 specific FISH probe is optimized to detect copy numbers at 11q23. The
DLEU1 (13q14) specific DNA region is optimized to detect copy numbers of the
DLEU1 (previously known as DLEU) gene region at 13q14.

REFERENCES
Cremer et al, 2005, Genes Chrom Cancer, 44; 194-203.

REFERENCES
Gonzalez et al, 2004, Haematologica, 89; 1213-1218.
Cremer et al, 2005, Genes Chrom Cancer, 44; 194-203.

UT5980

RH99154

SEC63

RB1
650 kB
SHGC-155029

TRIM13DLEU1560 kB

11

D11S2076

D6S24615

230 kB

D13S272

ZBTB16
11q23

SMAD6
SHGC-154519

6q21

D13S1477
13q14

15q22

275 kB6450 kB

13

D13S25* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

231

540 kB

S

A

D

V

A

N

C

E

D

S

T

A

I

N

I

15q22 / 9q34

N

G

-

R

U

O

P

R

O

B

E

19q13 / TP53
15q22 / 9q34 hybridized
to a normal interphase/
metaphase (2R2G).

19q13 / TP53 (17p13)
hybridized to patient material
showing a TP53 (17p13)
deletion (1R2G).

15q22 / 9q34

19q13 / TP53 (17p13)

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10508

Green/Red

100 µL

RUO

KI-10509

Green/Red

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUND

The hyperdiploid subtype in MM is defined by presence of multiple trisomic
chromosomes. Combination of the chromosome 9q34 and 15q22 specific regions
are important regions to detect the hyperdiploid subtype in MM which is usuallyassociated with a low frequency of IGH translocations.

TP53 (previously known as p53) gene deletion, which can be identified byinterphase FISH in almost a third of patients with newly diagnosed MM, is aprognostic factor predicting for short survival of MM patients treated withconventional-dose chemotherapy. Amplification of 19q13 has been reported ina variety of cancer. The 19q13 specific FISH probe is optimized to detect copy
numbers at 19q13.

The 15q22 and 9q34 FISH probe is designed as a dual-color assay to detect
amplifications at 15q22 and 9q34.

The TP53 (17p13) specific DNA region is optimized to detect copy numbers of the
TP53 gene region at 17p13.

REFERENCES
Cremer et al, 2005, Genes Chrom Cancer, 44; 194-203.

REFERENCES
Drach et al, 1998, Blood, 92; 802-809.
Cremer et al, 2005, Genes Chrom Cancer, 44; 194-203.

UT5980

SHGC-147754

15q22

SMAD6

17p13

540 kB

D17S960
RH55877

ASS1
430 kB

9q34

S

RH103512

SHGC-154519

CD37

335 kB15

19q13.3

TP53

D17S634

9

17

19

D19S1022* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

232

340 kB

A

D

V

A

N

C

E

D

S

T

A

I

N

I

1q21 / 8p21

N

G

-

R

U

O

P

R

O

B

E

S

1q21 / SRD
1q21 / 8p21 hybridized to anormal metaphase (2R2G).

1q21 / SRD (1p36)
hybridized to a normal
metaphase (2R2G).

1q21 / 8p21

1q21 / SRD (1p36)

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10503

Green/Red

100 µL

RUO

KI-10507

Green/Red

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUND

Amplifications of 1q21 are concurrent with dysregulated expression of MAF,
MMSET / FGFR3, or Deletion 13 and represent an independent unfavorable
prognostic factor. Allelic losses of the chromosome 8p21-22 have been reported
as a frequent event in several cancers.

Frequent loss of heterozygosity (LOH) on the short arm of chromosome 1 (1p)has been reported in a series of human malignancies. The combination with thepotentially amplified 1q21 region allows to detect deletions at 1p36 and gain of
1q21 in a single FISH assay.

The 1q21 specific FISH probe is optimized to detect copy numbers at 1q21. The
8p21 specific DNA region is optimized to detect copy numbers at 8p21.

The 1q21 specific FISH probe is optimized to detect copy numbers at 1q21. The
SRD 1p36 specific FISH probe is optimized to detect copy numbers of 1p at region
1p36 containing the markers D1S2795 and D1S253.

REFERENCESREFERENCES

Shaughnessy J., 2005, Hematology, 10 suppl, 1; 117-126.
Cremer et al, 2005, Genes Chrom Cancer, 44; 194-203.

Cremer et al, 2005, Genes Chrom Cancer, 44; 194-203.
Shaughnessy J., 2005, Hematology, 10 suppl, 1; 117-126.
D8S1066

8p21

PNOC

205 kB

1p36.3
SHGC-149299

SHGC-56649

530 kB
CHD5
SHGC-108153

RH64628

350 kB

1q21

8

S100A10

1q21

SHGC-144740

RH64628

350 kB
S100A10
SHGC-144740

1
1* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

233

A

D

V

A

N

C

E

D

S

T

A

I

N

I

20q-

N

G

-

R

U

O

P

R

O

B

E

S

5q Dual-Color
20q- (20q12) / 20q11 probehybridized to patient material
showing 20q- deletion(1R2G).

5q- (5q31; 5q33) probehybridized to patient material
showing a 5q33 deletion(1R2G).

Material kindly provided by
Labdia Labordiagnostik,
Vienna.

20q- (20q12) / 20q11

5q- (5q31; 5q33)

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10203

Green/Red

100 µL

RUO

KI-10209

Green/Red

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUND

Acquired deletions of the long arm of chromosome 20 are found in several
hematologic conditions and particularly in the myeloproliferative disorders (MPD)
and myelodysplastic syndromes and acute myeloid leukemia (MDS / AML). A
minimal critical region deleted in MPD and MDS has been identified at 20q12 which
includes a protein tyrosine phosphatase receptor gene.

The presence of del(5q), either as the sole karyotypic abnormality or as part ofa more complex karyotype, has distinct clinical implications for myelodysplastic
syndromes (MDS) and acute myeloid leukemia. Interstitial 5q deletions are themost frequent chromosomal abnormalities in MDS and are present in 10% to 15%
of MDS patients. Two different critical regions are described, one at 5q31-q33
containing the CSF1R and RPS14 gene regions, characteristic for the ‘5q-’
syndrome, and a more proximal located region at 5q13-q31 containing the CDC25C
and EGR1 gene regions.

The 20q- (20q12) specific FISH probe is optimized to detect copy numbers of
20q at region 20q12. A 20q11 region specific probe is included to facilitate
chromosome identification.

The 5q- specific FISH probe is optimized to detect copy numbers at the CDC25C/ EGR1 gene region at 5q31 and the CSF1R“/ RPS14 gene region at 5q33
simultaneously in a dual-color assay.

REFERENCES
Bench et al, 2000, Oncogene, 19; 3902-3913.
Asimakopoulos et al, 1994, Blood, 84; 3086-3094.

REFERENCES
Boultwood J e.a., Blood 2002, 99; 4638-4641.
Zhao N e.a., PNAS 1997, 94; 6948-6953.
Wang e.a., Haematologica 2008, 93; 994-1000.
Ebert BL e.a., Nature 2008, 451; 335-339.
Mohamedali A and Mufti GJ, Brit J Haematol 2008, 144; 157-168.

SHGC-144070

610 kB
MAPRE1
RH57467
20q11.2
20q12

20

STSG25365

PTPRT

370 kB

WI-2294

RH48032

CDC25C
EGR1

650 kB

SHGC-3896
5q31

5q33

D5S1907

CSF1R
RPS14

5

810 kB

D5S2014* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

234

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D

V

A

N

C

E

D

S

T

A

I

N

I

5q- Triple-Color

N

G

-

R

U

O

P

R

O

B

E

6q21 / MYC
5q- (5q31; 5q33) / TERT
(5p15)Triple-Color probehybridized to a normal
metaphase (2R2G2B).

6q21 / MYC (8q24)
CODE

COLOR

FORMATSTATUS

KI-10117

Green/Red

100 µLRUO

MENURESEARCH
BACKGROUND
Deletions affecting the long arm of chromosome 6 (6q) involving band 6q21
are among the most commonly observed chromosomal aberrations in lymphoidmalignancies and have been identified as adverse prognostic factor in subsets oftumors. Amplification of MYC (8q24) has been described in many types of solid
tumors, such as breast, cervical and colon cancers, as well as in myeloma, nonHodgkin’s lymphoma, gastric adenocarcinomas and ovarian cancer.

5q- (5q31; 5q33) / TERT (5p15) Triple-Color
CODE

COLOR

FORMATSTATUS

KI-10210

Green/Red/Blue

100 µLRUO

MENU

The 6q21 / MYC (8q24) FISH probe is designed as a dual-color assay to detect
deletions and amplifications at 6q21 and 8q24.

RESEARCH

REFERENCESBACKGROUND

Zhang, Y, 2000, Genes, Chrom. And Canc. 27; 52-58
Bentz, M et al, 1995, Blood, 85; 3610-3618

The 5q- specific FISH probe is optimized to detect copy numbers at the CDC25C/ EGR1 gene region at 5q31 and the CSF1R / RPS14 gene region at 5q33
simultaneously in a dual-color assay. The triple-color probe provides in addition to
the two critical regions a control in blue targeting the TERT (previously known as
hTERT) gene region at 5p15.

SEC63

Boultwood J e.a., Blood 2002, 99; 4638-4641.
Zhao N e.a., PNAS 1997, 94; 6948-6953.
Wang e.a., Haematologica 2008, 93; 994-1000.
Ebert BL e.a., Nature 2008, 451; 335-339.
Mohamedali A and Mufti GJ, Brit J Haematol 2008, 144; 157-168.
5p15.3

SHGC-140056

RH99154

REFERENCES

275 kB

MYC

6q21
D6S246

8q24.28

D8S1720

6

SHGC-154319

TERT

390 kB

D5S2269E

RH48032

CDC25C
EGR1

650 kB

SHGC-3896
5q31

5q33

D5S1907

CSF1R
RPS14

5

810 kB

D5S2014* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

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270 kB

S

A

D

V

A

N

C

E

D

S

T

A

I

N

I

6q21 / SE 6

N

G

-

R

U

O

P

R

O

B

E

S

7q6q21 / SE 6 probe hybridized
to a normal metaphase(2R2G).

7q- (7q22; 7q36) hybridized
to patient material showing a
7q36 deletion (1R2G).

Image kindly provided by
Prof. Jauch, Heidelberg.

6q21 / SE 6

7q- (7q22; 7q36)

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10105

Green/Red

100 µL

RUO

KI-10202

Green/Red

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUND

Deletions affecting the long arm of chromosome 6 (6q) are among the mostcommonly observed chromosomal aberrations in lymphoid malignancies and havebeen identified as an adverse prognostic factor in subsets of tumors including CLL.
A minimal deletion region has been identified within a 2-megabase segment of
6q21, between D6S447 and D6S246. The SEC63 gene is located within this criticalregion.

Loss of a whole chromosome 7 or a deletion of the long arm, del(7q), are recurring
abnormalities in malignant myeloid diseases. Most deletions are interstitial andthere are two distinct deleted segments of 7q. The majority of patients haveproximal breakpoints in bands q11-22 and distal breakpoints in q31-36. The CCAAT
displacement protein CUX1 gene region is located in the 7q22 critical region.
The 7q- specific FISH probe is optimized to detect copy number of 7q at 7q22 andat 7q36 simultaneously in a dual-color assay.

The 6q21 specific FISH probe is optimized to detect copy numbers of 6q at region
6q21.The chromosome 6 Satellite Enumeration FISH probe (SE 6) at D6Z1 isincluded to facilitate chromosome identification.

REFERENCES
LeBeau et al., 1996, Blood, 88; 1930-1935.
Doehner et al, 1998, Blood, 92; 4031-4035.

REFERENCES
Sherratt et al, 1997, Chromosome Res, 5; 118-124.
Zhang et al, 2000, Genes Chrom Cancer, 27; 52-58.

D7S2536

CUX1

D6Z1

RH99154

SEC63

7q22

520 kB

RH44454

275 kB
D7S2419

6q21

7q36

D6S246

7CUL1

330 kB

D7S2640

6* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

236

A

D

V

A

N

C

E

D

S

T

A

I

N

I

7q- Triple-Color

N

G

-

R

U

O

P

R

O

B

E

ALK / EML4
7q (7q22; 7q36) / SE 7
Triple-Color probe hybridized
to a normal metaphase(2R2G2B).

Hybridization of ALK EML4
fusion probe to a lungadenocarcinoma tissue
section showing normal
signal pattern (2R2G).

7q- (7q22; 7q36) / SE7 Triple-Color

ALK (2p23) / EML4 t(2;2) inv (2) Fusion

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10207

Green/Red/Blue

100 µL

RUO

KI-10746Green/Red

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUND

The 7q- specific FISH probe is optimized to detect copy number of 7q at
7q22 and at 7q36 simultaneously in a dual-color assay. The chromosome 7
Satellite Enumeration FISH probe (SE 7) at D7Z1 in blue is included to facilitate
chromosome identification.

The inversion in 2p21 and 2p23 leading to a fusion of the kinase domain of ALK(anaplastic lymphoma kinase) and EML4 (echinoderm microtubule associatedprotein like 4) has been described in 5-7% of non-small cell lung cancer (NSCLC)
cases.

REFERENCES

Multiple tyrosine kinsae inhibitors (TKI’s) specific for ALK have since been
approved for first line treatment of NSCLC-patients carrying the fusion gene ALKEML4. These ALK inhibitors include crizotinib (Xalkori), alectinib (Alecensa) andceritinib (Zykadia).

LeBeau et al., 1996, Blood, 88; 1930-1935.
Doehner et al, 1998, Blood, 92; 4031-4035.

The ALK / EML4 t(2;2); inv(2) Fusion probe is designed as a dual-color assay todetect the fusion of the ALK gene with the EML4 gene by paracentric inversion withbreakage and reunion occurring at bands 2p21 and 2p23.

D7S2536

D7Z1

CUX1

520 kBREFERENCES
7q22

RH44454

Soda et al, Nature, 2007, 448, 561-566.
Koivunen et al, Clin Cancer Res, 2008, 14, 4275-4283.

D7S2419
7q36

7

CUL1

S

330 kB

D7S2640

AFM347YA5

350 kB

2p23
SHGC-17159

ALK

Gap: 12 MB

2p21
SHGC-106023

350 kB
SHGC-104981

EML4

2

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

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A

D

V

A

N

C

E

D

S

T

A

I

N

I

ALK Break

N

G

-

R

U

O

P

R

O

B

E

S

AR / SE X
Hybridization of ALK
break probe to a lungadenocarcinoma tissue
section showing“positivetranslocation signal(1RG1R1G).

AR (Xq12) / SE X probehybridized to VCaP prostatecancer cell showing highlevel
AR gene amplification.

Image kindly provided by
Prof. Trapman, Erasmus
Medical Centre, Rotterdam.

ALK (2p23) BreakAR (Xq12) / SE X

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10747

Green/Red

100 µL

RUO

KI-10720

Green/Red

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUND

Translocations of the ALK (anaplastic lymphoma kinase) gene at 2p23 haveoriginally been associated with anaplastic lymphomas, B-cell lymphomas,
neuroblastomas and myofibroblastic tumors. At least 21 translocation partners
have been described, however 80% of the translocations involves the NPM1
gene (5q35). ALK rearrangements have been described in non-small cell lungcancer (NSCLC) cases. Multiple tyrosine kinsae inhibitors (TKI’s) specific for ALK
have since been approved for first line treatment of NSCLC-patients carrying thefusion gene ALK-EML4. These ALK inhibitors include“crizotinib (Xalkori), alectinib(Alecensa) and ceritinib (Zykadia).

The androgen receptor (AR) gene has been identified as a target gene for the
Xq12 amplification found in one-third of hormone-refractory prostate cancers. The
findings suggest that AR gene amplification and overexpression is involved in theemergence of prostate cancer.

The ALK (2p23) Break probe is optimized to detect translocations involving the
ALK gene region at 2p23.

Visakorpi T et al, 1995, Nat. Genet. 9; 401-406.
Koivisto P et al, 1997, Cancer Res. 57“; 314-319.

The AR (Xq12) FISH probe is optimized to detect copy numbers of the AR generegion at region Xq12. The chromosome X satellite enumeration probe (SE X) at
DXZ1 is included to facilitate chromosome identification.
REFERENCESREFERENCES
Soda et al, Nature, 2007, 448, 561-566.
Kwak et al, J Clin Oncol., 27(26):4247-53.
Koivunen et al, Clin Cancer Res, 2008, 14, 4275-4283.

DXZ1
Xq12

781E8LEAR
AFM347YA5

350 kB

2p23

340 kB

2684LE

SHGC-17159

X

SHGC-83664

ALK

340 kB

SHGC-144661

2* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

238

A

D

V

A

N

C

E

D

S

T

A

I

N

I

ATM / GLI1

N

G

-

R

U

O

P

R

O

B

E

S

ATM / SE 11
ATM (11q22) / GLI1 (12q13)
hybridized to a normal
metaphase (2R2G).

ATM (11q22) / SE 11
hybridized to patient material
showing a 11q22 deletion at
the ATM gene region (1R2G).

Image kindly provided by Dr.
Wenzel, Basel.

ATM (11q22) / GLI1 (12q13)

ATM (11q22) / SE 11

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10108

Green/Red

100 µL

RUO

KI-10103

Green/Red

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUND

Deletion of ATM at 11q22-q23 indicates a rather poor prognosis, amplificationof GLI1 (previously known as GLI) at 12q13 is associated with an intermediate
prognosis. The ATM (11q22) specific FISH probe is optimized to detect copy
numbers of the ATM gene region at 11q22.

Chromosome 11q22.3-23.1 deletions involving the ataxia-teleangiectasia mutated(ATM) locus are detected at diagnosis in 15-20% of cases of B-cell chronic
lymphocytic leukemia (CLL) and are associated with a relatively aggressive
disease. Loss of the 11q22-23 region, where the ataxia-telangiectasia mutated(ATM) gene is located, is also one of the most frequent secondary chromosomal
aberrations in mantle cell lymphoma.

The GLI1 (12q13) specific FISH probe is optimized to detect copy numbers of the
GLI1 gene region at 12q13.

The ATM (11q22.3) specific FISH probe is optimized to detect copy numbers of the
ATM gene region at region 11q22.3. The chromosome 11 Satellite Enumeration (SE11) at D11Z1 FISH probe is included to facilitate chromosome identification.

REFERENCES
Doehner H et al, 1997, Blood, 7; 2516-2522.
Boultwood J, 2001, J. Clin. Pathol., 54; 512-516.
Dierlamm J et al, 1998, Genes Chromosomes Cancer, 20; 155-166.
Doehner H at al, 1999, J. Molec. Med., 77; 266-281.

REFERENCES
Doehner et al, 1997, Blood, 89; 2516-2522.
Bigoni et al, 1997, Leukemia, 11; 1933-1940.

D12S1266
D11S4485

12q13

D11Z1

270 kB

D11S4485

GLI1
ATM
11q22

235 kB

RH75890

ATM

RH39918
11q22

11235 kB

RH39918

12
11* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

239

A

D

V

A

N

C

E

D

S

T

A

I

N

I

AURKA

N

G

-

R

U

O

P

R

O

B

E

S

AURKB
AURKA (20q13) / 20q11
probe hybridized tocolorectal carcinoma
material showing
amplification of AURKA,
gene region at 20q13.

AURKB (17p13) / SE 17
probe hybridized to tumor
tissue (2R2G).

Material kindly provided by
Dr. Carvalho, Amsterdam.

AURKA (20q13) / 20q11

AURKB (17p13) / SE 17

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10721

Green/Red

100 µL

RUO

KI-10722

Green/Red

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUND

Aurora kinase A (AURKA) gene amplification has been detected in approximately
12% of primary breast tumors, as well as in bladder, ovarian, colon, prostate,neuroblastoma and cervical cancer cell lines. The AURKA (20q13) / 20q11 probe isdesigned to detect copy numbers of the AURKA gene region at region 20q13.

Aurora kinase B (AURKB) localizes to microtubules, and is a key regulator of themitotic cell division and chromosome segregation processes. Gain of functionof AURKB correlates with cell proliferation, induction of multinuclear cells, andchromosomal instability.

The AURKA (20q13) FISH probe is optimized to detect copy numbers of the AURKA
gene region at region 20q13. The 20q11 specific DNA probe is included to facilitate
chromosome identification.

The significant interest of the gene in cancer diagnostics is related to thedriving function of AURKB in tumor progression, histological differentiation, andmetastasis. AURKB is predictive for the aggressive recurrence of many different
types of tumors, including hepatocellular carcinoma and oral squamous cell
carcinoma.

REFERENCES
Uchida et al, 2010, Cancer Genet Cytogenet 203; 324-327.
Sen et al, 2002, J of Nat Canc Inst 94; 1320-1329.
Lassmann et al, 2007, Clin Cancer Res 13; 4083-4091.

The AURKB (17p13) FISH probe is optimized to detect copy numbers of the AURKB
gene region at region 17p13. The Chromosome 17 Satellite Enumeration (SE 17)
probe at D17Z1 is included to facilitate chromosome identification.
REFERENCES

SHGC-144070

MAPRE1

20q11.2

20

Smith et al, 2005, Br J Cancer, 93; 719-729.

610 kB

RH57467

RH54968
17p13

20q13.2
SHGC-12066

AURKA

D17Z1
490 kB

AURKB

510 kB

RH36627

RH7569817* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

240

A

D

V

A

N

C

E

D

S

T

A

I

N

I

BCL2 / IGH

N

G

-

R

U

O

P

R

O

B

E

S

BCL2 / IGH (tissue)
BCL2 / IGH t(14;18) probehybridized to a normalinterphase/metaphase(2R2G).

BCL2 / IGH t(14;20) Fusion
Probe hybridized to paraffin
embedded lymph nodematerial (2R2G).

Image kindly provided by
P. May, Imperial College,
Hammersmith Hospital,
LondonBCL2 / IGH t(14;18) Fusion

BCL2 / IGH t(14;18) Fusion (tissue)

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10606

Green/Red

100 µL

RUO

KI-10755

Green/Red

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUND

The t(14;18) chromosomal translocation is a common cytogenetic abnormality inhuman lymphoma and is observed in about 85% of follicular lymphoma (FL) and up
to one-third of diffuse lymphomas (DL). Two breakpoint region clusters (brc) havebeen identified: a major breakpoint region (mbr) within the 3’ untranslated regionof the BCL2 proto-oncogene (approximately 60% of the cases) and a minor cluster
region (mcr) 30 kb 3’ of BCL2 ( approximately 25%).

Follicular lymphoma is a mature B-Cell lymphoma, characterized by the presenceof the t(14;18) translocation that juxtaposes the BCL2 locus on chromosome
18q21 to the immunoglobulin H (IGH) locus on chromosome 14q32, resulting in theoverexpression of the antiapoptotic protein BCL2.
The BCL2 / IGH t(14;18) Fusion probe is optimized to detect the reciprocaltranslocation t(14;18) in a dual-color, dual-fusion assay on formalin fixed paraffin
embedded tissue samples. In addition Kreatech has developed a probe for the
specific use on cell material (KBI-10606).

The BCL2 / IGH t(14;18)(q21;q32) specific FISH probe is optimized to detect thereciprocal translocation t(18;14), involving either of the two brc in the BCL2 genein a dual-color, dual-fusion assay. Kreatech has optimized this FISH probe for the
specific use on cell material (KBI-10606), or on tissue (KBI-10755).

REFERENCES
Taniwaki M et al, 1995, Blood, 86; 1481-1486.
Poetsch M et al, 1996, J Clin Oncol, 14; 963-969.

REFERENCES
Poetsch et al, 1996, J Clin Oncol, 14; 963-969.
Vaandrager et al, 2000, Genes Chrom Cancer, 27; 85-94.

RH75060
D14S683E

BCL2

RH75060
18q21

D14S683E

BCL2

IGH

1270 kB

18

18q21

IGH

1420 kB
SHGC-4651

14q32

1420 kB

18

14

SHGC-4651

RH6679014q32

14RH66790* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

2411270 kB

A

D

V

A

N

C

E

D

S

T

A

I

N

I

BCL2 Break

N

G

-

R

U

O

P

R

O

B

E

BCL2 Break (tissue)
BCL2 (18q21) Break probehybridized to a normal
metaphase.

BCL2 (18q21) Breakhybridized to paraffin
embedded tissue (2RG).

BCL2 (18q21) BreakBCL2 (18q21) Break (tissue)

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10612

Green/Red

100 µL

RUO

KI-10745

Green/Red

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUND

Follicular lymphoma is a mature B-cell lymphoma characterized by the presence ofthe t(14;18) translocation that juxtaposes the BCL2 locus on chromosome 18q21
to the immunoglobulin H (IGH) locus on chromosome 14q32, resulting in theoverexpression of the anti-apoptotic protein BCL2. Next to IGH, other translocation
partners to BCL2 are also known (e.g. IGK at 2p11.2 and IGL at 22q11). A breakor split assay is therefore best suited to detect rearrangements of the BCL2 generegion at 18q21.

Follicular lymphoma is a mature B-cell lymphoma characterized by the presenceof the t(14;18) translocation that juxtaposes the BCL2 locus on chromosome
18q21 to the immunoglobulin H (IGH) locus on chromosome 14q32, resulting in
the overexpression of the anti-apoptotic protein BCL2. Besides IGH, additionaltranslocation partners to BCL2 have been identified. A break or split assay istherefore best suited to detect rearrangements of the BCL2 gene region at 18q21.
The BCL2 (18q21) Break probe is optimized to detect translocations involving the
BCL2 gene region at 18q21 in a dual-color, split assay on paraffin embedded tissue
sections.

The BCL2 (18q21) Break FISH probe is optimized to detect translocations
involving the BCL2 gene region at 18q21 in a dual-color, split assay on metaphase/interphase spreads, bloodsmears and bone marrow cells.

Kreatech has developed this probe for the specific use on cell material (KBI10612), or on tissue (KBI-10745).

REFERENCES
Taniwaki M et al, 1995, Blood, 86; 1481-1486.
Poetsch M et al, 1996, J Clin Oncol, 14; 963- 969.
Einerson R et al, 2005, Am J Clin Pathol, 124; 421-429.

REFERENCES
Taniwaki M et al, 1995, Blood, 86; 1481-1486.
Poetsch M et al, 1996, J Clin Oncol, 14; 963- 969.
Einers R et al, 2005, Am J Clin Pathol, 124; 421-429.

RH75060

480 kB
D18S91
RH75060

BCL2
18q21

480 kB

D18S87540 kB

18S

D18S91BCL2

SHGC-4651

18q21

D18S87540 kB18

SHGC-4651* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

242

A

D

V

A

N

C

E

D

S

T

A

I

N

I

BCL6 Break

N

G

-

R

U

O

P

R

O

B

E

S

BCL6 Break (tissue)
BCL6 (3q27) Break probehybridized to patient material(1RG1R1G).

Hybridization of BCL6 breakprobe to a tissue section
showing“aberrant pattern(1RG1R1G).

Image kindly provided by
Prof. Siebert, Kiel.

BCL6 (3q27) BreakBCL6 (3q27) Break (tissue)

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10607

Green/Red

100 µL

RUO

KI-10730

Green/Red

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUND

Chromosomal translocations involving band 3q27 with various different partner
chromosomes represent a recurrent cytogenetic abnormality in B-cell nonHodgkin’s lymphoma. Kreatech has developed this probe for the specific use
on cell material (KBI-10607), or on tissue (KBI-10730). Two different breakpoint
regions have been identified; the major breakpoint region (MBR) is located within
the 5’ noncoding region of the BCL6 proto-oncogene, while the atypical breakpoint
region (ABR) is located approximately 200 kb distal to the BCL6 gene.

Chromosomal translocations involving band 3q27 with various different partner
chromosomes represent a recurrent cytogenetic abnormality in B-cell nonHodgkin’s lymphoma. Kreatech has developed this probe for the specific use on
cell material (KBI-10607), or on tissue (KBI-10730).
Two different breakpoint regions have been identified; the major breakpoint region(MBR) is located within the 5’ noncoding region of the BCL6 proto-oncogene, while
the atypical breakpoint region (ABR) is located approximately 200 kb distal to
the BCL6 gene. The BCL6 (3q27) Break probe is designed to flank both possible
breakpoints, thereby providing clear split signals.

The BCL6 (3q27) Break FISH probe is designed in a way to flank both possible
breakpoints, thereby providing clear split signals in either case.
REFERENCES

The BCL6 (3q27) Break probe is optimized to detect translocations involving the
BCL6 gene region at 3q27 in a dual-color, split assay on paraffin-embedded tissue
sections.

Butler et al, 2002, Cancer Res, 62; 4089-4094.
Sanchez-Izquierdo, 2001, Leukemia, 15; 1475-1484.

REFERENCES
Butler et al, 2002, Cancer Res, 62; 4089-4094.
Sanchez-Izquierdo, 2001, Leukemia, 15; 1475-1484.

D3S4060

540 kB
SHGC-143921

BCL6

MBR*
ABR*

SHGC-60245

3

D3S4060

410 kB

3q27

540 kB

SHGC-7226

SHGC-143921

BCL6

ABR* atypical breakpoint region
MBR* major breakpoint region

MBR*
ABR*

SHGC-60245

410 kB

3q27

3

SHGC-7226

ABR* atypical breakpoint region
MBR* major breakpoint region* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

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A

D

V

A

N

C

E

D

S

T

A

I

N

I

BCR / ABL1

N

G

-

R

U

O

P

R

O

B

E

S

BCR / ABL1 DC
BCR / ABL1 t(9;22) Fusion
probe hybridized on patientmaterial showing t(9;22)(q34;q11) reciprocaltranslocation (2RG1R1G).

BCR / ABL1 t(9;22),
Dual-Color, Single-Fusion
probe hybridized to patientmaterial showing t(9;22)translocation (1RG1R1G).

Image kindly provided by
Monika Conchon, São Paulo.

Material kindly provided by
Dr. Balogh, Budapest.

BCR / ABL1 t(9;22) Dual-Color, Single-Fusion

BCR / ABL1 t(9;22) Fusion
CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10005

Green/Red

100 µL

RUO

KI-10009

Green/Red

100 µL

RUO

KI-12005

Green/Red

200 µL

RUO

MENU
MENU

RESEARCHRESEARCH
BACKGROUNDBACKGROUND

A simple dual-color, single-fusion assay is preferably used for the initial screeningof CML and ALL patients. The Philadelphia chromosome, der(22q), is visualized
by a fusion signal while the der(9q) shows no signal. The BCR / ABL1 t(9;22) FISH
probe is optimized to detect the t(9;22)(q34;q11) reciprocal translocation in a dualcolor, single-fusion assay on metaphase/interphase spreads, blood smears andbone marrow cells.

The BCR / ABL1 t(9;22) Fusion FISH probe is optimized to detect the t(9;22)(q34;q11) reciprocal translocation in a dual-color, dual-fusion assay on metaphase/interphase spreads, blood smears and bone marrow cells.
This probe will also detect cryptic insertions of ABL1 (previously known as ABL)
into the BCR region not detectable by karyotyping and therefore described as Phnegative.

REFERENCES
Morris et al, 1990, Blood, 76; 1812-1818.
Dewald et al, 1998, Blood, 91; 3357-3365.
Kolomietz et al, 2001, Blood, 97; 3581-3588.
Huntly et al, 2003, Blood, 102; 1160-1168.
Tkachuk et al., 1990, Science, 250; 559-562.

REFERENCES
Morris et al, 1990, Blood, 76; 1812-1818.
Dewald et al, 1998, Blood, 91; 3357-3365.
Kolomietz et al, 2001, Blood, 97; 3581-3588.
Huntly et al, 2003, Blood, 102; 1160-1168.
Tkachuk et al., 1990, Science, 250; 559-562.

D22S940

IGLL5

ASS1
D22S940
SHGC-147754

ABL1

RH63154

IGLL5

ASS1

ABL1

BCR

NUP2141030 kB
9q34

22
NUP2149q34

9

D9S1991

RH27788BCR
620 kB

22q11.2

1050 kB

345 kB
22q11.2

22
IGLL1

D9S1991

9IGLL1
SHGC-107450* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

244

A

D

V

A

N

C

E

D

S

T

A

I

N

I

BCR / ABL1 DC ES

N

G

-

R

U

O

P

R

O

B

E

S

BCR / ABL1 TC
BCR / ABL1 t(9;22),
Dual-Color, Single-Fusion
probe hybridized to patientmaterial showing t(9;22)translocation (1RG1R1G).

BCR / ABL1 t(9;22),TripleColor, Dual Fusion
probe hybridized on
patient material showing
translocation of distal BCR(1BG1RB1R1G).

Material kindly provided by
Dr. Balogh, Budapest.

Image kindly provided by
Prof. Siebert, Kiel.

BCR / ABL1 t(9;22) Dual-Color, Single-Fusion, Extra Signal

BCR / ABL1 t(9;22) Triple-Color, Dual-Fusion

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10008

Green/Red

100 µL

RUO

KI-10006

Green/Red/Blue

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUND

A simple dual-color, single-fusion assay is preferably used for the initial screeningof CML and ALL patients. The Philadelphia chromosome, der(22q), is visualized
by a fusion signal while the der(9q) shows no signal. The BCR / ABL1 t(9;22) FISH
probe is optimized to detect the t(9;22)(q34;q11) reciprocal translocation in a dualcolor, single-fusion, extra-signal assay on metaphase/interphase spreads, bloodsmears and bone marrow cells.

The BCR / ABL1 t(9;22) FISH probe is a triple-color, dual-fusion probe built fromthe same regions as the dual-color, dual-fusion probe, but the proximal BCR regionis labeled in blue. Using the triple-color probe allows to distinguish between thederivative chromosome 22, the Philadelphia chromosome, which will be observed
as purple (red/blue) color, while the derivative chromosome 9 will show a yellow(red/green) signal.

REFERENCESREFERENCES

Morris et al, 1990, Blood, 76; 1812-1818.
Dewald et al, 1998, Blood, 91; 3357-3365.
Kolomietz et al, 2001, Blood, 97; 3581-3588.
Huntly et al, 2003, Blood, 102; 1160-1168.
Tkachuk et al., 1990, Science, 250; 559-562.

Morris et al, 1990, Blood, 76; 1812-1818.
Dewald et al, 1998, Blood, 91; 3357-3365.
Kolomietz et al, 2001, Blood, 97; 3581-3588.
Huntly et al, 2003, Blood, 102; 1160-1168.
Tkachuk et al., 1990, Science, 250; 559-562.

SHGC-147754

IGLL5

ASS1
ABL1

D22S940

D22S940

SHGC-147754

22q11.2
SHGC-107331

1050 kB

ABL1

BCR

22
NUP214
9q34

IGLL5

ASS1

425 kB345 kB
22q11.2

1050 kB

BCR

22
NUP214

IGLL1
9q34

D9S1991

99

D9S1991

RH27788

SHGC-170333

IGLL1
SHGC-107450* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

245

535 kB

A

D

V

A

N

C

E

D

S

T

A

I

N

I

CBFB Break

N

G

-

R

U

O

P

R

O

B

E

CCND1 / IGH Fusion
Hybridization of CBFB
break probe to a metaphasespread showing normal
pattern (2RG).

CCND1 / IGH t(11;14) Fusion
probe hybridized to a normalinterphase/metaphase(2R2G).

CBFB t(16;16), inv(16) BreakCCND1 / IGH t(11;14) Fusion

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10304

Green/Red

100 µL

RUO

KI-10604

Green/Red

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUND

Inv(16)(p13;q22) and t(16;16)(p13;q22) are recurring chromosomal rearrangements
in AML. In both the inversion and translocation, the critical genetic event is thefusion of the CBFB gene at 16q22 to the smooth muscle myosin heavy chain(MYH11) at 16p13. A deletion of between 150 and 350 kb centromeric to the p-arm
inversion breakpoint cluster region can be observed in some patients containing
the 5’ portion of the myosin heavy chain (MYH11) gene.

Mantle cell lymphoma is a subtype of non-Hodgkin lymphoma characterized
by poor prognosis. Cytogenetically t(11;14) is associated with 75% of mantle
cells lymphomas. The translocation breakpoints are scattered within the 120 kb
region adjacent to CCND1 (previously known as BCL1). The translocation leads
to overexpression of cyclin D1 due to juxtaposition of the Ig heavy chain geneenhancer on 14q32 to the cyclin D1 gene on 11q13.

The CBFB t(16;16) inv(16) break FISH probe is optimized to detect the inversionof chromosome 16 involving the CBFB gene region at 16q22 in a dual-color, split
assay.

The CCND1 / IGH t(11;14)(q13;q32) specific FISH probe is optimized to detect thereciprocal translocation t(11;14) in a dual-color, dual-fusion assay.
REFERENCESREFERENCES

Vaandrager et al, 1996, Blood, 88; 1177-1182.

Dauwerse et al, 1993, Hum.Mol.Genet., 2; 1527-1534.
Marlton et al, 1995, Blood, 85; 772-779.

RH52377
D14S683E

MYEOV
RH113713

275 kB

11q13

RH54691

CBFB

16

CCND1
FGF4
FGF3

D16S2846

335 kB

16q22

S

RH48109

RH32600

IGH

1200 kB
14q32

14

RH6679011* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

246

1420 kB

A

D

V

A

N

C

E

D

S

T

A

I

N

I

CCND1 /SE 11

N

G

-

R

U

O

P

R

O

B

E

CCND1 BreakCCDN1 (11q13) / SE 11
probe hybridized to patientinterphases / metaphaseshowing CCDN1 (11q13)
amplification with polyploidy
for chromosome 11.

CCND1 (11q13) Break probehybridized to a normal
metaphase (2R2G).

CCND1 (11q13) / SE 11

CCND1 (11q13) Break

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10734

Green/Red

100 µL

RUO

KI-10609

Green/Red

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUND

The binding of cyclin D1 (also named CCND1 or BCL1) to cyclin-dependent
kinases (CDKs) leads to the phosphorylation of retinoblastoma protein (pRb),
subsequently triggering the release of E2F transcription factors to allow G1 to S
phase progression of the cell cycle. Consistent with this function, overexpressionof cyclin D1 results in a more rapid progression from the G1 to S phase transition
and in a reduced serum dependency in fibroblast cells, characteristics typicallyseen in cancer cells. The CCND1 (11q13) FISH probe is optimized to detect
copy numbers of the CCND1 gene region at region 11q13. The Chromosome 11
Satellite Enumeration (SE 11) probe at D11Z1 is included to facilitate chromosome
identification.

Overexpression of the Cyclin D1 gene caused by amplification or translocation
is described for several types of cancer. A t(11;14) is the main characteristic
aberration in mantle cell lymphoma (documented in 40-70% of the cases. In MM,
the same translocation t(11;14)(q13:q32) is the most common, with a reported
frequency of 15% to 20% of the cases.
Kreatech has developed this probe to detect rearrangements of the CCND1
gene region at 11q13 (KBI-10609) or for the translocation t(11;14) in Mantle Cell
Lymphoma (KBI-10604) and for MM (KBI-10605). The CCND1 (11q13) Break FISH
probe is optimized to detect translocations involving the CCND1 gene region at
11q13 in a dual-color, split assay on metaphase/interphase spreads.

REFERENCESREFERENCES

Okami et al, 1999, Oncogene 18; 3541-3645.
Freier et al, 2003, Cancer Res; 1179-1182.

Vaandrager et al, 1996, Blood, 88; 1177-1182.
Vaandrager et al, Blood, 89; 349-350.

RH102068

510 kB

D11Z1
RH103547
11q13

RH103450

MYEOV

CCND1
11q13

530 kB

11

CCND1

RH67810

FGF4
FGF3

SHGC-147246

550 kB

SHGC-144332

11* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

247

S

A

D

V

A

N

C

E

D

S

T

A

I

N

I

CDK4 / SE 12

N

G

-

R

U

O

P

R

O

B

E

CDKN2A / 9q21
CDK4 (12q13) / SE 12 probehybridized to liposarcoma
tissue showing multiple
amplification involving the
CDK4 gene region at 12q13(3+R2G).

CDKN2A (9p21) / 9q21
hybridized to a metaphasespread showing a normal
pattern (2R2G).

Image kindly provided by Dr.
Sapi, Hungary.

CDK4 (12q13) / SE 12

CDKN2A (9p21) / 9q21

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10725

Green/Red

100 µL

RUO

KI-10402

Green/Red

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUND

Amplification of the CDK4 gene region at 12q13-q15 has been observed in several
types of cancer, especially in gliomas and sarcomas. CDK4 codes for a cyclin
dependent kinase which is involved in controlling progression through the G1
phase of the cell cycle. The oncogenic potential of CDK4 activation has been
related to the deregulation of the G1 phase by increasing the hyperphosphorylationof retinoblastoma tumor suppressor protein helping to cancel its growth-inhibitory
effects.

Hemizygous deletions and rearrangements of chromosome 9, band p21 areamong the most frequent cytogenetic abnormalities detected in pediatric acutelymphoblastic leukemia (ALL). This deletion includes loss of the CDKN2A(previously known as p16, INK4A or MTS1) / CDKN2B (previously known as p15,
INK4B or MTS2) genes, which are cell cycle kinase inhibitors and important inleukemogenesis.
The CDKN2A (9p21) specific FISH probe is optimized to detect copy numbers of
the CDKN2A gene region at region 9p21. The 9q21 region probe is included tofacilitate chromosome identification.

The CDK4 (12q13) FISH probe is optimized to detect copy numbers of the CDK4
gene region at 12q13. The chromosome 12 satellite enumeration probe (SE 12) at
D12Z3 is included to facilitate chromosome identification.

REFERENCESREFERENCES

Dreyling et al, 1995, Blood, 86; 1931-1938.
Southgate et al, 1995, Br J Cancer, 72; 1214-1218.

Kuhnen et al, 2002, Virchows Arch 441“; 299-302.
Shimada et al, 2006, Hum Path 37(9)“; 1123-1129.

D9S1749

CDKN2A
(p16)
D12Z3

9p21
D12S1266

350 kBCDKN2B(p15)
D9S975

12q13

CDK4

900 kB
9q21

D12S1529

RH40366

440 kB
PIP5K1B

12

SHGC-82248

9* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

248

S

A

D

V

A

N

C

E

D

S

T

A

I

N

I

CDKN2A / 9q21 (tissue)

N

G

-

R

U

O

P

R

O

B

E

CTNND2
CDKN2A (9p21) / 9q21
(tissue) probe hybridized totissue (2R2G).

Cri-Du-Chat CTNND2 (5p15)/ 5q31 probe hybridized to anormal metaphase (2RG).

CDKN2A (9p21) / 9q21 (tissue)

CTNND2 (5p15) / 5q31

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10710

Green/Red

100 µL

RUO

KI-40106

Green/Red

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUND

Homozygous and hemizygous deletions of 9p21 are the earliest and most common
genetic alteration in bladder cancer. The CDKN2A (INK4A) gene has been identified
as tumor suppressor gene in this region which is commonly deleted in bladdercancer. The loss of DNA sequences on chromosomal bands 9p21-22 has been
documented also in a variety of malignancies including leukemias, gliomas, lungcancers, and melanomas. The CDKN2A (9p21) FISH probe is optimized to detect
copy numbers of the CDKN2A gene region at region 9p21. The 9q21 region probe isincluded to facilitate chromosome identification.

Cri-Du-Chat syndrome is an autosomal deletion syndrome caused by a partial
deletion of chromosome 5p. It is characterized by a distinctive, high-pitched,catlike cry in infancy with growth failure, microcephaly, facial abnormalities, andmental retardation throughout life. Loss of a small region in band 5p15.2 (Cri-DuChat critical region) correlates with all the clinical features of the syndrome withthe exception of the catlike cry, which maps to band 5p15.3 (catlike cry criticalregion).
The Cri-Du-Chat region probe is optimized to detect copy numbers at the CTNND2
gene region in the Cri-Du-Chat critical region at 5p15.2. The 5q31 specific FISH
probe is included as control probe.

REFERENCES
Stadler et al, 1994, Cancer Res, 54:2260-2063.
Williams et al, 1995, Hum Mol Genet; 4: 1569-1577.

REFERENCES
Overhauser et al, 1994, Hum. Mol. Genet., 3; 247-252.
Gersh et al, 1997, Cytogenet Cell Genet., 77; 246-251.

D9S1749

CDKN2A(p16)
9p21

350 kBCDKN2B(p15)
D9S975

SHGC-107760
5p15.2CTNND2

9q21

RH40366

570 kB

440 kB
D5S2874

PIP5K1B
SHGC-82248

9

RH48032

CDC25C
650 kB

5q31

EGR1
SHGC-3896

5* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

249

S

A

D

V

A

N

C

E

D

S

T

A

I

N

I

DDIT3 Break

N

G

-

R

U

O

P

R

O

B

E

S

DEK / NUP214
DDIT3 (12q13) Break probehybridized to a normal
metaphase (2RG).

Hybridization of DEK/
NUP214 Fusion Probe to a
positive cell line showing afusion due to t(6;9).

DDIT3 (12q13) BreakDEK / NUP214 t(6;9) Fusion

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10714

Green/Red

100 µL

RUO

KI-10306

Green/Red

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUND

Liposarcoma is one of the most frequent sarcomas in adults, representing 10
to 16 percent of soft tissue sarcomas. Most patients with round cell / myxoid
liposarcoma have an acquired t(12;16)(DDIT3-FUS) or t(12;22)(DDIT3-EWS)
translocation, both of which involve the DDIT3 gene at 12q13. A break or split
probe for DDIT3 is best used to analyze translocation of the DDIT3 (12q13) gene onformalin fixed paraffin embedded tissue for routine clinical diagnosis.

The chromosomal translocation t(6;9) (p22;q34) is associated with a specificsubtype of acute myeloid leukemia (AML) and constitutes 0.5% to 4% of all AML
cases. The translocation results in a fusion between the DEK oncogene (6p22)
and the nucleoporin 214 kDa (NUP214 at 9q34; previously known as CAN). The
exact mechanism by which the fusion protein DEK-NUP214 contributes to leukemia
development has not been identified. Patients with t(6;9) AML have a very poor
prognosis.

The DDIT3 (12q13) Break probe is optimized to detect translocations involving the
DDIT3 gene region at 12q13 in a dual-color, break assay.

The DEK / NUP214 t(6;9) specific FISH probe has been optimized to detect thereciprocal translocation t(6;9) in a dual-color, dual-fusion assay on metaphase/interphase spreads, blood smears and bone marrow cells.

REFERENCES
Panagopoulos et al, 1994, Cancer Res, 54; 6500-6503.
Schoenmakers et al, 1994, Genomics, 20; 210-222.

REFERENCES
Von Lindern et al, 1992, Mol. Cell. Biol.,12; 1687-1697.
Ageberg et al, 2008, Gen. Chrom. Canc., 47; 276-287.
Chi et al, 2008, Arch. Pathol. Lab. Med., 132; 1835-1837.

RH75353

700 kB
RH48794
12q13

RH102047

DDIT3

6p22

RH44152

680 kB

DEK

RH118682

D9S1201320 kB

ABL1

12

NUP214(CAN)

SHGC-79367

9q34

9

SHGC-148792

6* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

250

1030 kB

A

D

V

A

N

C

E

D

S

T

A

I

N

I

dic(9;20)

N

G

-

R

U

O

P

R

O

B

E

S

DiGeorge II / SE 10
dic(9;20) Triple-Color.

DiGeorge II(10p14) / SE 10
probe hybridized to DiGeorge
II patient material showing adeletion of the DGSII region
at 10p14 (1R2G).

Image kindly provided byAzzedine Aboura, Hôpital
Robert Debré Paris.

Image kindly provided by Dr.
Ann Nordgren, Stockholm.

dic(9;20) Triple-Color

DiGeorge II (10p14) / SE 10

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10405

Green/Red/Blue

100 µL

RUO

KI-40105

Green/Red

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUND

The dic(9;20)(p13.2;q11.2) is a recurrent chromosomal abnormality in pediatric
Bcell precursor acute lymphoblastic leukemia (BCP-ALL), which occurs in ~2%of the cases. It is associated with an intermediate outcome with relapses being
relatively frequent, compared to other common cytogenetic subgroups of BCP-ALL(e.g. high hyperploidy and t(12;21)). The dic(9;20) is an unbalanced rearrangement
involving chromosomes 9 and 20, resulting in the co-localisation of the respective
centromeres and concomitant loss of the chromosome arms 9p and 20q.

DiGeorge and VCFS present many clinical problems and are frequently associatedwith deletions within 22q11.2, but a number of cases have no detectable molecular
defect of this region. A number of single case reports with deletions of 10p
suggest genetic heterogeneity of DiGeorge syndrome. FISH analysis demonstrates
that these patients have overlapping deletions at the 10p13 / 10p14 boundary.
The shortest region of deletion overlap (SRO) has been identified in a 1 cM interval
including makers D10S547 and D10S585.

The dic(9;20) Triple-Color FISH probe is optimized to detect the dicentric (9;20)(p13.2;q11.2) in a triple-color assay on metaphase/interphase spreads, bloodsmears and bone marrow cells.

The DiGeorge II region probe is optimized to detect copy numbers of the DGSII at
10p14. The chromosome 10 satellite enumeration (SE 10) FISH probe at D10Z1 isincluded to facilitate chromosome identification.

REFERENCESREFERENCES

Forestier et al., Genes Chromosome Cancer, 2008, 47; 149-158.
Pichler H et al., Br J Haematol, 2010, 149; 93-100.
Schmiegelow K et al., Leukemia, 2010, 24; 345-54.
Zachariadis V et al., Leukemia, 2011, 25; 22-628.
Zachariadis V et al., Br J Haematol, 2012, 159; 488-491.

Monaco et al, 1991, Am. J. Med. Genet., 39; 215-216.
Schuffenhauer et al, 1998, Eur. J. Hum. Genet., 6; 213-225.

10p14

SHGC-82096
DGSII

350 KB

D10Z1
RH12467

RH66174

360 kB

D9Z1

20p11.2
RH9264710
20

20q11.2
RH428099
330 kB
D20S494* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

251

A

D

V

A

N

C

E

D

S

T

A

I

N

I

DLEU1 / 13qter

N

G

-

R

U

O

P

R

O

B

E

S

DLEU1 / TP53
DLEU1 (13q14) / 13qter
probe hybridized to patientmaterial showing a 13q14
deletion (1R2G).

DLEU1 (13q14) / TP53(17p13) hybridized to anormal metaphase (2R2G).

Image kindly provided by Dr.
Dastugue, Toulouse.

DLEU1 (13q14) / 13qter

DLEU1 (13q14) / TP53 (17p13)

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10102

Green/Red

100 µL

RUO

KI-10113

Green/Red

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUND

Deletions of chromosome 13q14 have been reported not only in CLL but in a varietyof human tumors, including other types of lymphoid and myeloid tumors, as wellas prostate, head and neck, and non-small cell lung cancers. The deletion of 13q
may be limited to a single locus (13q14), or accompanied with the loss of a larger
interstitial region of the long arm of chromosome 13. A minimal critical region of
400 kb has been described containing the DLEU1, DLEU2 and RFP2 genes.

Deletion of DLEU1 (previously known as DLEU) at 13q14 indicates a rather good
prognosis, deletion of TP53 (previously known as p53) at 17p13 is associated withpoor prognosis. The DLEU1 (13q14) specific FISH probe is optimized to detect
copy numbers at the DLEU1 gene region at 13q14. The TP53 (17p13) specific FISH
probe is optimized to detect copy numbers of the TP53 gene region at 17p13
REFERENCES

The DLEU1 (13q14) specific FISH probe is optimized to detect copy numbers of
the DLEU1 (previously known as DLEU) gene region at 13q14. The 13qter (13q34)
region is included to facilitate chromosome identification.

Amiel A et al, 1997, Cancer Gener.Cytogenet, 97; 97-100.
Drach J et al, 1998, Blood, 92; 802-809.
Stilgenbauer S et al, 1998, Oncogene, 16; 1891 - 1897.
Wolf S et al, 2001, Hum. Molec. Genet., 10; 1275-1285.

REFERENCES
Wolf et al, 2001, Hum Mol Genet, 10; 1275-1285.
Corcoran et al, 1998, Blood, 91; 1382-1390.

17p13

RB1

D17S960

650 kB335 kB

D13S1477

RB1

13q14

650 kB

DLEU1

D13S1477

TRIM13
DLEU1
D13S25TP53

230 kB

D13S272

230 kB

D17S63417
450 kB

D13S272
13q14

TRIM1313

450 kB

D13S25

RH45055

TFDP1
GAS6
13q34

13

1000 kB

RASA3
RH17923* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

252

A

D

V

A

N

C

E

D

S

T

A

I

N

I

EGFR / SE 7

N

G

-

R

U

O

P

R

O

B

E

S

ELN / 7q22
EGFR (7p11) / SE 7
hybridized to colon tissue(2R2G).

Williams-Beuren ELN (7q11)/ 7q22 probe hybridized to anormal metaphase (2RG).

EGFR (7p11) / SE 7

ELN (7q11) / 7q22

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10702

Green/Red

100 µL

RUO

KI-40111

Green/Red

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUND

Epidermal growth factor receptor (EGFR) is a cell membrane protein, providing
signal transduction and cell growth. It is a member of the Erb-B family of type I
receptor tyrosine kinases and implicated in the development and progression of
non-small cell lung carcinomas (NSCLC), breast, intestine, and other organs. EGFR
has been found to act as a strong prognostic indicator in head and neck, ovarian,cervical, bladder and oesophageal cancers. In these cancers, increased EGFR
expression was associated with reduced recurrence-free or overall survival.

Williams-Beuren syndrome (WS) is characterized by cardiovascular disease,distinctive facial features, connective tissue abnormalities, mental retardation andendocrine abnormalities. Over 99% of individuals with the clinical diagnosis of
WS have this contiguous gene deletion, that encompasses the elastin (ELN) generegion including ELN, LIMK1, and the D7S613 locus.
The Williams-Beuren region probe is optimized to detect copy numbers of the ELN
gene region at 7q11. The 7q22 region specific FISH probe at 7q22 is included ascontrol probe.

The EGFR (7p11) FISH probe is optimized to detect copy numbers of the EGFR
gene region at region 7p11. The chromosome 7 satellite enumeration (SE 7) probeat D7Z1 is included to facilitate chromosome identification.

REFERENCES
Ewart, et al, 1993, Nat. Genet., 5; 11-16.
Botta et al, 1999, J. Med. Genet., 36; 478-480.

REFERENCES
Wang et al, 1993, Jpn J Hum Genet, 38: 399-406.
Nicholoset al, 2001, Eur J Cancer, 37: 9-15.

SWSS2677

ELN
LIMK1

RH105858

7p11.2

D7Z1

EGFR

340 kB

415 kB

CLIP2
7q11.2

D7S2357

BV005603

7q22
AFM353TC97CUX1

520 kB

7
RH44454* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
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253

A

D

V

A

N

C

E

D

S

T

A

I

N

I

ERBB2 / SE 17

N

G

-

R

U

O

P

R

O

B

E

S

ERCC1 / ZNF443
ERBB2 (17q12) / SE 17 probehybridized to breast tumor
tissue showing amplificationof ERBB2 / SE 17.

ERCC1 (19q13) / ZNF443(19p13) probe hybridized toparaffin embedded tissue(2R2G).

ERCC1 (19q13) / ZNF443 (19p13)

ERBB2 (17q12) / SE 17
CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10701

Green/Red

100 µL

RUO

KI-10739

Green/Red

100 µL

RUO

KI-14701

Green/Red

500 µL

RUO

MENU
MENU

RESEARCHRESEARCH
BACKGROUNDBACKGROUND

Excision repair cross-complementing rodent repair deficiency, complementationgroup 1 (ERCC1) is a critical gene in the Nucleotide excision repair pathway.
A growing list of reports links cisplatin, carboplatin, and oxaliplatin based
chemotherapy resistance to ERCC1 expression levels in several tumors. ERCC1
has been shown to be an important marker to predict responsiveness to cisplatinbased chemotherapy. Low ERCC1 gene expression correlates with prolonged
survival after cisplatin-based chemotherapy.

The ERBB2 (or HER2) gene encodes a receptor tyrosine kinase involved in growth
factor signaling. Overexpression of this gene is seen in about 20% of invasive
breast cancers. ERBB2 gene amplification is a permanent genetic change that
results in this continuous overexpression of ERBB2. Trastuzumab (commonly
known as Herceptin) has been developed to be effective against ERBB2-positive
breast cancer. ERBB2 amplification is also observed in a variety of other tumors,such as gastric, prostate, lung, colon and ovary carcinoma.

The ERCC1 (19q13) FISH probe has been optimized to detect copy numbers of the
ERCC1 gene region at 19q13. The ZNF443 (19p13) probe is included to facilitate
chromosome identification.

The ERBB2 (17q12) FISH probe is optimized to detect copy numbers of the ERBB2
gene region at region 17q12. The chromosome 17 satellite enumeration probe (SE17) at D17Z1 is included to facilitate chromosome identification/enumeration.

REFERENCES
Olaussen et al, 2006, N. Engl. J. Med. 335; 983-991.
Ceppi et al, 2006, Ann. Oncol. 17; 1818-1825.

REFERENCES
Pauletti et al, 1996, Oncogene, 13: 63-72.
Xing et al, 1996, Breast Cancer Res Treat, 39: 203-212.

D19S1025

D17Z1

SHGC-85693

17q12

17

ZNF443ERBB2490 kB

19p13.2

460 kB

D19S671E

SHGC-5877

D17S1179

19q13.3

19

460 kB
RH47033

ERCC1* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
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254

A

D

V

A

N

C

E

D

S

T

A

I

N

I

ETV6 / RUNX1

N

G

-

R

U

O

P

R

O

B

E

S

ETV6 BreakETV6 / RUNX1 t(12;21)
Fusion probe hybridized topatient material showingt(12;21) translocation(2RG1R1G).

ETV6 (12p13) Break probehybridized to patient material
showing a translocation
involving the ETV6 region at
12p13 (1RG1R1G).

Material kindly provided by
Dr. Balogh, Budapest.

Image kindly provided by
Magret Ratjen, Kiel.

ETV6 / RUNX1 t(12;21) Fusion

ETV6 (12p13) Break

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10401

Green/Red

100 µL

RUO

KI-10403

Green/Red

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUND

The t(12;21), a cryptic translocation rarely observed by conventional cytogenetics,
was first identified by fluorescence in situ hybridization (FISH). In ALL blasts, thistranslocation fuses the 5’ part of the ETV6 (previously known as TEL) gene withalmost the entire RUNX1 (previously known as AML) (CBFA2) gene, producing thechimeric transcript ETV6-CBFA2. The t(12;21) (p13;q22) has also been identified
as the most frequent chromosomal abnormality in childhood ALL, affecting 20% to
25% of B-lineage cases.

ETV6 (previously known as TEL) gene is the abbreviation for -ETS variant 6- gene.
It encodes an ETS family factor which functions as a transcriptional repressor inhematopoiesis and in vascular development. The gene is located on chromosome
12p13, and is frequently rearranged in human leukemias of myeloid or lymphoidorigins. Also systematic deletion of the normal ETV6 allele in patients with ETV6RUNX1 fusions can be found. The ETV6 Break FISH probe is optimized to detect
translocations involving the ETV6 region at 12p13 in a dual-color, split assay on
metaphase/interphase spreads and bone marrow cells.

The ETV6 / RUNX1 t(12;21) specific FISH probe is optimized to detect thereciprocal translocation t(12;21) (p13;q22) in a dual-color, dual-fusion assay.

REFERENCES
Golub et al, 1995, PNAS 92; 4917-4921.
Ford et al, 2001, Blood 98; 558-564.

REFERENCES
Romana et al, 1995, Blood, 85; 3662-3670.

12p13
12p13

RH39900

D21S325500 kB

RH39900

ETV6
(TEL)

21q22

1200 kB21

RUNX1(AML1)

RH913431380 kB

ETV6
RH53036

RH65799

SHGC-9898

RH76656

550 kB

12

12* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

255

A

D

V

A

N

C

E

D

S

T

A

I

N

I

EWSR1 / NFATC

N

G

-

R

U

O

P

R

O

B

E

S

EWSR1 BreakFISH result of the EWSR1/NFATC2 t(20;22) DC,
S-Fusion probe.

EWSR1 (22q12) breakprobe hybridized to a tissue
section showing co-localized
and split signals.

EWSR1 / NFATC2 t(20;22) Dual-Color, Single-Fusion

EWSR1 (22q12) Break

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10751

Green/Red

100 µL

RUO

KI-10750

Green/Red

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUND

Ewing’s sarcoma is the second most frequent primary bone cancer. In most casesa translocation involving the EWSR1 gene at 22q12 and the FLI1 gene at 11q24 isobserved. Several other translocation partners of the ETS gene family can also be
involved. The first non-ETS family translocation partner described is the NFATC2
gene (nuclear factor of activated T-cells, cyto-plasmic, calcineurin-dependent 2) at
20q13.

Ewing’s sarcoma is the second most frequent primary bone cancer. In most casesa translocation involving the EWSR1 gene at 22q12 and the FLI1 gene at 11q24 areobserved, but several other translocation partners (ERG, ETV1, FEV, and E1A3) can
also be involved.
The EWSR1 (22q12) Break probe is optimized to detect translocations involving
the EWSR1 gene region at 22q12 in a dual-color, split assay on paraffin embedded
tissue sections.

The EWSR1 / NFATC2 t(20;22) Dual-Color Single-Fusion probe is optimized todetect the t(20;22)(q13;q12) involving the NFATC2 (20q13) and EWSR1 (22q12)
gene regions in a dual-color, single fusion assay on paraffin embedded tissue
sections.

REFERENCES
Zucman-Rossi, et al, 1998, PNAS, 95; 11786-11791.
Bernstein et al, 2006, Oncologist, 11; 503-519.

REFERENCES
Szuhai et al, 2009, Clin Cancer Res, 15; 2259-2268.
Zucman-Rossi et al, 1998, PNAS, 95; 11786-11791.
Bernstein et al, 2006, Oncologist, 11; 503-519.

RH120772

750 kB
22q12

D22S448

EWSR1

SHGC-103388

22

RH120772

SHGC-105635

D22S1554

425 kB

750 kB
480 kB

22q12

20q13.2

20

D22S448EWSR1

NFATC2
D20S857

22* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

256

A

D

V

A

N

C

E

D

S

T

A

I

N

I

FGFR1 Break

N

G

-

R

U

O

P

R

O

B

E

S

FGFR2 / SE 10
FGFR1 (8p11) Break probehybridization to a tissue
section showing a normal
pattern.

FGFR2 (10q26) / SE 10
CODE

COLOR

FORMATSTATUS

KI-10757

Green/Red

100 µLRUO

MENURESEARCH
BACKGROUND
It is well documented that dysregulation of FGF-FGFR signaling via amplification,
point mutation or translocations may have an important role in tumor development
and progression. Alterations in FGFRs are associated with a number of humancancers, including lung, myeloma, breast, gastric, colon, bladder, pancreatic, andhepatocellular carcinomas. A growing body of preclinical data demonstrates
that inhibition of FGFR signaling can result in antiproliferative and/or pro-apoptic
effects, thus confirming the validity of the FGFR / FGFR axis as a potential
therapeutic target.

FGFR1 (8p11) Break
CODE

COLOR

FORMATSTATUS

KI-10737

Green/Red

100 µLRUO

MENURESEARCH

The FGFR2 (10q26) FISH probe is optimized to detect copy numbers of the FGFR2
gene region at region 10q26. The Chromosome 10 Satellite Enumeration (SE) probe
is included to facilitate chromosome identification.

BACKGROUNDFGFR1 has been implicated in the tumorigenesis of haematological malignancies,
where it is frequently involved in balanced chromosomal translocations,
including cases of chronic myeloid leukemia (BCR-FGFR1 fusion) and the 8p11
myeloproliferative syndrome/stem cell leukemia-lymphoma syndrome, which
is characterized by myeloid hyperplasia and non-Hodgkin’s lymphoma withchromosomal translocations fusing several genes, the most common being
a fusion between ZNF198 and FGFR1.“The FGFR1 (8p11) Break FISH probe is
optimized to detect translocations involving the FGFR1 gene region at 8p11 in adual-color assay on FFPE tissue sections.

REFERENCES
Brooks et al, Clin Cancer Res. 2012; 18:1855.
Dutt et al, PLoS ONE 6: e2035.1
Kunii et al, Cancer Res. 2008; 68:2340-8.
Liang et al, Clin Cancer Res. 2013;19: 2572
Liao et al, Cancer Res. 2013;73:5195-205.
Weiss et al, Sci Transl Med. 2010; 2:62ra93.

REFERENCES
Smedley et al, 1998, Hum Mol Genet., 7; 627-642.
Sohal et al, 2001, Genes Chrom. Cancer, 32; 155-163.
Kwak et al, J Clin Oncol., 27(26); 4247-53.

D10Z1

RH103611

FGFR2
RH62328
10q26

520 kB108p11.2415 kB

RH76128

RH7851FGFR1
SHGC-103442

420 kB
SHGC-2804

8* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

257

A

D

V

A

N

C

E

D

S

T

A

I

N

I

FGFR3 / IGH

N

G

-

R

U

O

P

R

O

B

E

S

FGFR4 / 5q11.2
FGFR3 / IGH t(4;14) Fusion
probe hybridized to MM
patient material showingt(4;14) translocation(2RG1R1G).

FGFR4 (5q35) / 5q11.2
CODE

COLOR

FORMATSTATUS

KI-10756

Green/Red

100 µLRUO

MENURESEARCH
Image kindly provided by
Prof. Jauch, Heidelberg.

BACKGROUND
It is well documented that dysregulation of FGF-FGFR signaling via amplification,
point mutation or translocations may have an important role in tumor development
and progression. Alterations in FGFRs are associated with a number of humancancers, including lung, myeloma, breast, gastric, colon, bladder, pancreatic, andhepatocellular carcinomas. A growing body of preclinical data demonstrates
that inhibition of FGFR signaling can result in antiproliferative and/or pro-apoptic
effects, thus confirming the validity of the FGFR / FGFR axis as a potential
therapeutic target.

FGFR3 / IGH t(4;14) Fusion
CODE

COLOR

FORMATSTATUS

KI-10602

Green/Red

100 µLRUO

MENURESEARCH

The FGFR4 (5q35) FISH probe is optimized to detect copy numbers of the FGFR4
gene region at region 5q35. The 5q11.2 probe is included to facilitate chromosome
identification.

BACKGROUND
The t(4;14) translocation is undetectable by conventional cytogenetics. The
breakpoints on chromosome 4 occur within an approximately 113-kb region
located in small part of a conserved gene cluster including the transforming acidic
coiled-coil protein 3 (TACC3), fibroblast growth factor receptor 3 (FGFR3), andmultiple myeloma SET domain-containing protein (MMSET). The translocation isindicative for poor survival and poor response to chemotherapy.

REFERENCES
Brooks et al, Clin Cancer Res. 2012; 18:1855.
Dutt et al, PLoS ONE 6: e2035.1
Kunii et al, Cancer Res. 2008; 68:2340-8.
Liang et al, Clin Cancer Res. 2013;19: 2572
Liao et al, Cancer Res. 2013; 73:5195-205.
Weiss et al, Sci Transl Med. 2010; 2:62ra93.

The FGFR3 / IGH t(4;14)(p16;q32) Fusion specific FISH probe is optimized to detect
the reciprocal translocation t(4;14) in a dual-color, dual-fusion assay.
REFERENCES

HUMC5360

ISL1

Chesi et al, 1997, Nat Genet, 16; 260-264.
Finelli et al, 1999, Blood, 94; 724-732.

4p16

440 kB
5q11.2
D5S1395

D4S992

RH46284

D14S683E

FGFR3
WHSC1

D5S2703150 kB

FGFR41200 kB

IGH

BAC51977S

1420 kB
5q35

14

NSD1

5

14q32

D4S43

RH667904* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

258

A

D

V

A

N

C

E

D

S

T

A

I

N

I

FIP1L1 / CHIC2 /PDGFRA Dual-Color

N

G

-

R

U

O

P

R

O

B

E

S

FIP1L1 / CHIC2 /PDGFRA Triple-ColorFIP1L1 / CHIC2 / PDGFRA(4q12) Deletion, Breakprobe hybridized to a normalinterphase/metaphase(2RG).

FIP1L1 / CHIC2 / PDGFRA(4q12) Deletion, Break
Triple-Color.

FIP1L1 / CHIC2 / PDGFRA (4q12) Deletion, BreakFIP1L1 / CHIC2 / PDGFRA (4q12) Deletion, Break, Triple-Color

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10003

Green/Red

100 µL

RUO

KI-10007Green/Red/Blue

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUND

The deletion of the CHIC2 locus generates a fusion FIP1L1-PDGFRA gene giving
raise to a novel tyrosine kinase. This deletion has been observed in patients with
idiophatic hypereosinophilic syndrome (HES), chronic eosinophilic leukemia (CEL),
systemic mast cell disease, and chronic myeloproiferative disorders (CMPD).

The FIP1L1 / CHIC2 / PDGFRA Triple-Color FISH probe is optimized to detect theCHIC2 deletion at 4q12 associated with the FIP1L1 / PDGFRA fusion in a triplecolor, split assay. It also allows the detection of translocation involving the FIP1L1
and PDGFRA region.

The FIP1L1 / CHIC2 / PDGFRA FISH probe is optimized to detect the CHIC2
deletion at 4q12 associated with the FIP1L1 / PDGFRA fusion in a Dual-Color,
split assay. It also allows the detection of translocation involving the FIP1L1 andPDGFRA region. However, chromosome 4 polyploidy may provide additional signals
not associated with a translocation involving 4q12.

Cools et al, N Engl J Med, 2003, 348; 1201-1214.
Griffin et al, 2003, PNAS, 100;7830-7835.
Gotlib et al, 2004, Blood, 103;2879-2891

REFERENCESREFERENCES

SHGC-68563

SCFD2

Cools et al, N Engl J Med, 2003, 348; 1201-1214.
Godlib et al, Blood, 2004, 103; 2879-2891.

640 kB

FIP1L1
4q12

RH65011

LNX1

D4S461

CHIC2

SHGC-68563

SCFD2

PDGFRAFIP1L1
4q12

SHGC-85185

520 kB

RH65011LNX1KIT

D4S461

CHIC2

460 kB

SHGC-50149

640 kB

SHGC-50170

460 kB

4

SHGC-50149

PDGFRA

SHGC-85185

520 kBKITSHGC-50170

4* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

259

A

D

V

A

N

C

E

D

S

T

A

I

N

I

FOXO1 Break

N

G

-

R

U

O

P

R

O

B

E

S

FUS BreakFOXO1 (13q14) Break probehybridized to patient material(2RG).

FUS (16p11) Break probehybridized to liposarcoma
material.

FOXO1 (13q14) BreakFUS (16p11) Break

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10716

Green/Red

100 µL

RUO

KI-10715

Green/Red

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUND

The t(2;13) is associated with alveolar rhabdomyo-sarcomas. This translocation
results in the formation of a chimeric transcript consisting of the 5’ portion of
PAX3, including an intact DNA-binding domain fused to the FOXO1 gene on
chromosome 13. The t(1;13)(p36;q14) also seen in alveolar rhabdomyosarcomas
results in the fusion of another member of the PAX family, PAX7 to the FOXO1 geneon chromosome 13.

The fused in sarcoma (FUS) gene was originally shown to be rearranged in myxoid
liposarcomas harboring a t(12;16)(q13;p11) translocation. FUS has also beenshown to be involved in other recombinations: with ERG in acute myeloid leukemia
carrying a t(16;21), with ATF1 in band 12q13 in angiomatoid fibrous histiocytoma,
and with CREB3L2 in fibromyxoid sarcoma.
A break or split probe for FUS is best used to analyze translocation of the FUS(16p11) gene on formalin fixed paraffin embedded tissue for routine clinicaldiagnosis.

A break or split probe for FOXO1 is best used to analyze translocation of the
FOXO1 (13q14) gene on formalin fixed paraffin embedded tissue for routine clinicaldiagnosis.

The FUS (16p11) Break probe is optimized to detect translocations involving the
FUS gene region at 16p11 in a dual-color, split assay on metaphase/interphasespreads and paraffin embedded tissue sections.

The FOXO1 (13q14) Break probe is optimized to detect translocations involving the
FOXO1 gene region at 13q14 in a dual-color, split assay on metaphase/interphasespreads and paraffin embedded tissue sections.

REFERENCESREFERENCES

Shing et al, 2003, Cancer Res, 63: 4568-4576.
Storlazzi et al, 2003, Hum. Mol. Genet., 12: 2349-2358.

Barr et al, 1996, Hum. Mol. Genet., 5; 15-21.
Coignet et al, 1999, Genes Chrom. Cancer, 25; 222-229.

D16S2574E

780 kB

RH45178850 kB

16p11.2

RH53132

FUS

13q14

SHGC-106097

FOXO1

550 kB

RH1427716

690 kB

13

RH47854

D16S2933E

D13S1050* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

260

A

D

V

A

N

C

E

D

S

T

A

I

N

I

GATA4 / SE 8

N

G

-

R

U

O

P

R

O

B

E

S

GLI1 / SE 12
GATA4 (8p23) / SE 8 probehybridized to patient material
showing a deletion of the
GATA4 (8p23) region (1R2G).

GLI1 (12q13) / SE 12
hybridized to patient material
showing GLI (12q13)
amplification (3R2G).

Image kindly provided by Dr.
Wenzel, Basel.

GATA4 (8p23) / SE 8

GLI1 (12q13) / SE 12

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-40118

Green/Red

100 µL

RUO

KI-10104

Green/Red

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUND

The deletion of GATA4 (8p23) is found in patients with congenital heart disease.
Besides the deletion, duplications are found of the region flanked by low copy
repeats 8p-OR-REPD (distal) and -REPP (proximal). These recurrent deletions areassociated with a spectrum of anomalies, including developmental delay andneuropsychiatric findings. GATA4 is expressed in adult heart, epithelium andgonads. During fetal development, GATA4 is expressed in yolk sac endoderm andcells involved in heart formation.

Trisomy 12 is the most common numerical chromosomal aberration in patientswith B-cell chronic lymphocytic leukemia (B-CLL). Partial trisomy 12 of the longarm of chromosome 12 consistently includes a smaller region at 12q13-15 and has
been observed in CLL and several other tumors. A number of loci located close toeither MDM2 or CDK4 / SAS, including the genes GADD153, GLI1 (previously known
as GLI), RAP1B, A2MR, and IFNG, were found to be coamplified.
The GLI1 (12q13) specific FISH probe is optimized to detect copy numbers of the
GLI1 gene region at region 12q13. The chromosome 12 Satellite Enumeration FISH
probe (SE 12) D12Z3 is included to facilitate chromosome identification.

The GATA4 (8p23) / SE 8 FISH probe is optimized to detect deletions of the GATA4gene region at 8p23 in a dual-color assay on metaphase/interphase spreads, bloodsmears and bone marrow cells. The Chromosome 8 Satellite Enumeration (SE)FISH probe is included to facilitate chromosome identification.

REFERENCES
Merup et al, 1997, Eur J Haematol, 58; 174-180.
Dierlamm et al., 1997, Genes Chrom Cancer, 20; 155-166.

REFERENCES
Bhatia et al, 1999, Prenat Diagn., 19; 863-867.
Giorda et al, 2007, Hum. Mut., 28; 459-468.
Wat et al, 2009, Am. J. Med. Genet., Part A, 149A; 1661-1677.

D12Z3

D12S1266

12q13

REPD

8p23

270 kB
GLI1
RH75890

3Mb
SE8
RH122631

GATA4

12470 kB

RH121772

REPP

8* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

261

A

D

V

A

N

C

E

D

S

T

A

I

N

I

HIRA / SHANK3

N

G

-

R

U

O

P

R

CODE

COLOR

FORMATSTATUS

KBI-20000G

Green

10 testRUO

KBI-20000R

Red

10 testRUO

KI-20000GGreen

100 µL

RUO

KI-20000RRed

100 µLRUO

RESEARCH

HIRA (22q11) / 22q13 (SHANK3)
CODE

COLOR

FORMATSTATUS

KI-40103

Green/Red

100 µLRUO

MENURESEARCH
BACKGROUND
The DiGeorge HIRA (TUPLE) probe targets a putative transcriptional regulator(TUPLE1 or HIRA, HIR histone cell cycle regulation defective homolog A) which
also has been identified to lie within the commonly deleted region DiGeorge
syndrome. This probe is located distally to the “N25” probe.
The DiGeorge HIRA region probe is optimized to detect copy numbers of the HIRA
gene region at 22q11.2. The SHANK3 probe at 22q13 is serving as internal control.
REFERENCES
Lorain at al, 1996, Genome Res, 6; 43-50.

D22S1660

DGCR2
"N25"

CLTCL1
D22S1646
D22S553

HIRA

220 kB

D221668
22q13
RH8457ARSASHANK3E

All Human Centromere Green

MENU

22

B

Human Centromere
DiGeorge HIRA (22q11) /22q13 (SHANK3) probehybridized to a normal
metaphase (2R2G).

22q11.2O

130 kB

RH38881* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
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262

S

A

D

V

A

N

C

E

D

S

T

A

I

N

I

IGF1R / 15q11

N

G

-

R

U

O

P

R

O

B

E

IGH Break
IGF1R (15q26) / 15q11
probe hybridized to patientmaterial showing a deletionof the IGF1R gene region at
15q26 (1R2G).

IGH (14q32) Break probehybridized to patient material
showing a partial deletion of
14q32 (1RG1R).

IGF1R (15q26) / 15q11

IGH (14q32) Break

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-40116

Green/Red

100 µL

RUO

KI-10601

Green/Red

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUND

Congenital diaphragmatic hernia (CDH) is a severe, life-threatening, congenital
anomaly characterized by variable defect in the diaphragm, pulmonary hypoplasia,
and postnatal pulmonary hypertension. Deletion of the IGF1R (insulin-like growth
factor 1 receptor) gene region at 15q25 is the most frequent anomaly found in
CDH. The type 1 IGF receptor at 15q26 is required for normal embryonic andpostnatal growth. Deletions, but also gain of an approximately 5 Mb region
including the IGF1R gene has been found to have a profound effect on prenatal andearly postnatal growth.

Multiple myeloma is characterized by complex rearrangements involving the IgHgene, particularly at the constant locus. The IgH rearrangement provides a usefulmarker of clonality in B-cell malignancies and amplification of this rearrangement
is the method of choice to monitor the residual tumor cells in multiple myeloma.

The IGF1R (15q26) specific FISH probe is optimized to detect copy numbers of the
IGF1R gene region at region 15q26. The 15q11 (SNRPN / UBE3A) specific region
probe is included to facilitate chromosome identification.

Taniwaki et al, 1994, Blood, 83; 2962-1969.
Gozetti et al, 2002, Cancer Research, 62; 5523-5527.

The IGH (14q32) break probe is optimized to detect translocations involving the
IGH gene region at 14q32 in a dual-color, split assay.
REFERENCESREFERENCES

D14S683E

Faivre et al, 2002, Eur, J, Hum, Genet., 10; 699-706.
Okubo et al, 2003, J. Clin. Endocrinol. Metab, 88; 5981-5988.

660 kB
RH44825

IGH
SHGC-170017

RH54346

14q32

14

SNRPN

460 kB
D14S1420

890 kB
15q11.2

UBE3A
D15S10SHGC 154952
15q26

15

IGF1R

S

540 kB

SHGC-3827* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

263

A

D

V

A

N

C

E

D

S

T

A

I

N

I

IGH Break (tissue)

N

G

-

R

U

O

P

R

O

B

E

S

IRF4 / DUSP22 BreakHybridization of IGH breakprobe to a tissue section
showing“normal andaberrant pattern (2RG)(1RG1R1G).

IRF4 / DUSP22 (6p25) Break.

Image kindly provided
by Hopital Universitario
Marqués de Valdecilla,
Satander.

IGH (14q32) Break (tissue)

IRF4 / DUSP22 (6p25) Break

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10729

Green/Red

100 µL

RUO

KI-10613

Green/Red

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUND

Chromosomal rearrangements involving the immunoglobulin heavy chain
gene (IGH) at 14q32 are observed in 50% of patients with B-cell non-Hodgkin’s
lymphoma (NHL) and many other types of Lymphomas. More than 50 translocation
partners with IGH have been described. In particular t(8;14) is associated with
Burkitt’s lymphoma, t(11;14) is associated with Mantle cell lymphoma, t(14;18) isobserved in a high proportion of follicular lymphomas and t(3;14) is associatedwith Diffuse Large B-Cell Lymphoma.

Rearrangements of the 6p25.3 locus define a subtype of CTCL. Genes
rearranged at the 6p25.3 locus are IRF4 (also known as MUM1) and the DUSP22.
Rearrangements of the 6p25.3 locus have also been described to occur in high andlow grade B-cell lymphomas, myeloma and chronic B-cell lymphoid leukemia.

The IGH (14q32) Break probe is optimized to detect translocations involving the
IGH gene region at 14q32 in a dual-color, split assay.

The IRF4 / DUSP22 (6p25) Break FISH probe is optimized to detect translocations
involving the IRF4 / DUSP22 gene region at the 6p25.3 locus in a dual-color assay
on metaphase/interphase spreads, blood smears, bone marrow cells and lymph
node biopsies.

The IRF4 / DUSP22 (6p25) Break FISH probe detects both rearrangements involving
IRF4 and DUSP22, but does not distinguish them from each other.

REFERENCES
Taniwaki et al, 1994, Blood, 83: 2962-1969.
Gozetti et al, 2002, Cancer Research, 62: 5523-5527.

REFERENCES
Bisig et al., Best Pract Res Clin Haematol, 2012, 25; 13-28.
Feldman et al., Blood, 2011, 117; 915-919.
Karai et al., Am J Surg Pathol, 2013 [Epub ahead of print].
Pham-Ledard et al., J Invest Dermatol, 2010, 130; 816-825.
Salaverria et al., Blood, 2011, 118; 139-147.
Wada et al., Mod Pathol, 2011, 24; 596-605.

D14S683E

660 kB
RH44825

IGH
SHGC-170017
14q32

14

460 kB
D14S1420

6p25

RH12503
RH40877

100 kB

DUSP22
IRF4
RH40931500 kB
D6S1600

6* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

264

A

D

V

A

N

C

E

D

S

T

A

I

N

I

JAK2 Break

N

G

-

R

U

O

P

R

O

B

E

S

KMT2A / AFF1
JAK2 (9p24) Break probehybridized to bone marrow
sample (2RG).

KMT2A / AFF1 t(4;11) Fusion
probe. Standard t(4;11)
2 Fusion, 1 Red, 1 Green(2F1R1G).

Image kindly provided by
Dr. Christine Harrison,
Newcastle.

JAK2 (9p24) BreakKMT2A / AFF1 t(4;11) Fusion

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10012

Green/Red

100 µL

RUO

KI-10404

Green/Red

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUND

Janus Kinase 2 (JAK2) is a tyrosine kinase involved in cytokine signaling.
Mutations and translocations involving the JAK2 gene region are observed inmyeloproliferative neoplasms. The common JAK2617V>F point mutation andtranslocations results in constitutive activation of JAK2. Translocations aredescribed with the following fusion partners: PCM1, BCR, ETV6 (TEL), SSBP2 and
3q21. Patients with the JAK2617V>F point mutation can also exhibit a numerical
gain of the gene.

The t(4;11) KMT2A / AFF1 is the most frequently (approximately 66% according
to Meyer et al.) observed translocation involving the KMT2A gene resulting in
ALL. The KMT2A / AFF1 translocation results in the generation of fusion proteins
KMT2A / AFF1 and AFF1 / KMT2A; both seem to have leukemogenic properties.
Furthermore, MECOM (3q26) is one of the targets of the KMT2A oncoproteins,which increased expression correlates with unfavorable prognosis in Acute
Myeloid Leukemia.

The JAK2 (9p24) Break FISH probe is optimized to detect translocations involving
the JAK2 gene region at region 9p24 in a dual-color, split assay on metaphase/interphase spreads. The JAK2 (9p24) Break FISH probe can not be used to detect
point mutations, and it has not been optimized to detect gene amplifications.jfeld
V et al, 2007, Exp Hematol, 35; 1668-1676.

The KMT2A / AFF1 t(4;11) Fusion FISH probe is optimized to detect translocations
involving the KMT2A (previously known as MLL) and AFF1 gene regions at 4q21-22
and 11q23 in a dual-color, fusion assay on metaphase/interphase spreads, bloodsmears and bone marrow cells.
REFERENCESREFERENCES

Harrison CJ et al, 2010, Br J Haem, 151; 132-142.
Arai S et al, 2011, Blood, 117; 6304-6314
Meyer C et al, 2009, Leukemia, 23; 1490-1499.

Smith C et al, 2008, Hum Pathol, 39; 795-810.
Poitras J et al, 2008, Genes Chromosomes Cancer, 47; 884-889.
9p24

SHGC-149694

D4S2462550 kB
RH63147

JAK2

D11S3416

RH92501

525 kB
4q21-22

D9S1969

AFF1

KMT2A
(MLL)

950 kB
11q23

D11S2682

11

9RH59505

4* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

265

1030 kB

A

D

V

A

N

C

E

D

S

T

A

I

N

I

KMT2A / MLLT1

N

G

-

R

U

O

P

R

O

B

E

S

KMT2A / MLLT3
KMT2A / MLLT1 t(11;19)
Fusion probe hybridized topatient material showingt(11;19) translocation(2RG1R1G).

KMT2A/MLLT3 t(9;11)
Fusion probe hybridized topatient material showingt(9;11) translocation(2RG1R1G).

Image kindly provided by Dr.
Mohr, Dresden.

KMT2A / MLLT1 t(11;19) Fusion

KMT2A / MLLT3 t(9;11) Fusion

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10307

Green/Red

100 µL

RUO

KI-10308

Green/Red

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUND

One of the relatively frequently observed translocations (around 10 %) in AML and
ALL involves the genes KMT2A (previously known as MLL) and MLLT1 (aka ENL)
at 11q23 and 19p13. The KMT2A / MLLT1 translocation results in the generationof fusion protein that retains the MLL N-terminus, including both an A-T hookdomain and a region similar to mammalian DNA methyltransferase. There areseveral breakpoints within the MLLT1 gene described, without clear differencesin clinicohematologic features. The KMT2A / MLLT1 Fusion probe is optimized
to detect translocations involving the KMT2A and MLLT1 gene regions at 11q23
and 19p13 in a dual-color, fusion assay on metaphase/interphase spreads, bloodsmears and bone marrow cells in a dual-color, fusion assay.

Chromosomal rearrangements involving the mixed lineage leukemia (MLL) geneat 11q23 are frequently observed in adult and childhood acute leukemia and are,in general, associated with poor prognosis. However, children with Acute Myeloid
Leukemia (AML) carrying the t(9;11) KMT2A / MLLT3 (aka AF9) translocation havebeen described to be more sensitive to chemotherapy than patients with other
11q23 rearrangements.
The KMT2A / MLLT3 Fusion FISH probe is optimized to detect translocations
involving the KMT2A (previously known as MLL) and MLLT3 gene regions at 11q23
and 9p21 in a dual-color fusion assay on metaphase/interphase spreads, bloodsmears and bone marrow cells.

REFERENCESREFERENCES

Mitterbauer-Hohdanner G et al, 2004, Eur J Clin Invest, 34; 12-24.
Meyer C et al, 2009, Leukemia, 23; 1490-1499.
Fu JF et al, 2007, Am J Clin Pathol, 127; 24-30.

19p13.3

Von Lindern et al, 1992, Mol. Cell. Biol.,12; 1687-1697.
Ageberg et al, 2008, Gen. Chrom. Canc., 47; 276-287.
Chi et al, 2008, Arch. Pathol. Lab. Med.,132; 1835-1837.
HUMUT841

SHGC-51155
9p21

D11S3416

KMT2A
(MLL)
11q23

MLLT1
(ENL)
1030 kB

19

1460 kB
MLLT3
(AF9)

1080 kB

D11S3416

RH80857

KMT2A
(MLL)

RH93561

D11S2682
11q23

11

9

D11S2682

11* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

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1030 kB

A

D

V

A

N

C

E

D

S

T

A

I

N

I

KMT2A / MLLT4

N

G

-

R

U

O

P

R

O

B

E

S

KMT2A / SE 11
KMT2A / MLLT4 t(6;11)
Fusion probe hybridized
to patient material
showing 47,XX,t(6;11)(q27;q23),+der(6)t(6;11)(q27;q23).

KMT2A (11q23) / SE
11 hybridized to normalinterphases (2R2G).

KMT2A / MLLT4 t(6;11) Fusion

KMT2A (11q23) / SE 11

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10309

Green/Red

100 µL

RUO

KI-10711

Green/Red

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUND

One of the relatively frequently observed translocations in AML involves the genes
KMT2A and MLLT4 (previously known as AF6) at 11q23 and 6q27. The KMT2A/ MLLT4 translocation results in the generation of fusion protein that retains theKMT2A N-terminus, including both an A-T hook domain and a region similar to
mammalian DNA methyltransferase. The breakpoint region of the MLLT4 gene islocated within intron 1 and downstream of the initiation codon.

Deletions of the long arm of chromosome 11 (11q) have been noted in primaryneuroblastomas. It is assumed that a tumor suppressor gene mapping within
11q23.3 is commonly inactivated during the malignant evolution of a large
subset of neuroblastomas, especially those with unamplified MYCN. The KMT2A(11q23) FISH probe is optimized to detect amplification or deletion involving
the KMT2A gene region at 11q23 in a dual-color assay. The Chromosome 11
Satellite Enumeration probe (SE 11) at D11Z1 is included to facilitate chromosome
identification.

The KMT2A / MLLT4 t(6;11) Fusion FISH probe is optimized to detect
translocations involving the KMT2A (previously known as MLL) and MLLT4 generegions at 11q23 and 6q27 in a dual-color, fusion assay on metaphase/interphasespreads, blood smears and bone marrow cells.

REFERENCES
Guo et al, 1999, Oncogene, 18: 4948-4957.
Maris et al, 2001, Med Pediatr Oncol, 36: 24-27.

REFERENCES
Mitterbauer-Hohdanner G et al, 2004, Eur J Clin Invest, 34; 12-24.
Meyer C et al, 2009, Leukemia, 23; 1490-1499.

SE11
SHGC-85140
D11S3416

SHGC-77766

11q23

KMT2A
(MLL)
1480 kB
MLLT4
(AF6)
6q27

6

11q23

1030 kB

11

KMT2A
(MLL)

720 kB

D11S1930

D11S2682

11

SHGC-144743* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

267

A

D

V

A

N

C

E

D

S

T

A

I

N

I

KMT2A Break

N

G

-

R

U

O

P

R

O

B

E

S

MAF/ IGH
Hybridization of KMT2A
probe to a metaphasespread showing normal
pattern (2F).

MAF / IGH t(14;16) Fusion
probe hybridized to patientmaterial showing a deletionof the MAF gene region at
16q23 (2R1G).

KMT2A (11q23) BreakMAF / IGH t(14;16) Fusion

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10303

Green/Red

100 µL

RUO

KI-10610

Green/Red

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUND

The human chromosome band 11q23 is associated with a high number ofrecurrent chromosomal abnormalities including translocations, insertions, anddeletions. It is involved in over 20% of acute leukemias. The KMT2A (previously
known as MLL) gene, named for its involvement in myeloid (usually monoblastic)
and lymphoblastic leukemia, and less commonly in lymphoma, is located in the
11q23 breakpoint region. Leukemias involving the KMT2A gene usually have a poor
prognosis.

Abnormalities of 16q are important recurrent events in multiple myeloma (MM).
The t(14;16)(q32;q23) is a karyotypically silent translocation that is associatedwith the ectopic expression and dysregulation of MAF mRNA. Translocations thatbracket the MAF locus (dispersed over 500 kb) are estimated to be present in up to
25% of plasma cell myelomas.
The MAF / IGH t(14;16) specific FISH probe is optimized to detect the reciprocaltranslocation t(14;16) in a dual-color, dual-fusion assay on metaphase/interphasespreads, blood smears and bone marrow cells.

The KMT2A (11q23) Break FISH probe is optimized to detect translocations
involving the KMT2A gene region at 11q23 in a dual-color split assay.

REFERENCESREFERENCES

Chesi et at, 1998, Blood 91; 4457-4463.
Sawyer et al, 1998, Blood 92; 4269-4278.

Kobayashi et al, 1993, Blood, 81; 3027-3022
Martinez-Climent et al, 1995, Leukemia, 9; 1299-1304.

SHGC-105199
D14S683E

530 kB
SHGC-78905

WWOX
SHGC-85140

IGH

310 kB

16q23

RH92387

14q32

KMT2A

14

SHGC-111513

RH66790

16

SHGC-79420

D11S1930* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

268

Gap: 2.2 MB

RH69965

265 kB

11q23

11

MAF

1420 kB

500 kB

A

D

V

A

N

C

E

D

S

T

A

I

N

I

MAFB /IGH

N

G

-

R

U

O

P

R

O

B

E

S

MALT1 BreakThe MAFB / IGH t(14;20)
Fusion FISH probe hybridized
to patient material showing
a complex pattern with at(14;20) translocation.

MALT1 (18q21) Break probehybridized to patient material
showing a translocation at
18q21 (1RG1RG).

Image kindly provided by
Erasmus Medical Center,
Rotterdam.

MAFB / IGH t(14;20) Fusion

MALT1 (18q21) Break

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10510

Green/Red

100 µL

RUO

KI-10608

Green/Red

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUND

The immunoglobulin heavy chain (IGH) gene at 14q32 is an important causeof genetic deregulation in MM. Among the known fusion partners for the IGH(previously known as IGH@) gene, reciprocal translocation with the MAFB gene at
20q12 is relatively rare in MM (~2% occurrence). However, the MAFB / IGH t(14;20)translocation is associated with poor prognosis in multiple myeloma patients.

Low grade malignant lymphomas arising from mucosa associated lymphoidtissue (MALT) represent a distinct clinicopathological entity. The three majortranslocations seen in MALT lymphomas are t(11;18)(q21;q21) / API2-MALT1,
t(14;18)(q32;q21) / IGH-MALT1 and t(1;14)(p22;q32) / IGH-BCL10. A break or split
probe for MALT1 (18q21) is best used to analyze translocation of the MALT1 geneon formalin fixed paraffin embedded tissue for routine clinical diagnosis.

The MAFB / IGH t(14;20) Fusion FISH probe is optimized to detect the reciprocaltranslocation t(14;20) in a dual-color, dual-fusion assay on metaphase/interphasespreads and bone marrow cells.

Kreatech has optimized this FISH probe for the specific use on cell material (KBI10608), or for the use on tissue (KBI-10731).

REFERENCESREFERENCES

Boersma-Vreugdenhil GR et al, 2004, Br J Haematol, 126; 355-363.
Bergsagel PL et al, 2005, JCO, 23; 6333-6338.

Morgan et al, 1999, Cancer Res, 59; 6205-6213.
Dierlamm et al, 2000, Blood, 96; 2215-2218.

WI-5827

RH123327

D14S683E

D18S881515 kB

IGH

20

14q32

14

20q12

1420 kB

345 kB

MALT1
18q21

MAFB

RH93602680 kB528 kB

18

RH10684

RH103885

RH66790* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

269

A

D

V

A

N

C

E

D

S

T

A

I

N

I

MALT1 Break (tissue)

N

G

-

R

U

O

P

R

O

B

E

S

MDM2 / SE 12
MALT1 (18q21) Break tissue
probe hybridized to paraffin
embedded material (2RG).

MDM2 (12q15) / SE
12 Amplification probehybridized to patient material
showing amplification of the
MDM2 gene region at 12q15.

MALT1 (18q21) Break (tissue)

MDM2 (12q15) / SE 12

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10731

Green/Red

100 µL

RUO

KI-10717

Green/Red

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUND

Low grade malignant lymphomas arising from mucosa associated lymphoidtissue (MALT) represent a distinct clinicopathological entity. The three majortranslocations seen in MALT lymphomas are t(11;18)(q21;q21) / API2-MALT1,
t(14;18)(q32;q21) / IGH-MALT1 and t(1;14)(p22;q32) / IGH-BCL10. A break or split
probe for MALT1 (18q21) is best used to analyze translocation of the MALT1 geneon formalin fixed paraffin embedded tissue for routine clinical diagnosis.

Well-differentiated liposarcoma/atypical lipomatous tumor and dedifferentiatedliposarcoma are among the most common malignant soft tissue tumors presented
in older adults. These tumors can be difficult to distinguish from benign lipomatous
neoplasms and other high-grade sarcomas.
Amplification of the MDM2 gene has been identified in lipomatous neoplasms.
The use of fluorescence in situ hybridization in identifying MDM2 amplification
has made the MDM2 amplification probe a valuable diagnostic tool in welldifferentiated liposarcomas/atypical lipomatous tumors. The MDM2 (12q15) FISH
probe is optimized to detect copy numbers of the MDM2 gene region at region
12q15.

The MALT1 (18q21) Break probe is optimized to detect translocations involving the
MALT1 gene region at 18q21 in a dual-color, split assay.
Kreatech has developed this probe for the specific use on cell material (KBI10608), or for the use on tissue (KBI-10731).

The chromosome 12 satellite enumeration probe (SE 12) at D12Z3 is included tofacilitate chromosome identification.

REFERENCES
Morgan et al, 1999, Cancer Res, 59; 6205-6213.
Dierlamm et al, 2000, Blood, 96; 2215-2218.

WI-5827
D18S881

REFERENCES
Uchida et al, 2010, Cancer Genet Cytogenet 203; 324-327.
Lucas et al, 2010, Am J Surg Pathol 34: 844-851.
Weaver et al, 2008, Mod Pathol 21: 943-949.
Mitchell et al, 1995, Chrom. Res., 3; 261-262.
Reifenberger et al, 1996, Cancer Res., 15; 5141-5145.

345 kB

MALT1
18q21

RH93602680 kB

18

RH103885

D12Z3

12q15

RH28583

MDM2

530 kB

D12S1497

12* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

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A

D

V

A

N

C

E

D

S

T

A

I

N

I

MDM4 / SE 1

N

G

-

R

U

O

P

R

O

B

E

MECOM BreakMDM4 (1q32) / SE 1 probehybridized to paraffin
embedded tissue (2R2G).

MECOM t(3;3);inv(3) (3q26)
Break probe hybridized topatient material showing arearrangement involving the
MECOM gene region at 3q26
(1RG1R1G).

Image kindly provided by Dr.
Reed, London.

MDM4 (1q32) / SE 1

MECOM t(3;3); inv(3) (3q26) Break

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10736

Green/Red

100 µL

RUO

KI-10204

Green/Red

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUND

MDM4 (MDM4 p53 binding protein homolog (mouse), also known as MDMX,
murine double minute gene) is a relative of MDM2 that was identified on the basisof its ability to physically interact with TP53. MDM4, like MDM2, acts as a key
negative supressor of TP53 by interfering with its transcriptional activity. MDM4
amplification and/or overexpression occurs in several diverse tumors. Studies
showed an increased MDM4 copy number in 65% of human retinoblastomas
compared to other tumors, qualifying MDM4 as a specific chemotherapeutic target
for treatment of this tumor.

The inv(3)(q21;q26) is a recurrent cytogenetic aberration of myeloid malignancy
associated with fusion of MECOM (EVI) and RPN1. Genomic breakpoints in 3q26
are usually located proximal to the MECOM locus, spanning a region of several
hundred kilobases. Other recurrent and sporadic rearrangements of 3q26 also
cause transcriptional activation of MECOM including the translocations t(3;3)(q21;q26) and t(3;21)(q26;q22). Breakpoints in the latter rearrangements spana wider genomic region of over 1 megabase encompassing sequences distal to
MECOM and neighboring gene MDS1.

The MDM4 (1q32) FISH probe is designed as a dual-color assay to detect
amplification at 1q32. The chromosome 1 Satellite Enumeration (SE 1) probe at
1qh is included to facilitate chromosome identification.

The MECOM t(3;3) inv(3) Break, dual-color FISH probe is optimized to detect
the inversion of chromosome 3 involving the MECOM gene region at 3q26 in adual-color, split assay on metaphase/interphase spreads, blood smears and bonemarrow cells.

REFERENCESREFERENCES

Riemenschneider et al, 1999, Cancer Res. 59“; 6091-6096.
Danovi et al, 2004, Mol.Cell.Biol. 24; 5835-5843.

De Braekeleer et al, 2011, Anticancer Res, 31; 3441-3448
Shearer B. et al, 2010, Am J Hematol, 85:569-574
Cui W. et al, 2011, Am J Clin Pathol, 136; 282-288
De Melo V. et al, 2007, Leukemia aop, 13 Sep, 1-4
Levy E. et al, 1994, Blood, 83; 1348-1354
Wieser R et al, 2003, Haematologica, 88; 25-30

1qh
D3S1243
STSG27747

470 kB
SHGC-85783

MDM4

S

MECOM
(EVI1)

450 kB

GAP: 370 kB

1q32
RH17919
SHGC-148562

1

3q26.23TERC

590 kB

RH10606* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

271

A

D

V

A

N

C

E

D

S

T

A

I

N

I

MECOM Break Triple-Color

N

G

-

R

U

O

P

R

O

B

E

MECOM / RUNX1MECOM t(3;3);inv(3) (3q26)
Break probe hybridized topatient material showing arearrangement involving the
MECOM gene region at 3q26
(1RG1R1G).

MECOM / RUNX1 Fusion
probe hybridized to patientmaterial showing t(3;21)(2F1R1G).

Image kindly provided by Dr.
Reed, London.

Image kindly provided by Dr.
Mohr, Dresden.

MECOM t(3;3); inv(3) (3q26) Break, Triple-Color

MECOM / RUNX1 t(3;21) Fusion

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10205

Green/Red/Blue

100 µL

RUO

KI-10310

Green/Red

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUND

The MECOM t(3;3); inv(3)(3q26) Break Triple-Color FISH probe is optimized todetect the inversion of chromosome 3 involving the MECOM (previously known
as EVI) gene region at 3q26 in a dual-color, split assay on metaphase/interphasespreads, blood smears and bone marrow cells. By using a third color breakpoint
variations can also be easily observed.

The MECOM (EVI1, 3q26) / RUNX1 (AML1, 21q22) translocation, t(3;21), is
consistently found in blastic crisis of chronic myelocytic leukemia (CML) andmyelodysplatic syndromederived leukemias. The translocation produces RUNX1/ MECOM chimeric transcription factor and is thought to play important rolesin acute leukemic transformation of hemopoietic stem cells. The MECOM /RUNX1 t(3;21) Fusion specific FISH probe is optimized to detect the reciprocaltranslocation t(3;21) in a dual-color, dual-fusion assay on metaphase/interphasespreads, blood smears and bone marrow cells.

REFERENCES
De Braekeleer et al, 2011, Anticancer Res, 31; 3441-3448;
Levy E. et al, 1994, Blood, 83; 1348-1354
Cui W. et al, 2011, Am J Clin Pathol, 136; 282-288
Wieser R et al, 2003, Haematologica, 88; 25-30
De Melo V. et al, 2007, Leukemia aop, 13 Sep, 1-4
Shearer B. et al, 2010, Am J Hematol, 85:569-574

REFERENCES
Mitani et al., EMBO, 1994, Vol 13, 504-510
Tanaka et al., Mol Cell Biol, 1995, 2383-2392

D21S325
RH103072

420 kB
D3S1243
RH67219

MECOM(EVI1)

3q26.2

3

MECOM(EVI1)RUNX1(AML1)

SHGC-9898

GAP: 370 kB

RH17919590 kB
3q26.2

RH10606
RH111834

RH123089

21

SHGC-85783

GAP: 590 kB

RH17919

TERC

21q22

470 kB3

550 kBTERC

590 kB

RH10606* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent272

1380 kB

S

A

D

V

A

N

C

E

D

S

T

A

I

N

I

MET / SE 7

N

G

-

R

U

O

P

R

O

B

E

S

MYC (8q24) BreakHybridization of MET
Amplification probe to atissue section showing MET
amplification.

MYC (8q24) Break probehybridized to patient material
showing a 8q24 proximal
break (1GBR1G1BR).

Image kindly provided by
Prof. Siebert, Kiel.

MET (7q31) / SE 7

MYC (8q24), Triple-Color, Break

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10719

Green/Red

100 µL

RUO

KI-10611

Green/Red/Blue

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUND

The MET proto-oncogene is a receptor-like tyrosine kinase that drives aphysiological cellular program important for development, cell movement, cell
repair and cellular growth. Aberrant execution of this program has been associatedto neoplastic transformation, invasion and metastasis. Activation of MET has beenreported in a significant percentage of human cancers including non-small cell lungcancer (NSCLC) and is amplified during the transition between primary tumors andmetastasis.

Rearrangements of the protooncogene MYC (C-MYC) have been consistently foundin Burkitt’s lymphoma tumor cells. In cases with the common t(8;14) chromosomaltranslocation, the MYC gene is translocated to chromosome 14 and rearranged
with the immunoglobulin heavychain genes; the breakpoint occurs 5’ to the MYC
gene and may disrupt the gene itself. In Burkitt’s lymphoma showing the variantt(2;8) or t(8;22) translocations, the genes coding for the k and l immunoglobulin
light chain are translocated to chromosome 8. The rearrangement takes place 3’ tothe MYC gene.

The MET (7q31) FISH probe is optimized to detect copy numbers of the MET generegion at region 7q31. The Chromosome 7 Satellite enumeration probe (SE 7) at
D7Z1 is included to facilitate chromosome identification.

The MYC (8q24) Break probe is optimized to detect rearrangements involving the
8q24 locus in a triple-color, split assay on metaphase/ interphase spreads, bloodsmears and bone marrow cells.

REFERENCESREFERENCES

Go et al, 2010, J Thorac Oncol 5: 305-313.
Hara et al, 1998, Lab Invest 78; 1143-1153.
Tsugawa et al, 1998, Oncology 55; 475-481.

Fabris et al, 2003, Genes Chromosomes Cancer, 37;261-269.
Hummel et al, 2006, N Engl J Med, 354; 2419-30.

D8S1813880 kB
RH77966

D7Z1

D8S1128

MYC

D7S3086740 kB

SHGC-172475

7q31

MET

D8S1017450 kB

870 kB

8q24.2
SHGC-79904

8

RH75025

7* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

273

A

D

V

A

N

C

E

D

S

T

A

I

N

I

MYC (8q24) Break (tissue)

N

G

-

R

U

O

P

R

O

B

E

MYC / SE 8
Hybridization of MYC TC
break probe to a tissue
section showing“abarrant
pattern (1GBR1G1BR).

MYC (8q24) / SE 8 hybridized
to a metaphase spreadshowing a normal pattern.

MYC (8q24) Triple-Color, Break (tissue)

MYC (8q24) / SE 8

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10749

Green/Red/Blue

100 µL

RUO

KI-10106

Green/Red

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUND

Rearrangements of the proto oncogene MYC c-myc) have been consistently foundin Burkitt’s lymphoma tumor cells . In cases with the common t(8;14) chromosomaltranslocation, the MYC gene is translocated to chromosome 14 and rearranged
with the immunoglobulin heavy chain genes; the breakpoint occurs 5’ to the MYC
gene and may disrupt the gene itself. In Burkitt’s lymphoma showing the variantt(2;8) or t(8;22) translocations, the genes coding for the k and l immunoglobulin
light chain are translocated to v-myc avian myelocytomatosis viral oncogene
homolog (MYC or c-myc) chromosome 8.

The MYC (previously known as C-MYC) gene produces an oncogenic transcription
factor that affects diverse cellular processes involved in cell growth, cellproliferation, apoptosis and cellular metabolism. The MYC oncogene has beenshown to be amplified in many types of human cancer such as bladder, breastand cervical. Amplification at 8q24 including MYC is also observed in 5% of CLL
patients. MYC is also the prototype for oncogene activation by chromosomaltranslocation.
The MYC (8q24) specific FISH probe is optimized to detect copy numbers of the
MYC gene region at 8q24. The chromosome 8 Satellite Enumeration FISH probe(SE 8) at D8Z1 is included to facilitate chromosome identification.

The MYC (8q24) Break probe is optimized to detect rearrangements involving the
8q24 locus in a triple-color, split assay on formalin fixed paraffin embedded tissue.
REFERENCESREFERENCES

Fabris et al, 2003, Genes Chromosomes Cancer, 37;261-269.
Hummel et al, 2006, N Engl J Med, 354; 2419-30.

Greil et al, 1991, Blood, 78; 180-191.

D8S1813D8Z1

880 kB

SHGC-140056

MYC

RH77966
D8S1128

MYC

SHGC-144185

D8S10178

215 kB

740 kB

SHGC-172475

8q24.2870 kB

8q24.2S

8

RH75025* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

274

A

D

V

A

N

C

E

D

S

T

A

I

N

I

MYC / IGH t(8;14) Fusion

N

G

-

R

U

O

P

R

O

B

E

MYCN / AFF3
Hybridization of MYC/IGH
fusion probe to a metaphasespread showing normal
pattern (2R2G).

MYCN (2p24) / AFF3 (2q11)
hybridized to a cell line
showing amplification of
MYCN on chromosome 13
and 15.

Image kindly provided by
Pasteur Workshop 2008,
Paris.

MYC / IGH t(8;14) Fusion

MYCN (2p24) / AFF3 (2q11)

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10603

Green/Red

100 µL

RUO

KI-10706

Green/Red

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUND

The translocation t(8;14)(q24;q32) is the characteristic chromosomal aberrationof Burkitt’s-type of lymphomas. This translocation fuses the MYC gene at 8q24
next to the IGH locus at 14q32, resulting in overexpression of the transcription
factor MYC. Detection of the t(8;14) is aimed to help in the diagnostic process ofpatients with high-grade B-cell lymphomas because treatment strategies differ
between Burkitt and other high-grade lymphomas. The MYC / IGH t(8;14)(q24;q32)
specific FISH probe is optimized to detect the reciprocal translocation t(8;14) in adual-color, dual-fusion assay.

Amplification of the human protooncogene, v-myc avian myelocytomatosis viraloncogene neuroblastoma derived homolog (MYCN) is frequently seen either
in extrachromosomal double minutes or in homogeneously staining regions of
aggressively growing neuroblastomas. MYCN amplification has been defined by
the INRG as > 4-fold MYCN signals compared to 2q reference probe signals.
The MYCN (2p24) FISH probe is optimized to detect copy numbers of the MYCN
gene region at 2p24. The AFF3 gene region probe at 2q11 is included to facilitate
chromosome identification.

REFERENCESREFERENCES

Veronese et al, 1995, Blood, 85;2132-2138.
Siebert et al, 1998, Blood, 91; 984-990.

Shapiro et al, 1993, Am J Pathol, 142: 1339-1346.
Corvi et al, 1994, PNAS, 91: 5523-5527.

RH40515

D14S683E

2p24

RH67659

MYCN

MYC

IGH

1270 kB

670 kB

1420 kB
RH30315

14q32
8q24.2814RH66790

2q11.2

SHGC-84336

SHGC-172475

AFF3

375 kB

RH670982* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

275

S

A

D

V

A

N

C

E

D

S

T

A

I

N

I

MYEOV / IGH

N

G

-

R

U

O

P

R

O

B

E

“N25” / SHANK3MYEOV / IGH t(11;14) Fusion
probe hybridized to MM
patient material showingt(11;14) translocation(2RG1R1G).

DiGeorge “N25” (22q11)/ 22q13 (SHANK3) probehybridized to a normal
metaphase (2R2G).

Image kindly provided by
Prof. Jauch, Heidelberg.

MYEOV / IGH t(11;14) Fusion“N25” (22q11) / 22q13 (SHANK3)

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10605

Green/Red

100 µL

RUO

KI-40102

Green/Red

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUND

The most common chromosomal translocation in multiple myeloma (MM)is t(11;14), resulting in up-regulation of cyclin D1. In MM the breakpoints arescattered within a 360-kb region between CCND1 and MYEOV. This breakpoint ismore proximal than the t(11;14) breakpoints observed in mantle cell lymphoma orother leukemias. Patients with MM who have t(11;14)(q13;q32) seem to have an
aggressive clinical course.

The DiGeorge “N25” FISH probe was the first commercial microdeletion probe forchromosome 22q and detects the locus D22S75. This marker is located between
DGCR2 and CLTCL1 (Clathrin). Both genes have been extensively investigated andtheir role in DiGeorge syndrome is well established.
The DiGeorge “N25” region probe covers the marker “N25” (D22S75) and adjacentregion of CLTCL1 (Clathrin gene region) and DGCR2 (DiGeorge critical region gene2). The SHANK3 FISH probe at 22q13 is serving as internal control.

The MYEOV / IGH t(11;14)(q13;q32) Fusion specific FISH probe is optimized todetect the reciprocal translocation t(11;14) in a dual-color, dual-fusion assay.

REFERENCESREFERENCES

Sirotkin et al, 1996, Hum. Mol. Genet., 5; 617-624.
Holmes et al, 1997, Hum. Mol. Genet., 6; 357-367.
Wilson, et al, 2003, J. Med. Genet., 40; 575-584.
Luciani, et al, 2003, J. Med. Genet., 40; 690-696.

Janssen et al., 2000, Blood, 95; 2691-2698.
Fonseca et al, 2002, Blood, 99; 3735-3741.

D11S1138
D14S683E

510 kB

D22S1660

RH69373

DGCR2

MYEOV

IGH

11q13

1420 kB

"N25"

CCND1
RH67810

FGF4
FGF3

11

315 kB

CLTCL1
14q32

550 kB

14

D22S1646

RH66790

22q11.2

D22S553

RH48109

22

HIRA
22q13
RH8457

ARSA
130 kBSHANK3
RH38881* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

276

S

A

D

V

A

N

C

E

D

S

T

A

I

N

I

NF1 / MPO

N

G

-

R

U

O

P

R

O

B

E

S

NSD1 / TERTNF1 (17q11) / MPO (17q22)
probe hybridized to patientmaterial showing a deletionof NF1 gene region at 17q11(1R2G).

NSD1 (5q35) / TERT (5p15)
probe hybridized to a normal
metaphase (2R2G).

NF1 (17q11) / MPO (17q22)

NSD1 (5q35) / TERT (5p15)

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-40114

Green/Red

100 µL

RUO

KI-40113

Green/Red

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUND

NF1, or Von Recklinghausen disease, is one of the most common hereditaryneurocutaneous disorders in humans and one of the most common single gene
syndromes. Clinically, NF1 is characterized by café-au-lait spots, freckling, skinneurofibroma, plexiform neurofibroma, bone defects, Lisch nodules and tumorsof the central nervous system. The responsible gene, NF1 (neurofibromin), wasidentified on chromosome 17q11. Whole NF1 gene deletions occur in 4%-5% of
individuals with NF1 and can be detected by FISH analysis.

NSD1 microdeletions (chromosome 5q35) are the major cause of Sotos syndrome,and occur in some cases of Weaver syndrome. Sotos is a childhood overgrowth
characterized by distinctive craniofacial features, advanced bone age, and mental
retardation. Weaver syndrome is characterized by the same criteria but has its
own specific facial characteristics. Sotos syndrome is inherited in an autosomal
dominant manner. While 50% of Sotos patients in Asia are showing a chromosomal
microdeletion, only 9% deletion cases are observed in the affected European
population.

The NF1 (17q11) region probe is optimized to detect copy numbers of the NF1gene region at 17q11.2. The MPO region specific FISH probe at 17q22 is included
as control probe.

The NSD1 (5q35) region probe is optimized to detect copy numbers of the NSD1
gene region at 5q35.2. The TERT region specific FISH probe at 5p15 is included ascontrol probe.

REFERENCESREFERENCES

Riva P et al, 2000, Am. J. Hum. Genet., 66; 100-109.
Dorschner et al, 2000, Hum. Mol. Genet., 9; 35-46.

Douglas et al, 2003, Am. J. Hum. Genet. 72; 132-143.
Rio et al, 2003, J. Med. Genet., 40; 436-440.

D17S1307

NF1

5p15.3
SHGC-154319

420 kBTERT390 kB

RH25868
17q11

D5S2269E
SHGC-16044

17q22

17

MPO

D5S2703

500 kB

NSD1

SHGC-144222
5q35

5330 kB

RH10047* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

277

A

D

V

A

N

C

E

D

S

T

A

I

N

I

NUP98 Break

N

G

-

R

U

O

P

R

O

B

E

S

PAFAH1B1 / 17p11
NUP98 (11p15) Break
Probe hybridized to AML
patient sample showing arearrangement of 11p15
involving the NUP98 gene
(1F1R1G).

Miller-Dieker PAFAH1B1(17p13)/ Smith-Magenis
RAI1 (17p11) probehybridized to a normal
metaphase (2RG).

Image kindly provided by
Prof. Manuel R. Teixeira,Porto.

NUP98 (11p15) Break

PAFAH1B1 (17p13) / RAI1 (17p11)

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10311

Green/Red

100 µL

RUO

KI-40101

Green/Red

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUND

Nucleoporin 98kDa gene (NUP98) rearrangements have been identified in a wide
range of hematologic malignancies, including acute myeloid leukemia (AML), acutelymphoblastic leukemia (ALL), chronic myeloid leukemia in blast crisis (CML-bc),
myelodysplastic syndrome (MDS) and bilineage/biphenotypic leukemia. The
NUP98 gene is highly promiscuous with regard to its recombination spectrum, as
at least 28 different partner genes have been identified for NUP98 rearrangements,
all forming in-frame fusion genes. Patients with NUP98 gene rearrangements havean aggressive clinical course and the outcome of treatment is disappointing.

The Miller-Dieker lissencephaly syndrome appears to be caused by deletion ofseveral genes on 17p including the PAFAH1B1 (previously known as LIS1) gene.

The NUP98 (11p15) Break FISH Probe is optimized to detect translocations
involving the NUP98 gene region at 11p15 in a dual-color assay on metaphase/interphase spreads, blood smears and bone marrow cells.

The Miller-Dieker PAFAH1B1 region probe is optimized to detect copy numbers of
the PAFAH1B1 region at 17p13. The Smith-Magenis RAI1 region probe is optimized
to detect copy numbers of the RAI1 gene region at 17p11.

About 15% of patients with isolated lissencephaly and more than 90% of patientswith Miller-Dieker syndrome have microdeletions in a critical 350-kb region at
17p13.3. Smith-Magenis is caused by a deletion of 17p11.2. The RAI1 (previously
known as SMCR, KIAA1820 or SMS) gene region has been identified to be deleted
in more than 90% of Smith-Magenis syndrome patients.

REFERENCESREFERENCES

Gough et al, 2011, Blood, 118; 62 47-6257.
Nebral et al, 2005, Haematologica, 90; 74 6-752.
Romana et al, 2006, Leukemia, 20; 696-70 6.

Kuwano et al, 1991, Am. J. Hum. Genet., 49; 707-714.
Cardoso et al, 2003, Am. J. Hum. Genet., 72; 918-930.
Smith et al, 1986, Am. J. Med. Genet., 24; 393-414.
Greenberg et al, 1991, Am. J. Med. Genet., 49; 1207-1218.
Vlangos et al, 2005, Am. J. Med. Genet., 132; 278-282.

SHGC-84145
11p15

530 kB
RH75370

NUP98

SHGC-5886

GAP 455 kB

17p13

PAFAH1B1

D11S4525

410 kB

350 kB

D17S1566

SHGC-79113
17p11.2

11

17

UT159

RAI1
240 kB
RH68538* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

278

A

D

V

A

N

C

E

D

S

T

A

I

N

I

PDGFRB Break

N

G

-

R

U

O

P

R

O

B

E

S

PML / RARAPDGFRB (5q32) Break probehybridized to a normal
metaphase (2RG).

PML / RARA t(15;17) Fusion
probe hybridized to a normal
metaphase (2R2G).

PDGFRB (5q32) BreakPML / RARA t(15;17) Fusion

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10004

Green/Red

100 µL

RUO

KI-10302

Green/Red

100 µL

RUO

KI-12302

Green/Red

200 µLRUO

MENURESEARCHMENU
RESEARCH

BACKGROUNDBACKGROUNDPDGFRB activation has been observed in patients with chronic myelomonocytic
leukemia/atypical chronic myeloid leukemia and has been associated with over
50“translocation partners, the best known is the ETV6 gene on 12p13, causing at(5;12) translocation. Cytogenetic responses are achieved with imatinib in patientswith PDGFRB fusion positive, BCR / ABL1 negative CMPDs.

REFERENCES

A structural rearrangement involving chromosomes 15 and 17 in acutepromyelocytic leukemia (APL) was first recognized in 1977. The critical junction is
located on the der(15) chromosome and consists of the 5’ portion of PML fused
to virtually all of the RARA gene. The PML / RARA fusion protein interacts with acomplex of molecules known as nuclear co-repressors and histone deacetylase.
This complex binds to the fusion protein and blocks the transcription of target
genes. Other less common variant translocations fuse the RARA gene on 17q21 to
the PLZF, NPM, NUMA, and STAT5b genes, respectively.

Wlodarska et al, 1997, Blood, 89; 1716-1722.
Wilkinson et al, 2003, Blood, 102; 4287-419.

The PML / RARA t(15;17) Fusion specific FISH probe is optimized to detect thereciprocal translocation t(15;17) (q24;q21) in a dual-color, dual-fusion assay.

The PDGFRB (5q32) Break FISH probe is optimized to detect translocations
involving the PDGFRB region at 5q32 in a dual-color, split assay.

REFERENCES
Schad et al, 1994, Mayo Clin Proc, 69; 1047-1053.
Brockman et al, 2003, Cancer Genet Cytogenet, 145; 144-151.

D5S1907

340 kB
RH58356
SHGC-149501

PDGFRB

SHGC-156300

RH70663PML

410 kB

715 kB

17q21

RARA

5q32
D5S2014

15q24

5

15

SHGC-148679

17

RH69878* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

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450 kB

A

D

V

A

N

C

E

D

S

T

A

I

N

I

PPARG Break

N

G

-

R

U

O

P

R

O

B

E

S

PTEN / SE 10
PPARG (3p25) Break probehybridized to patient material
showing a translocation at
3p25 (1RG1R1G).

PTEN (10q23) / SE 10 probehybridized to prostate cancermaterial showing deletion of
PTEN gene region at 10q23(1R2G).

Image kindly provided by Dr.
Valent, Paris.

Image kindly provided by
Portuguese Cancer Inst.,
Porto.

PPARG (3p25) BreakPTEN (10q23) / SE 10

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10707

Green/Red

100 µL

RUO

KI-10718

Green/Red

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUND

Follicular thyroid carcinoma is associated with the chromosomal translocationt(2;3)(q13;p25), fusing PAX8 (2q13) with the nuclear receptor, peroxisome
proliferator-activated receptor Γ (PPARG). PPARG is located in a breakpoint
hot spot region, leading to recurrent alterations of this gene in thyroid tumorsof follicular origin including carcinomas as well as adenomas with or without
involvement of PAX8.

The gene ‘phosphatase and tensin homolog’ (PTEN), is a tumor suppressor locatedat chromosome region 10q23, that plays an essential role in the maintenanceof chromosomal stability, cell survival and proliferation. Loss of PTEN has beenfound in a wide number of tumors, and its important role is demonstrated by thefact that it is the second most frequently mutated gene after TP53. Loss of PTEN
significantly correlates with the advanced forms of gliomas, but also of prostatecancer and breast tumors.

A break or split probe for PPARG is best used to analyze translocation of the
PPARG (3p25) gene on formalin fixed paraffin embedded tissue for routine clinicaldiagnosis.

The PTEN (10q23) FISH probe is optimized to detect copy numbers of the PTEN
gene region at region 10q23. The Chromosome 10 Satellite enumeration probe (SE10) at D10Z1 is included to facilitate chromosome identification.

The PPARG (3p25) Break probe is optimized to detect translocations andamplification involving the PPARG gene region at 3p25 in a dual_color, split assay.

REFERENCES
Cairns et al, 1997, Cancer Res, 57 ; 4997-5000.
Hermans et al, 2004, Genes Chrom Cancer, 39; 171-184.

REFERENCES
French et al, 2003, Am J Pathol, 162; 1053-1060.
Drieschner et al, 2006, Thyroid, 16; 1091-1096.

RH113215
3p25

D3S1351325 kB

D10Z1

RH11148

480 kB

PPARG

RH47435
10q23

350 kB
D3S656PTEN

SHGC-143153

10

3* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

280

A

D

V

A

N

C

E

D

S

T

A

I

N

I

RARA Break

N

G

-

R

U

O

P

R

O

B

E

S

RB1 / RCAN1
RARA (17q21) Break probehybridized to patient material
showing a translocation at
17q21 (1RG1R1G).

RB1 (13q14)/RCAN1 (21q22)
probe hybridized to a normalinterphase (2R2G).

RARA (17q21) BreakRB1 (13q14) / RCAN1 (21q22)

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10305

Green/Red

100 µL

RUO

KI-40003

Green/Red

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUNDThis break apart probe can detect the numerous types of recurrent rearrangementof the RAR_ (Retinoid acid receptor, alpha) gene with various gene partners(e.g., PML, NPM, MLL, FIP1L1, NuMA1, PLZF, amongst the others), leading to
the formation of different reciprocal fusion proteins. The importance of retinoid
metabolism in acute promyelocytic leukemia (APL) is highlighted by the numerous
recent studies, but the different leukemogenic functions of the RARA fusion
proteins in the neoplastic myeloid development still has to be defined, as well as
the distinct clinical outcome of the patients with the variant forms of APL.

Trisomy 21 is one of the most common chromosomal abnormalities in live bornchildren and causes Down syndrome. Molecular analysis has revealed thatthe 21q22.1-q22.3 region appears to contain the gene(s) responsible for thecongenital heart disease observed in Down syndrome. Trisomy 13, also called
Patau syndrome, is a chromosomal condition that is associated with severe
mental retardation and certain physical abnormalities. The critical region has beenreported to include 13q14-13q32 with variable expression, gene interactions,orinterchromosomal effects. The RCAN1 (21q22) specific FISH probe is optimized
to detect copy numbers of chromosome 21 at 21q22 on uncultured amniotic cells.
The RB1 (13q14) specific FISH probe is optimized to detect copy numbers ofchromosome 13 at 13q14 on uncultured amniotic cells.

REFERENCES
Grimwade et al, 2000, Blood 96; 1297-1308

D21S1705

D13S1195
RH69066

530 kB
RH54996
17q21

13q14

RARA

RB1

21

RH17717610 kB17

21q22

910 kB

RCAN1
RH92717

D13S740

D17S1196

13* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

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650 kB

A

D

V

A

N

C

E

D

S

T

A

I

N

I

RB1 / RCAN1, SE X/SE Y/ SE 18

N

G

-

R

U

O

P

R

O

B

E

RCAN1 / SE X / SE Y
Hybridization of the RCAN1(21q22), SE X, SE Y probe toa male metaphase spreadshowing“normal pattern(2R1G1B).

RB1 (13q14) / RCAN1 (21q22), SE X (DXZ1) / SE Y (DYZ3) / SE
18 (D18Z1)
CODE

COLOR

FORMATSTATUS

KI-40005

Green/Red/Blue

100 µL

RUO

KI-40006

Green/Red/Blue

300 µL

RUO

KI-40007Green/Red/Blue

500 µL

RUO

MENU

-

RESEARCH

RCAN1 (21q22), SE X, YBACKGROUND
Trisomy 21 is one of the most common chromosomal abnormalities in live bornchildren and causes Down syndrome.

CODE

COLOR

FORMATSTATUS

KI-40008

Green/Red/Blue

200 µL

RUO

MENU

Trisomy 13, also called Patau syndrome, is a chromosomal condition that is
associated with severe mental retardation and certain physical abnormalities.
Trisomy 18 causing Edwards syndrome is the second most common autosomal
trisomy after trisomy 21. The disorder/condition is characterized by severe
symptoms. Turner syndrome occurs when females inherit only one X chromosome;their genotype is X0. Metafemales or triple-X females, inherit three X of
more chromosomes. Klinefelter syndrome males inherit one or more extra X
chromosomes; XYY syndrome males inherit an extra Y chromosome.

RESEARCH
BACKGROUNDREFERENCES

Chromosomal abnormalities involving the X and Y chromosome (sexchromosomes) are slightly less common than autosomal abnormalities andare usually much less severe in their effects. The high frequency of people with
sex chromosome aberrations is partly due to the fact that they are rarely lethal
conditions.

Uchida et al, 2010, Cancer Genet Cytogenet, 203; 324-327.
Sen et al, 2002, J of Nat Canc Inst, 94; 1320-1329.
Lassmann et al, 2007, Clin Cancer Res, 13; 4083-4091.

- Turner syndrome occurs when females inherit only one X chromosome - their
genotype is X0.
- Metafemales or triple-X females, inherit three X chromosomes - their genotype is
XXX or more rarely XXXX or XXXXX.

D21S1705

D13S1195

13q14

S

RB1

21q22

910 kB

21

RCAN1

650 kB- Klinefelter syndrome males inherit one or more extra X chromosomes - their
genotype is XXY or more rarely XXXY, XXXXY, or XY / XXY mosaic.

RH92717

D13S740
D21S1705

13
21q22

21

DYZ3

RCAN1

DYZ3
650 kB
DXZ1

RH92717

Y

D18Z1

DXZ1

Y

X

18

X

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

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A

D

V

A

N

C

E

D

S

T

A

I

N

I

RET Break

N

G

-

R

U

O

P

R

O

B

E

S

ROS1 BreakHybridization of RET breakprobe to a tissue section
showing“abarrant pattern(1RG1R1G).

Hybridization of ROS1 (6q22)
Break Probe (KBI-10752) toa tissue section harboring a
ROS1 rearrangement.

RET (10q11) BreakROS1 (6q22) Break

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10753

Green/Red

100 µL

RUO

KI-10752

Green/Red

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUND

Pericentric inversion of chromosome 10 involving the RET (ret proto-oncogene)
gene at chromosome 10q11 is known to increase expression of the RET gene byfusion with KIF5B (10p11). Translocations with other fusion partners have also
been described. Elevated expression of RET is observed in non-small cell lungcancer (NSCLC), in which the function of tyrosine kinase-based therapeutics isbased on the inhibition of such fusion proteins. Translocations involving RET havealso been described in thyroid carcinomas.

Translocations involving the ROS1 gene at chromosome 6q22 can increase
expression of the gene by fusion with SLC34A2 (4p15), but also with other fusion
partners. Elevated expression is observed in non-small cell lung cancer (NSCLC),
where the success of tyrosine kinase-based therapeutics like“Crizotinib (Xalkori)is based on inhibiting the activity of these fusion genes. The fusion of ROS1 to the
GOPC (FIG) gene, by deletion of a 240 kb DNA fragment, also results in activationof a fusion gene.

The RET (10q11) Break probe is optimized to detect translocations involving the
RET gene region at 10q11.

The ROS1 (6q22) Break probe is optimized to detect translocations involving
the ROS1 gene region at the 6q22 locus, as well as the 240 kb deletion forming
the ROS1-GOPC fusion gene, in a dual-color assay on formalin- fixed paraffinembedded tissue samples.

REFERENCES
Chen et al, Cancer Genet Cytogenet, 2007, 178: 128-134.
Kohno et al, Nat Med, 2012, 18: 375-377.
Takeuchi et al, Nat Med, 2012, 18: 378-381.

REFERENCES
Charest et al, Genes Chromosomes Cancer, 2003, 37: 58-71.
Rikova et al, Cell, 2007, 131: 1190-120.
Rimkunas et al, Clin. Can. Res., 2012, 18: 4449-4457.
Takeuchi et al, Nat. Med., 2012, 18: 378-381.
Gu et al, PLoS, 2011, 6: e15640.

RH51277535 kB
RET

10q11.2GDB:579598
D10S1176

500 kB
SHGC-14420
SHGC-148579

450 kB

10
RH69070

ROS1

RH104060

Exon 42
Exon 30

6q22

260 kB
RH68126GOPC

6* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

283

A

D

V

A

N

C

E

D

S

T

A

I

N

I

RUNX1 / RUNX1T1

N

G

-

R

U

O

P

R

O

B

E

S

SE 7 / SE 8
Hybridization of RUNX1/
RUNX1T1 fusion probe to a
metaphase spread showing
normal pattern (2R2G).

Hybridization of SE 7 / SE
8 probe to a metaphasespread showing normal
pattern (2R2G).

RUNX1 / RUNX1T1 t(8;21) Fusion

SE 7 (D7Z1) / SE 8 (D8Z1)

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10301

Green/Red

100 µL

RUO

KI-20031

Green/Red

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUNDt(8;21)(q21;q22) is the most frequently observed karyotypic abnormality
associated with acute myeloid leukemia (AML), especially in FAB M2. As aconsequence of the translocation the RUNX1 (previously known as AML) (CBFA2)
gene in the 21q22 region is fused to the RUNX1T1 (previously known as ETO)
(MTG8) gene in the 8q21 region, resulting in one transcriptionally active gene on
the 8q-derivative chromosome.

Trisomy 8 is found as one of the genetic changes in CML, while loss ofchromosome 7 is found in AML. The SE 7 (D7Z1) / SE 8 (D8Z1) FISH probes are
optimized to detect repetitive sequences located in the pericentric heterochromatinof chromosome 7 and 8.

The RUNX1 / RUNX1T1 t(8;21)(q21;q22) specific FISH probe is optimized to detect
the reciprocal translocation t(8;21) in a dual-color, dual-fusion assay.

D8Z1
D7Z1

REFERENCES
Sacchi et al, 1995, Genes Chrom Cancer, 79; 97-103.
Hagemeijer et al, 1998, Leukemia, 12; 96-101.

8
7

D21S325
SHGC-102339

RUNX1T1
(ETO)

21q22

1190 kB

21

8q21.3

RUNX1(AML1)

1380 kB

SHGC-9898

SHGC-1268

8* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

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A

D

V

A

N

C

E

D

S

T

A

I

N

I

SE X / SE Y

N

G

-

R

U

O

P

R

O

B

E

S

SE X / SE Y / SE 18
Hybridization of SE X / SE Y
probe to a male metaphasespread showing“normal
pattern (1R1G).

Hybridization of SE X / SE Y /SE 18 probe to a metaphasespread showing“normal
pattern (1R1G2B).

SE X (DXZ1) / SE Y (DYZ3)SE X (DXZ1) / SE Y (DYZ3) / SE 18 (D18Z1)

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-20030

Green/Red

100 µL

RUO

KI-20032

Green/Red/Blue

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUND

Chromosomal abnormalities involving the X and Y chromosome (sexchromosomes) are slightly less common than autosomal abnormalities andare usually much less severe in their effects. The high frequency of people with
sex chromosome aberrations is partly due to the fact that they are rarely lethal
conditions.

Chromosomal abnormalities involving the X and Y chromosome (sexchromosomes) are slightly less common than autosomal abnormalities andare usually much less severe in their effects. The high frequency of people with
sex chromosome aberrations is partly due to the fact that they are rarely lethal
conditions.

- Turner syndrome occurs when females inherit only one X chromosome - their
genotype is X0.

- Turner syndrome occurs when females inherit only one X chromosome - their
genotype is X0.

- Metafemales or triple-X females, inherit three X chromosomes - their genotype is
XXX or more rarely XXXX or XXXXX.

- Metafemales or triple-X females, inherit three X chromosomes - their genotype is
XXX or more rarely XXXX or XXXXX.

- Klinefelter syndrome males inherit one or more extra X chromosomes - their
genotype is XXY or more rarely XXXY, XXXXY, or XY / XXY mosaic.

- Klinefelter syndrome males inherit one or more extra X chromosomes - their
genotype is XXY or more rarely XXXY, XXXXY, or XY / XXY mosaic.

DYZ3

DYZ3

D18Z1

DXZ1

DXZ1

Y

Y

18

X

X

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

285

A

D

V

A

N

C

E

D

S

T

A

I

N

I

SHOX / SE X

N

G

-

R

U

O

P

R

O

B

E

SNRPN / PML
Short Stature SHOX (Xp22)/ SE X probe hybridized to amale metaphase (2R1G).

Prader-Willi SNRPN (15q11)/ PML (15q24) probehybridized to a normalinterphase/metaphase(2R2G).

SHOX (Xp22) / SE X

SNRPN (15q11) / PML (15q24)

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-40112

Green/Red

100 µL

RUO

KI-40109

Green/Red

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUND

Individuals with SHOX-related short stature have disproportionate short stature
and/or wrist abnormalities consistent with those described in Madelung deformity.
The SHOX genes located on the pseudoautosomal regions of the X and Y
chromosomes are the only genes known to be associated with SHOX-related
haploinsufficiency.

Prader-Willi Syndrome (PWS) is a clinically distinct disorder including
diminished fetal activity, obesity, hypotonia, mental retardation, short stature,hypogonadotropic hypogonadism, strabismus, and small hands and feet.
Approximately 70% of cases of PWS arise from paternal deletion of the 15q11-q13
region including the gene SNRPN (small nuclear ribonucleoprotein polypeptide N).
The PWS SNRPN region probe is optimized to detect copy numbers of the SNRPN
gene region at 15q11. The PML (promyelocytic leukemia) gene specific FISH probe
at 15q24 is included as control probe.

The SHOX region probe is optimized to detect copy numbers of the SHOX generegion at Xp22. The chromosome X Satellite Enumeration (SE X) FISH probe at
DXZ1 is added to facilitate chromosome identification.
REFERENCESREFERENCES

Rao et al, 1997, Hum. Genet., 100; 236-239.
Morizio et al, 2003, Am. J. Med. Genet., 119; 293-296.

Knoll et al, 1989, Am. J. Med. Genet., 32; 285-290.
Ozcelik et al, 1992, Nat. Genet., 2; 265-269.
D15S677

Xp22.3 / Yp11.3

SNRPN
DXYS153

DXZ1

Y

SHOX

S

220 kB

D15S631E
15q11.2

UBE3A

190 kBDXYS130

15q24

15

X

PML
SHGC-152035

180 kB
W1870* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

286

A

D

V

A

N

C

E

D

S

T

A

I

N

I

SRD / SE 1

N

G

-

R

U

O

P

R

O

B

E

S

SS18 BreakSRD (1p36) / SE 1 probehybridized to a normal
metaphase (2R2G).

SS18 (18q11) Break probehybridized to patient material
showing translocation of the
SYT (SS18) gene region at
18q11 (1RG1R1G).

SRD (1p36) / SE 1 (1qh)

SS18 (18q11) Break

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10712

Green/Red

100 µL

RUO

KI-10713

Green/Red

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUND

Neuroblastomas frequently have deletions of chromosome 1p and amplificationof the MYCN oncogene. These deletions tend to be large and extend to thetelomere, but a common region within sub-band 1p36.3 is consistently lost in thesedeletions. Inactivation of a tumor suppressor gene within 1p36.3 is believed to be
associated with an increased risk for disease relapse.

The characteristic chromosomal abnormality in Synovial Sarcoma t(X;18)(p11.2;q11.2) is present in 90% of the patients. This translocation results in thefusion of the synovial sarcoma translocation, chromosome 18 (SS18) gene toeither of two distinct genes, SSX1 or SSX2, located on the X chromosome.
The SS18 (18q11) Break probe is optimized to detect translocations involving the
SS18 gene region at 18q11 in a dual-color, split assay on paraffin embedded tissue
sections.

The SRD (1p36) FISH probe is optimized to detect copy numbers of the 1p36 region
on chromosome 1. The chromosome 1 satellite enumeration probe (SE 1) at 1qh is
included to facilitate chromosome identification.

REFERENCESREFERENCES

Kawai et al, 1998, NEJM, 338; 153-160.
Surace et al, 2004, LabInvest., 84; 1185-1192.

Caron et al, 1993, Nat Genet, 4: 187-190.
Cheng et al, 1995, Oncogene, 10: 291-297.
White et al, 2005, Oncogene, 24: 2684-2694.

SHGC-140887

1030 kB
18q11.2

1p36.3
SHGC-149299

SGC35446

SS18
RH79212690 kB

530 kB18

SHGC-84255

CHD5
SHGC-108153

1qh

1* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

287

A

D

V

A

N

C

E

D

S

T

A

I

N

I

STS / KAL1 / SE X

N

G

-

R

U

O

P

R

O

B

E

S

TBX1 / SHANK3
STS (Xp22) / KAL1 (Xp22)/ SE X Triple-Color probehybridized to male patientmaterial showing a deletionof the STS gene region(1R1B).

DiGeorge TBX1 (22q11)/ 22q13 (SHANK3) probehybridized to DiGeorge
patient material showing adeletion of the TBX1 generegion at 22q11 (1R2G).

Material kindly provided by
Necker hospital, Paris.

Image kindly provided by Dr.
F. Girard- Lemaire Service
de Cytogénétique (Dr. Flori),
CHU Strasbourg.

STS (Xp22) / KAL1 (Xp22) / SE X Triple-ColorTBX1 (22q11) / 22q13 (SHANK3)

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-40115

Green/Red/Blue

100 µL

RUO

KI-40104

Green/Red

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUND

STS (Steroid Sulfatase) disease is a chromosome X-linked disorder associatedwith a microdeletion of the gene within the Xp22.3 region. Deletion of the steroid
sulfatase gene has been detected in individuals with recessive X-linked ichtyosis,
the disease been considered one of the most frequent human enzyme deficientdisorders. KAL1 (Kallmann syndrome interval gene-1) maps to the Kallmann
syndrome critical region on the distal short arm of the human X chromosome.
Individuals with Kallmann syndrome suffers of hypogonadotropic hypogonadism
and anosmia, with clinical features of variable phenotype. It affects approximately
1 in 8000 males and 1 in 40000 females.

The 22q11 deletion in DiGeorge syndrome/VCFS is characterized by defects in thederivatives of the pharyngeal apparatus. TBX1, a member of the T-box transcription
factor family, is required for normal development of the pharyngeal arch arteries.
Haploinsufficiency of TBX1 has been demonstrated to be sufficient to generate atleast one important component of the DiGeorge syndrome phenotype in mice. The
TBX1 is also located within the minimal critical DiGeorge region in humans.
The DiGeorge TBX1 region probe is optimized to detect copy numbers of the TBX1
gene region at 22q11.2. The subtelomeric (ST) 22qter FISH probe is included ascontrol probe. The SHANK3 FISH probe at 22q13 is serving as internal control.

The STS (Xp22) region probe is optimized to detect copy numbers of the STS
gene region at Xp22. The KAL1 (Xp 22) region probe is optimized to detect
copy numbers of the KAL1 gene region at Xp22. The Chromosome X Satellite
Enumeration (SE X) FISH probe at DXZ1 is included to facilitate chromosome
identification.

REFERENCES
Lindsay et al, 2001, Nature, 410; 97-101.
Merscher et al, 2001, Cell, 104; 619-629.
Paylor et al, 2006, PNAS, 103; 7729-7734.

REFERENCES
Alper in et al, 1997, J. Biol. Chem., 272; 20756-20763.
Meroni et al, 1996, Hum. Mol. Genet., 5; 423-431.

Xp22.3

D22S1624

TBX1

DXS1130

STS

DXZ1

HIRA

RH47909

22

RH66689
Gap: 1 MB

22q13
RH8457ARSA

AFM309YC1

KAL1

230 kB

22q11.2

400 kB

130 kB
330 kBSHANK3
RH38881

DXS7716X* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

288

A

D

V

A

N

C

E

D

S

T

A

I

N

I

TERC / 3q11

N

G

-

R

U

O

P

R

O

B

E

S

TERC / MYC / SE 7
TERC (3q26) / 3q11 probehybridized to a normalinterphase/metaphase(2R2G).

TERC (3q26) / MYC (8q24)/ SE 7 Triple-Color probehybridized to a PAP smear(destained) showing 3q26
and 8q24 amplification. The
SE 7 control probe indicatesa non-triploid karyotype (2B).

Image kindly provided by Dr.
Weimer, Kiel.

TERC (3q26) / 3q11

TERC (3q26) / MYC (8q24) / SE 7 Triple-Color

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10110

Green/Red

100 µL

RUO

KI-10704

Green/Red/Blue

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUND

Amplification of the 3q26-q27 has a high prevalence in cervical, prostate, lung, andsquamous cell carcinoma. This amplification can also be found to a lesser extent
in CLL patients. The minimal region of amplification was refined to a 1- to 2-Mb
genomic segment containing several potential cancer genes including TERC, thehuman telomerase RNA gene.

The most consistent chromosomal gain in aneuploid tumors of cervical squamouscell carcinoma mapped to chromosome arm 3q, including the human telomerase
gene locus (TERC) at 3q26. Highlevel copy number increases were also mapped tochromosome 8. Integration of HPV (Human Papilloma Virus) DNA sequences into
MYC chromosomal regions have been repeatedly observed in cases of invasive
genital carcinomas and in cervical cancers.

The TERC (3q26) specific FISH probe is optimized to detect copy numbers of the
TERC (previously known as hTERC) gene region at region 3q26. The 3q11 region
probe is included to facilitate chromosome identification.

The TERC (3q26) FISH probe is optimized to detect copy numbers of the TERC
gene region at region 3q26. The MYC (8q24) FISH probe is optimized to detect
copy numbers of the MYC gene region at 8q24. The chromosome 7 satellite
enumeration probe (SE 7) at D7Z1 is included as ploidy control.

REFERENCES
Arnold et al, 1996, Genes Chrom Cancer, 16; 46-54.
Soder et al, 1997, Oncogene, 14; 1013-1021.

REFERENCES
Xie et al, 2008, Geburtshilfe Frauenheilkunde, 68: 573.
Heselmeyer et al, 1996, PNAS, 93: 479-484.
Herrick et al, 2005, Cancer Res, 65: 1174-1179.

SHGC-102405

640 kB

3q11.2

LINC00879
SHGC-141087
RH77966
RH17919540 kB590 kB

3q26.2

RH17919

MYC

TERC

3

590 kB

RH10606
3q26.2

8q24.2
SHGC-144185

8

TERC
RH10606

3

D7Z1

7

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
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289

A

D

V

A

N

C

E

D

S

T

A

I

N

I

TERT / 5q31

N

G

-

R

U

O

P

R

O

B

E

S

TERT / 5q31 (tissue)
TERT (5p15) / 5q31 probehybridized to a normalinterphase/metaphase(2R2G).

Hybridization of TERT / 5q31
Probe to a tissue section
showing“gain of the TERT
region.

Image kindly provided by Dr.
Mohr, Dresden.

TERT (5p15) / 5q31

TERT (5p15) / 5q31 (tissue)

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10208

Green/Red

100 µL

RUO

KI-10709

Green/Red

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUNDThe TERT / 5q31 dual-color FISH probe can be used to detect deletions involving
band 5q31 in MDS and RUNX1.

Amplifications of the TERT gene at 5p15 has been observed in a variety of cancers,
particularly lung cancer, cervical tumors, and breast carcinomas. Several studies
have revealed a high frequency of TERT gene amplification in human tumors,which indicates that the TERT gene may be a target for amplification during thetransformation of human malignancies and that this genetic event probably
contributes to a dysregulation of TERT/ telomerase occurring in a subset of humantumors.

The 5q- specific FISH probe is optimized to detect copy numbers at the CDC25C /EGR1 gene region at 5q31. The TERT (previously known as hTERT) gene region at
5p15 is included to facilitate chromosome identification.
REFERENCES

The TERT (5p15) FISH probe is designed as a dual-color assay to detect
amplification at 5p15. The CDC25C / EGR1 (5q31) gene region probe is included asinternal control.

Zhao et al, 1997, PNAS, 94; 6948-6053.
Horrigan et al, 2000, Blood, 95; 2372-2377.
5p15.3
SHGC-154319

TERT

REFERENCES
390 kB

Bryce et al, 2000, Neoplasia, 2;197-201.
Zhang et al, 2000, Cancer Res, 60;6230-6235

D5S2269E

5p15.3
SHGC-154319

RH48032

CDC25CTERT

650 kB

5q31

390 kB

D5S2269E

EGR1
SHGC-3896

5

RH48032

CDC25C
650 kB

5q31

EGR1
SHGC-3896

5* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
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290

A

D

V

A

N

C

E

D

S

T

A

I

N

I

TFE3 Break

N

G

-

R

U

O

P

R

O

B

E

S

TMPRSS2-ERG
TFE3 (Xp11) Break probehybridized to renal cell
carcinoma showing atranslocation at Xp11
(1RG1R1G).

TMPRSS2-ERG (21q22)
rearrangement probehybridized to prostate
carcinoma tissue showing
a deletion of the TMPRSS2(21q22) gene region
associated with TMPRSS2ERG fusion (1RGB 1RB).

Image kindly provided by Dr.
Desangles, Paris.

Image kindly provided by Dr.
Teixeira, Porto.

TFE3 (Xp11) BreakTMPRSS2-ERG (21q22) Deletion, Break, Triple-Color

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10741

Green/Red

100 µL

RUO

KI-10726

Green/Red/Blue

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUND

Abnormalities of Xp11.2 region have often been observed in papillary renal cell
carcinomas and are sometimes the sole cytogenetic abnormality present. The
transcription factor binding to IGHM enhancer 3 (TFE3) gene, which encodesa member of the helix-loop-helix family of transcription factors, is located inthis critical region and can be fused to various other chromosomal regions bytranslocation. Known fusion partners are NONO (Xq12), PRCC (1q21), SFPQ (1p34),
CLTC (17q23) and ASPSCR1 (17q25).

The transmembrane protease serine 2 gene (TMPRSS2) is involved in genefusions with ERG, ETV1 or ETV4 in prostate cancer. It has been reported that theexpression of the TMPRSS2-ERG fusion gene is a strong prognostic factor for therisk of prostate cancer recurrence in prostate cancer patients treated by surgery.
The TMPRSS2-ERG rearrangement probe is optimized to detect the deletion
between TMPRSS2 and ERG at 21q22 associated with the TMPRSS2-ERG fusion ina triple-color deletion assay.

The TFE3 (Xp11) Break probe is optimized to detect translocations involving theTFE3 gene region at Xp11.2 in a dual-color, break assay.

It also detects translocations involving the TMPRSS2 region such as ETV1 t(7;21),or ETV4 t(17;21).

REFERENCESREFERENCES

Sidhar et al, 1996, Hum Mol Genet, 5; 1333-1338.
Weterman et al, 1996, Proc Natl, Acad Sci, 93; 15294-15298.

Perner et al, 2006 Cancer Res 66; 8337-8341.
Hermans et al, 2006, Cancer Res 66; 10658-10663.
Attard et al, 2008, Oncogene 27; 253-263.

RH66279

530 kB
Xp11.2
RH18187

SHGC-85350

730 kB

TFE3
SHGC-106749

RH103001

ERG
ETS2

450 kBDXS1522

GAP 2.3 MB

D21S349X

21

630 kB

21q22
RH13802

TMPRSS2
SHGC-156046

700 kB
RH5200* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

291

A

D

V

A

N

C

E

D

S

T

A

I

N

I

TOP2A / ERBB2 / SE 17

N

G

-

R

U

O

P

R

O

B

E

S

TOP2A / SE 17
TOP2A (17q21) / ERBB2(17q12) / SE 17 TC probehybridized to breast tumor
tissue showing amplificationof TOP2A / ERBB2.

TOP2A (17q21) / SE 17
probe hybridized to breast
tissue (2R2G).

TOP2A (17q21) / ERBB2 (17q12) / SE 17, Triple-Color

TOP2A (17q21) / SE 17

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10735

Green/Red/Blue

100 µL

RUO

KI-10724

Green/Red

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUND

The presence of both TOP2A amplification and deletion in advanced cancer areassociated with decreased survival, and occur frequently and concurrently with
ERBB2 gene amplification (commonly refered to as HER2).

The Topoisomerase2A (TOP2A) enzyme, which is vital for the cell because of
its role in cell replication and repair, catalyzes the relaxation of supercoiled DNA
molecules to create a reversible double-strand DNA break. This enzyme is also thetarget of a number of cytotoxic agents, namely TOP2A inhibitors (anthracyclines,
etoposide, teniposide).

The TOP2A (17q21) / ERBB2 (17q12) / SE 17 probe is designed as a triple-color
assay to detect amplification at 17q12 as well as amplifications or deletions at
17q21. The chromosome 17 satellite enumeration probe (SE 17) at D17Z1 in blueis included to facilitate chromosome identification/enumeration.

The TOP2A (17q21) / SE 17 FISH probe is optimized to detect amplifications (copynumbers) or deletions of the TOP2A gene region at the 17q21. The chromosome
17 satellite enumeration probe (SE 17) at D17Z1 is included to facilitate
chromosome identification.

REFERENCES
Järvinen et al, 1999, Genes Chromosomes Cancer 26; 142-150.
Järvinen et al, 2000, Am. J. Pathology 156; 639-647.

REFERENCES
Järvinen et al, 1999, Genes Chromosomes Cancer 26; 142-150.
Järvinen et al, 2000, Am. J. Pathology 156; 639-647.

SHGC-85693

D17Z1

ERBB2

D17Z1

460 kB

RH54996

17q12
17q21

D17S1179
17q21
RH54996

17
TOP2A

17

370 kB
TOP2A
WI-9139370 kB

WI-9139* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

292

A

D

V

A

N

C

E

D

S

T

A

I

N

I

TP53 / ATM

N

G

-

R

U

O

P

R

O

B

E

S

TP53 / MPO
TP53 (17p13) / ATM (11q22)
hybridized to a normal
metaphase (2R2G).

TP53 (17p13) / MPO (17q22)“ISO 17q” probe hybridized
to peripheral blood ofa CLL patient with anisochromosome 17 (3R1G).

Image kindly provided by Dr.
Lana Harder, Kiel.

TP53 (17p13) / ATM (11q22)

TP53 (17p13) / MPO (17q22) “ISO 17q”

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10114

Green/Red

100 µL

RUO

KI-10011

Green/Red

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUND

Deletion of TP53 (previously known as p53) and ATM are both indicating poor
prognosis in CLL. Alterations of the TP53 (17p13) gene occur not only as somatic
mutations in human malignancies, but also as germline mutations in some cancerprone families with Li-Fraumeni syndrome. Deletions of TP53 are frequent in CLL
and MM, usually associated with unfavorable prognosis. Deletions of the long armof chromosome 11 (11q) are one of the most frequent structural chromosome
aberrations in various types of lymphoproliferative disorders. A critical genomic
region located in bands 11q22.3-q23.1 has been identified and contains among
other genes the ATM (ataxia telangiectasia mutated) gene.

Isochromosome 17q is the most common isochromosome in cancer. It plays animportant role in tumor development and progression. Hematologic malignancies
such as chronic myeloid leukemia (CML) with isochromosome 17q carry a poor
prognosis. Isochromosome 17q is the most common chromosome abnormality inprimitive neuroectodermal tumors and medulloblastoma. Isochromosome 17q is,by convention, symbolized as i(17q).

REFERENCES

The TP53 (17p13) / MPO (17q22) “ISO 17q” FISH probe is optimized to detect copy
numbers of the TP53 gene region at 17p13 and MPO gene region at 17q22. In caseof i(17q) a signal pattern of three red signals for MPO (17q22) and one signal for
TP53 at 17p13 is expected.

Boultwood J, 2001, J. Clin. Pathol., 54; 512-516
Amiel A et al, 1997, Cancer Gener.Cytogenet,, 97; 97-100
Drach J et al, 1998, Blood, 92; 802-809
Doehner H et al, 1997, Blood, 7; 2516-2522

Becher et al, 1990, Blood, 75; 1679-1683.
Fioretos et al, 1999, Blood, 94; 225-232.

REFERENCES

17p13

D17S960

D17S960

335 kB
17p13

335 kB

D11S4485

D17S634

TP53

RH55183

D17S634ATM
11q22

235 kB

TP53

17

17q22

MPO

500 kB

RH39918

17

11

SHGC-144222* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

293

A

D

V

A

N

C

E

D

S

T

A

I

N

I

TP53 / SE 17

N

G

-

R

U

O

P

R

O

B

E

S

TP53 / SE 17 (tissue)
TP53 (17p13) / SE 17 probehybridized to patient material
showing a 17p13 deletionat the TP53 gene region(1R2G).

Hybridization of TP53
probe to a tissue section
showing“normal pattern(2R2G).

TP53 (17p13) / SE 17 (tissue)

TP53 (17p13) / SE 17
CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-10112

Green/Red

100 µL

RUO

KI-10738

Green/Red

100 µL

RUO

KI-12112

Green/Red

200 µL

RUO

MENU
MENU

RESEARCHRESEARCH
BACKGROUNDBACKGROUNDThe TP53 tumor suppressor gene at 17p13, has been shown to be implicated in
the control of normal cellular proliferation, differentiation, and apoptosis. Allelicloss, usually by deletion, and inactivation of TP53 have been reported in numerous
tumor types and are associated with poor prognosis in CLL.

The TP53 tumor suppressor gene at 17p13, has been shown to be implicated in
the control of normal cellular proliferation, differentiation, and apoptosis. Allelicloss, usually by deletion, and inactivation of TP53 have been reported in numerous
tumor types and are associated with poor prognosis in CLL.

The TP53 (17p13) FISH probe is optimized to detect copy numbers of the TP53
gene region at 17p13. The chromosome 17 satellite enumeration probe (SE 17) at
D17Z1 is included to facilitate chromosome identification. Kreatech has developed
this probe for the specific use on cell material (KBI-10112 / KBI-12112), or for theuse on tissue (KBI-10738).

The TP53 (17p13) FISH probe is optimized to detect copy numbers of the TP53
gene region at 17p13. The chromosome 17 satellite enumeration probe (SE 17) at
D17Z1 is included to facilitate chromosome identification. Kreatech has developed
this probe for the specific use on cell material (KBI-10112 / KBI-12112), or for theuse on tissue (KBI-10738).

REFERENCES
Amiel A et al, 1997, Cancer Gener.Cytogenet,, 97; 97-100.
Drach J et al, 1998, Blood, 92; 802-809.

REFERENCES
Amiel A et al, 1997, Cancer Gener. Cytogenet, 97; 97-100.
Drach J et al, 1998, Blood, 92; 802-809.

17p13
D17S960
17p13
D17S960

D17Z1

D17Z1

335 kBTP53

335 kB

D17S634

TP53

17

D17S634

17* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

294

A

D

V

A

N

C

E

D

S

T

A

I

N

I

UBE3A / PML

N

G

-

R

U

O

P

R

O

B

E

S

WHSC1 / SE 4
Angelman UBE3A (15q11)/ PML (15q24) probehybridized to a normalinterphase/metaphase(2R2G).

Wolf-Hirschhorn WHSC1(4p16) / SE 4 probehybridized to WolfHirschhorn patient material
showing a deletion of the
WHSC1 gene region at 4p16
(1R2G).

Image kindly provided by
Prof. Zollino, Rome.

UBE3A (15q11) / PML (15q24)

WHSC1 (4p16) / SE 4

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-40110

Green/Red

100 µL

RUO

KI-40107

Green/Red

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUNDAngelman syndrome (AS) is characterized by severe developmental delay ormental retardation, severe speech impairment, gait ataxia and/or tremulousnessof the limbs, and an unique behavior with an inappropriate happy demeanor that
includes frequent laughing, smiling, and excitability. In addition, microcephaly andseizures are common. AS is caused by absence of a maternal contribution to theimprinted region on chromosome 15q11-q13 including the UBE3A gene.

Wolf-Hirschhorn Syndrome (WHS) affected individuals have prenatal-onset growth
deficiency followed by postnatal growth retardation and hypotonia with muscle
under-development. Developmental delay/mental retardation of variable degree ispresent in all. FISH analysis using a WHSC1 specific FISH probe for chromosomal
locus 4p16.3 detects more than 95% of deletions in WHS.
The Wolf-Hirschhorn region probe is optimized to detect copy numbers of the WolfHirschhorn critical region at 4p16. The chromosome 4 Satellite Enumeration (SE 4)
FISH probe at D4Z1 is included to facilitate chromosome identification.

The AS UBE3A region probe is optimized to detect copy numbers of the UBE3A
gene region at 15q11. The PML (promyelocytic leukemia) gene specific FISH probe
at 15q24 is included as control probe.

REFERENCESREFERENCES

Gandelman et al, 1992, Am. J. Hum. Genet., 51; 571-578.
Wright et al, 1997, Hum. Mol. Genet., 6; 317-324.

Matsuura et al, 1997, Nat. Genet., 15; 74-77.
Burger et al, 2002, Am. J. Med. Genet., 111; 233-237.

4p16

SNRPN

RH18137

D15S1089
15q11.2

UBE3A

120 kB

D4Z1
D4S114240 kB

WHSC1

D15S210

15q24

15

PML
SHGC-152035

180 kB

4

W1870* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

295

A

D

V

A

N

C

E

D

S

T

A

I

N

I

XIST / SE X

N

G

-

R

U

O

P

R

O

B

E

S

ZNF217 / 20q11
X-Inactivation XIST (Xq13)/ SE X probe hybridized to amale metaphase (1R1G).

ZNF217 (20q13) / 20q11
probe hybridized to tissue(2R2G).

XIST (Xq13) / SE X

ZNF217 (20q13) / 20q11

CODE

COLOR

FORMATSTATUS

CODE

COLOR

FORMATSTATUS

KI-40108

Green/Red

100 µL

RUO

KI-10733

Green/Red

100 µL

RUO

MENU

MENU

RESEARCHRESEARCH

BACKGROUNDBACKGROUNDThe XIST locus is expressed only from the inactive X chromosome, resides
at the putative X inactivation center, and is considered a prime player in theinitiation of mammalian X dosage compensation. The severe phenotype of human
females whose karyotype includes tiny ring X chromosomes has been attributed
to the inability of the small ring X chromosome to inactivate. Many of the ring
chromosomes lack the XIST locus, consistent with XIST being necessary for cis
inactivation.

Zinc-finger protein 217 (ZNF217) is a Kruppel-like zinc-finger protein locatedat 20q13.2, within a region of recurrent maximal amplification in a variety oftumor types, and especially breast cancer cell lines and primary breast tumors.
Copy number gains at 20q13 are also found in more than 25% of cancers of theovary, colon, head and neck, brain, and pancreas. ZNF217 is considered a strong
candidate oncogene that may have profound effects on cancer progression, which
is transcribed in multiple normal tissues, and overexpressed in almost all cell lines
and tumors in which it is amplified.

The XIST specific FISH probe is optimized to detect copy numbers of the XIST
region at Xq13. The chromosome X Satellite Enumeration (SE X) FISH probe at
DXZ1 is added to facilitate chromosome identification.

The ZNF217 (20q13) FISH probe is optimized to detect copy numbers of 20q at
20q13. The 20q11 probe is included to facilitate chromosome identification.

REFERENCESREFERENCES

Migeon et al, 1993, PNAS, 90; 12025-12029.
Jani et al, 1995, Genomics, 27; 182-188.

Tanner M et al, 2000, Clin Cancer Res, 6; 1833-1839.
Ginestier C et al, 2006, Clin Cancer Res, 12; 4533-4544.

SHGC-144070

DXZ1

MAPRE1610 kB

RH70575
Xq13

CHIC1

20q11.2

290 kB

20

RH57467

20q13.2
SHGC-80749

DXS8235X

XIST
ZNF217570 kB

SHGC-83153* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

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M
Product NameA

N

Product code

U

A

L

Color

F
Content

I

S

H

P

Conc

R

O

B

E

S

Product Name

(

A

S

R

Product code

)
Color

Content

Conc

13q34

13Q002B495

Green

50 µL

2x

IGH (14q32)-002

14Q002B550

Red

50 µL

2x

13q34

13Q002C415

Blue

33 µL

3x

JAK2 (9p24) Distal

09P004B550

Red

50 µL

2x

13q34

13Q002C495

Green

33 µL

3x

JAK2 (9p24) Proximal

09P003B495

Green

50 µL

2x

13q34

13Q002I495

Green250 µL

2x

MAF (16q23)

16Q001B495

Green

50 µL

2x

13q34

13Q002J415

Blue

166 µL

3x

MAF (16q23)

16Q001I495

Green250 µL2x

3q11

03Q002B495

Green

50 µL

2x

MAFB (20q12)

20Q002B495

Green

50 µL

2x

5q11.2 (ISL1)

05Q006B495

Green

50 µL

2x

MECOM (3q26) Distal-004

03Q004B550

Red

50 µL

2x

6q21

06Q001A550

Red

100 µLRtU

MECOM (3q26) Distal-004

03Q004C550

Red

33 µL

3x

ABL1 (9q34)

09Q001C415

Blue

33 µL

3x

MECOM (3q26) Distal-006

03Q006C415

Blue

33 µL

3x

ALK (2p23) Distal

02P002B550

Red

50 µL

2x

MECOM (3q26) Proximal

03Q003B495

Green

50 µL

2x

ALK (2p23) Distal-HS

02P006B550

Red

50 µL

2x

MECOM (3q26) Proximal-005

03Q005C495

Green

33 µL

3x

ALK (2p23) Proximal

02P001B495

Green

50 µL

2x

MET (7q31)

07Q001B550

Red

50 µL

2x

ALK (2p23) Proximal-HS

02P005B495

Green

50 µL

2x

PDGFRA (4q12)

04Q001B550

Red

50 µL

2x

ATM (11q22)

11Q001B495

Green

50 µL

2x

PDGFRA (4q12)-004

04Q004C415

Blue

33 µL

3x

ATM (11q22)

11Q001I495

Green250 µL

2x

PDGFRB (5q32) Distal

05Q001B495

Green

50 µL

2x

CCND1 (11q13)

11Q002B495

Green

50 µL

2x

PDGFRB (5q32) Proximal

05Q002B550

Red

50 µL

2x

CCND1 (11q13)

11Q002I495

Green250 µL

2x

PTEN (10q23)

10Q006B550

Red

50 µL

2x

CCND3 (6p21)

06P003B495

Green

50 µL

2x

RET (10q11) Distal

10Q001B495

Green

50 µL

2x

CHIC2 (4q12)

04Q003C550

Red

33 µL

3x

RET (10q11) Proximal

10Q002B550

Red

50 µL

2x

CKS1B (1q21)

01Q001B495

Green

50 µL

2x

ROS1 (6q22) Distal

06Q002B495

Green

50 µL

2x

CKS1B (1q21)

01Q001B550

Red

50 µL

2x

ROS1 (6q22) Distal-SV

06Q005B550

Red

50 µL

2x

CKS1B (1q21)

01Q001I550

Red250 µL

2x

ROS1 (6q22) Proximal

06Q003B495

Green

50 µL

2x

CKS1B (1q21)

01Q001N550

Red

50 µL

10x

ROS1 (6q22) Proximal

06Q003B550

Red

50 µL

2x

CRLF2 (Xp22/Yp11)

23P004C550

Red

33 µL

3x

RREB1 (6p24)

06P001D590

Red

25 µL

4x

CRLF2 (Xp22/Yp11) Distal

23P003C495

Green

33 µL

3x

SE 10 (D10Z1)

10C001B495

Green

50 µL

2x

CRLF2 (Xp22/Yp11) Proximal

23P002C550

Red

33 µL

3x

SE 10 (D10Z1)

10C001N495

Green

50 µL

10x

DLEU1 (13q14)

13Q001B550

Red

50 µL

2x

SE 12 (D12Z3)

12C001C495

Green

33 µL

3x

DLEU1 (13q14)

13Q001C415

Blue

33 µL

3x

SE 12 (D12Z3)

12C001J495

Green

166 µL

3x

DLEU1 (13q14)

13Q001C550

Red

33 µL

3x

SE 17 (D17Z1)-006

17C006B495

Green

50 µL

2x

DLEU1 (13q14)

13Q001I550

Red250 µL2x

SE 3 (D3Z1)

03C001C550

Red

33 µL

3x

DLEU1 (13q14)-SV

13Q003C550

Red

33 µL

3x

SE 3 (D3Z1)

03C001N415

Blue

50 µL

10x

DLEU1 (13q14)-SV

13Q003J550

Red

166 µL3x

SE 4 (D4Z1)

04C001B495

Green

50 µL

2x

EGFR (7p11)

07P001B550

Red

50 µL

2x

SE 6 (D6Z1)

06C001D415

Blue

25 µL

4x

EGFR (7p11)

07P001C495

Green

33 µL

3x

SE 7 (D7Z1)

07C001B495

Green

50 µL

2x

ERBB2 (17q12)

17Q002B550

Red

50 µL

2x

SE 7 (D7Z1)

07C001C495

Green

33 µL

3x

FGFR1 (8p11)

08P003B550

Red

50 µL

2x

SE 7 (D7Z1)-002

07C002B495

Green

50 µL

2x

FGFR1 (8p11) Distal

08P002B550

Red

50 µL

2x

SE 8 (D8Z1)

08C001B495

Green

50 µL

2x

FGFR1 (8p11) Proximal

08P001B495

Green

50 µL

2x

SE 8 (D8Z1)-002

08C002B495

Green

50 µL

2x

FGFR2 (10q26)

10Q003B550

Red

50 µL

2x

SE X (DXZ1)

23C001B495

Green

50 µL

2x

FGFR2 (10q26) Distal

10Q004B550

Red

50 µL

2x

SE X (DXZ1)

23C002J495

Green

166 µL

3x

FGFR2 (10q26) Proximal

10Q005B495

Green

50 µL

2x

SHOX (Xp22)

23P001B550

Red

50 µL

2x

FGFR3 (4p16)

04P001B495

Green

50 µL

2x

SRD (1p36)

01P001B495

Green

50 µL

2x

FGFR3 (4p16)

04P001I495

Green250 µL

2x

SRD (1p36)

01P001I495

Green250 µL

2x

FGFR3 (4p16) Distal

04P003B495

Green

50 µL

2x

SRD (1p36)

01P001N495

Green

50 µL

10x

FGFR3 (4p16) Proximal

04P002B550

Red

50 µL

2x

TERC (3q26)

03Q001B550

Red

50 µL

2x

FGFR4 (5q35)

05Q005B550

Red

50 µL

2x

TOP2A (17q21)

17Q003B550

Red

50 µL

2x

FIP1L1 (4q12)

04Q002C495

Green

33 µL

3x

TP53 (17p13)

17P001B550

Red

50 µL

2x

IGH (14q32)

14Q001B550

Red

50 µL

2x

TP53 (17p13)

17P001C550

Red

33 µL

3x

IGH (14q32)

14Q001I550

Red250 µL

2x

TP53 (17p13)

17P001I550

Red250 µL

2x* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

297

X
Product Name

Product code

L

F
Color

I

S

H

P

Content

Conc

ALK (2p23) Proximal - XL

02P008V495

Green

1 mL

10x

ALK (2p23) Distal - XL

02P009V550

Red

1 mL

10x

BCL6 (3q27) Proximal - XL

03Q009V495

Green

1 mL

10x

BCL6 (3q27) Distal - XL

03Q010V550

Red

1 mL

10x

ROS1 (6q22) Proximal - XL

06Q006V495

Green

1 mL

10x

ROS1(6q22) Distal - XL

06Q007V550

Red

1 mL

10x

SE 7 (D7Z1)-006 - XL

07C006V495

Green

1 mL

10x

MET (7q31) - XL

07Q002V550

Red

1 mL

10x

SE 8 (D8Z1)-003 - XL

08C003V495

Green

1 mL

10x

FGFR1 (8p11) - XL

08P004V550

Red

1 mL

10x

MYC (8q24) Proximal - XL

08Q007V495

Green

1 mL

10x

MYC (8q24) Distal - XL

08Q008V550

Red

1 mL

10x

RET (10q11) Distal - XL

10Q007V495

Green

1 mL

10x

RET (10q11) Proximal - XL

10Q008V550

Red

1 mL

10x

IGH (14q32) Proximal - XL

14Q004V550

Red

1 mL

10x

IGH (14q32) Distal - XL

14Q005V495

Green

1 mL

10x

TP53 (17p13) - XL

17P002V550

Red

1 mL

10x

BCL2 (18q21) Proximal - XL

18Q003V495

Green

1 mL

10x

BCL2 (18q21) Distal - XL

18Q004V550

Red

1 mL

10x

ERBB2 (17q12) - XL

17Q004V550

Red

1 mL

10x

SE 17 (D17Z1)-007 - XL

17C007V495

Green

1 mL

10x

R

O

B

E

S

(

A

S

R

)

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

298

S

A T

E

L

Product Name

L

I

T

E

E

Product code

N

U

M

Color

E

R

A T

Content

Conc

I

O

N

F

I

S

H

Product Name

P

R

O

B

Product code

E

S

(

A

Color

Content

S

R
Conc

SE 1 (1qh) Blue

KI-20001B

Blue

20 µL

5x

SE 11 (D11Z1) Red

KI-20011R

Red

20 µL

5x

SE 1 (1qh) Green

KI-20001G

Green

20 µL

5x

SE 12 (D12Z3) Blue

KI-20012B

Blue

20 µL

5x

SE 1 (1qh) Red

KI-20001R

Red

20 µL

5x

SE 12 (D12Z3) Green

KI-20012G

Green

20 µL

5x

SE 2 (D2Z) Blue

KI-20002B

Blue

20 µL

5x

SE 12 (D12Z3) Red

KI-20012R

Red

20 µL

5x

SE 2 (D2Z) Green

KI-20002G

Green

20 µL

5x

SE 15 (D15Z) Blue

KI-20015B

Blue

20 µL

5x

SE 2 (D2Z) Red

KI-20002R

Red

20 µL

5x

SE 15 (D15Z) Green

KI-20015G

Green

20 µL

5x

SE 3 (D3Z1) Blue

KI-20003B

Blue

20 µL

5x

SE 15 (D15Z) Red

KI-20015R

Red

20 µL

5x

SE 3 (D3Z1) Green

KI-20003G

Green

20 µL

5x

SE 16 (D16Z2) Blue

KI-20016B

Blue

20 µL

5x

SE 3 (D3Z1) Red

KI-20003R

Red

20 µL

5x

SE 16 (D16Z2) Green

KI-20016G

Green

20 µL

5x

SE 4 (D4Z1) Blue

KI-20004B

Blue

20 µL

5x

SE 16 (D16Z2) Red

KI-20016R

Red

20 µL

5x

SE 4 (D4Z1) Green

KI-20004G

Green

20 µL

5x

SE 17 (D17Z1) Blue

KI-20017B

Blue

20 µL

5x

SE 4 (D4Z1) Red

KI-20004R

Red

20 µL

5x

SE 17 (D17Z1) Green

KI-20017G

Green

20 µL

5x

SE 6 (D6Z1) Blue

KI-20006B

Blue

20 µL

5x

SE 17 (D17Z1) Red

KI-20017R

Red

20 µL

5x

SE 6 (D6Z1) Green

KI-20006G

Green

20 µL

5x

SE 18 (D18Z1) Blue

KI-20018B

Blue

20 µL

5x

SE 6 (D6Z1) Red

KI-20006R

Red

20 µL

5x

SE 18 (D18Z1) Green

KI-20018G

Green

20 µL

5x

SE 7 (D7Z1) Blue

KI-20007B

Blue

20 µL

5x

SE 18 (D18Z1) Red

KI-20018R

Red

20 µL

5x

SE 7 (D7Z1) Green

KI-20007G

Green

20 µL

5x

SE 20 (D20Z1) Blue

KI-20020B

Blue

20 µL

5x

SE 7 (D7Z1) Red

KI-20007R

Red

20 µL

5x

SE 20 (D20Z1) Green

KI-20020G

Green

20 µL

5x

SE 8 (D8Z1) Blue

KI-20008B

Blue

20 µL

5x

SE 20 (D20Z1) Red

KI-20020R

Red

20 µL

5x

SE 8 (D8Z1) Green

KI-20008G

Green

20 µL

5x

SE X (DXZ1) Blue

KI-20023B

Blue

20 µL

5x

SE 8 (D8Z1) Red

KI-20008R

Red

20 µL

5x

SE X (DXZ1) Green

KI-20023G

Green

20 µL

5x

SE 9 (classical) Blue

KI-20009B

Blue

20 µL

5x

SE X (DXZ1) Red

KI-20023R

Red

20 µL

5x

SE 9 (classical) Green

KI-20009G

Green

20 µL

5x

SE Y (DYZ3) Blue

KI-20024B

Blue

20 µL

5x

SE 9 (classical) Red

KI-20009R

Red

20 µL

5x

SE Y (DYZ3) Green

KI-20024G

Green

20 µL

5x

SE 10 (D10Z1) Blue

KI-20010B

Blue

20 µL

5x

SE Y (DYZ3) Red

KI-20024R

Red

20 µL

5x

SE 10 (D10Z1) Green

KI-20010G

Green

20 µL

5x

SE Y class. q arm Blue

KI-20025B

Blue

20 µL

5x

SE 10 (D10Z1) Red

KI-20010R

Red

20 µL

5x

SE Y class. q arm Green

KI-20025G

Green

20 µL

5x

SE Y class. q arm Red

KI-20025R

Red

20 µL

5x

SE 11 (D11Z1) Blue

KI-20011B

Blue

20 µL

5x

SE 11 (D11Z1) Green

KI-20011G

Green

20 µL

5x

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

299

)

W

H

O

L

E

C

H

R

O

M

O

S

O

M

E

F

I

S

H

Product Name

Product code

Color

Content

Conc

Whole Chromosome 1 Red

KI-30001R

Red

10 µL

5x

Whole Chromosome 4 Red

KI-30004R

Red

10 µL

5x

Whole Chromosome 7 Green

KI-30007G

Green

10 µL

5x

Whole Chromosome 8 Green

KI-30008G

Green

10 µL

5x

Whole Chromosome 18 Green

KI-30018G

Green

10 µL

5x

Whole Chromosome 21 Green

KI-30021G

Green

10 µL

5x

Content

Conc

1 mL

10x

D

N

A

P

R

O

B

E

S

(

A

S

R

Product code

Human Satellite DNA

40V000V000

Human Satellite DNA, Flu labeled

40V000V495

Green

1 mL

10x

PapV-06, Flu labeled

40V006V495

Green

1 mL

10x

PapV-11, Flu labeled

40V011V495

Green

1 mL

10x

PapV-16, Flu labeled

40V016V495

Green

1 mL

10x

PapV-18, Flu labeled

40V018V495

Green

1 mL

10x

PapV-31, Flu labeled

40V031V495

Green

1 mL

10x

PapV-33, Flu labeled

40V033V495

Green

1 mL

10x

N

A

P

R

O

B

E

S

(

A

S

Color

R

Product code

Content

EBER Probe

ISH5687-A

7 mL

CMV Probe

ISH5719-A

7 mL

Kappa Probe

ISH5748-A

7 mL

Lambda Probe

ISH5770-A

7 mL

RNA Positive Controle Probe

ISH5894-A

7 mL

RNA Negative Controle Probe

ISH5950-A

7 mL

C

D

R

N

A

P

R

O

B

E

S

O

B

E

S

(

A

S

R

)

Product Name

A

R

)

Product Name

R

P

(

R

Product Name

Product code

Content

CMV Probe

RS775014 mL

EBV Probe

RS7751

14 mL

Albumin Probe

RS7752

14 mL

TTF-1 Probe

RS775314 mL

Napsin A Probe

RS7754

14 mL

PPIB (Positive Control)

RS7755

14 mL

dapB (Negative Control)

RS7756

14 mL

U

O

)

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

300

)

M

A

N

U

A

L

A

N

C

I

L

L

A

R

I

E

S

(

M

O

L

E

C

U

L

A

R

CONCENTRATION)PRODUCT NAMEPRODUCT CODECONTENT

Tissue Digestion Kit II

KBI-60004

Kit

IVD

Tissue Digestion Kit II

KI-60004

Kit

RUO

FISH Reagent Kit

KBI-60005

Kit

IVD

FISH Reagent Kit

KI-60005

Kit

RUO

FISH Digestion Kit

KBI-60006

Kit

IVD

FISH Digestion Kit

KI-60006

Kit

RUO

Tissue Digestion Kit I

KBI-60007

Kit

IVD

Tissue Digestion Kit I

KI-60007Kit

RUO

KREAvital Prenatal Medium (Basal)

KBI-90010

90 mL

RTU

IVD

KREAvital Prenatal Medium (Supplement)

KBI-90011

10 mL

RTU

IVD

KREAvital Prenatal Medium (Complete)

KBI-90012

100 mL

RTU

IVD

KREAvital Prenatal Medium PLUS (Complete)

KBI-90013

100 mL

RTU

IVD

KREAvital Lymphocyte Karyotyping Medium (without PHA)

KBI-90020

100 mL

RTU

IVD

KREAvital Lymphocyte Karyotyping Medium (including PHA)

KBI-90021

5 mL

RTU

IVD

KREAvital Bone Marrow Karyotyping Medium

KBI-90030

100 mL

RTU

IVD

KREAvital Myeloid Cell Medium

KBI-90031

100 mL

RTU

IVD

Colchicine Solution (10µg/ml, in PBS)

KBI-90050

25 mL

RTU

IVD

Colcemid Solution (10µg/ml, in PBS)

KBI-90051

10 mL

RTU

IVD

Potassium Chloride (0.075M)

KBI-90052

100 mL

RTU

IVD

Sodium Citrate Solution (0.8%)

KBI-90054

500 mL

RTU

IVD

Phytohaemagglutinin liquid

KBI-90056

5 mL

RTU

IVD

KREAvital Prenatal Medium (Complete)

KBI-92012

500 mL

RTU

IVD

KREAvital Lymphocyte Karyotyping Medium (without PHA)

KBI-92020

500 mL

RTU

IVD

Trypsin EDTA 10X (EDTA 0.2%, Trypsin 0.5%, in saline solution)

KBI-92055

100 mL

RTU

IVD

FISH Hybridization Buffer (FHB)

KBI-FHB

10 testRTU

GPR

FISH Hybridization Buffer (FHB)

KI-FHB

10 testRTU

GPR

Paraffin Tissue Buffer (PTB)

KBI-PTB

10 testRTU

GPR

Whole Chromosome Buffer (WCB)KBI-WCB

10 testRTU

GPR

Whole Chromosome Buffer (WCB)

KI-WCB

10 testRTU

GPR

20 x SSC

LK-061A

100 mLRTU

GPR

Fixogum Rubber Cement

LK-071A

125 grRTU

GPR

DAPI Counterstain (0.1 µg/ml)

LK-095A

1 mL

RTU

GPR

DAPI Counterstain (1 µg/ml)

LK-096A

1 mL

RTU

GPR

Counterstain Diluent

LK-097A

1 mL

RTU

GPR

Pretreatment Solution B

LK-100C

1L

RTU

GPR

Pepsin Solution

LK-101A

2,5 mL

RTU

GPR

Wash Buffer I

LK-102A

100 mL

RTU

GPR

Wash Buffer II

LK-103A

100 mL

RTU

GPR

Pretreatment Solution A

LK-110C

1L

RTU

GPR

Wash Buffer V (10x)LK-141B

250 mL

10x

GPR

Wash Buffer V (10x)LK-141C

1L

10x

GPR

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

301

CLASSIFICATION

H

U

G

O

G

E

N

E

C

O

N

V

E

R

S

I

O

N

T A

B

L

E

CHROMOSOMEPOSITIONPREVIOUS KREATECHNAMENEW KREATECHHUGO NAME

CHROMOSOMEPOSITIONPREVIOUS KREATECHNAMENEW KREATECHHUGO NAME

1p36

CHD5

CHD5

8q24

C-MYC

MYC

1p34

MYCL

MYCL

9p24

JAK2

JAK2

1q21

S100A10

S100A109p21

MLLT3, AF9

MLLT3

1q21

CKS1B

CKS1B

9p21

p16

CDKN2A

1q32

MDM4

MDM4

9q34

ABL

ABL1

2p24

MYCN, NMYC

MYCN

9q34

ASS

ASS1

2p23

ALK

ALK

9q34

NUP214, CAN

NUP214

2p21

EML4

EML4

10q11

RET

RET

2q11

LAF

AFF3

10q23

PTEN

PTEN

3p25

PPARy

PPARG

10q26

FGFR2

FGFR2

3q26

hTERC

TERC

11p15

NUP98

NUP98

3q26

EVI

MECOM

11q13

BCL1

CCND1

3q27

BCL6

BCL6

11q13

MYEOV

MYEOV

4p16

FGFR3

FGFR3

11q22

ATM

ATM

4p16

WHSC1, MMSET

WHSC1

11q23

MLL

KMT2A

4q12

FIP1L1FIP1L1

11q23

PLZF

ZBTB16

4q12

CHIC2

CHIC2

12p13

TEL

ETV6

4q12

PDGFRAPDGFRA

12q13

CDK4

CDK4

4q21-22

AFF1, MLLT2

AFF1

12q13

CHOP

DDIT3

5p15

hTERT

TERT

12q13

GLI

GLI1

5p15

CTNND

CTNND2

12q15

MDM2

MDM2

5q31

CDC25C

CDC25C

13q14

DLEU

DLEU1

5q31

EGR1

EGR1

13q14

FKHR

FOXO1

5q33

PDGFRBPDGFRB

14q32

IGH@

IGH

5q33

CSF1R

CSF1R

15q11

SNRPN

SNRPN

5q33

RPS14

RPS14

15q11

UBE3A

UBE3A

5q35

NSD1

NSD1

15q22

SMAD6

SMAD6

5q35

FGFR4

FGFR4

15q24

PML

PML

6p25

DUSP22

DUSP22

15q26

IGF1R

IGF1R

6p25

IRF4

IRF4

16p11

FUS

FUS

6p24

RREB1

RREB1

16q22

CBFB

CBFB

6p23

MYB

MYB

16q23

MAF

MAF

6p22

DEK

DEK

17p13

AURKB

AURKB

6p21

CCND3

CCND3

17p13

LIS

PAFAH1B1

6q21

SEC63

SEC63

17p13

p53

TP53

6q22

ROS1

ROS1

17p11

RAI1

RAI1

6q27

MLLT4, AF6

MLLT4

17q11

NF1

NF1

7p11

EGFR, Her1

EGFR

17q12

ERBB2, HER2

ERBB2

7q11

ELN

ELN

17q21

COL1A1COL1A1

7q11

LIMK1

LIMK1

17q21

RARA

RARA

7q22

CUTL1

CUX1

17q21

TOP2A

TOP2A

7q31

C-MET

MET

17q22

MPO

MPO

7q31

MDFIC

MDFIC

18q11

SYT

SS18

8p23

GATA4

GATA4

18q21

MALT

MALT1

8p21

PNOC

PNOC

18q21

BCL2

BCL2

8p11

FGFR1

FGFR1

19p13

MLLT1, ENL

MLLT1

8q21

ETO

RUNX1T

19p13

ZNF443

ZNF443* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
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H

U

G

O

G

E

N

E

C

O

N

V

E

R

S

I

O

N

T

A

B

L

E

CHROMOSOMEPOSITIONPREVIOUS KREATECHNAMENEW KREATECHHUGO NAME

CHROMOSOMEPOSITIONPREVIOUS KREATECHNAMENEW KREATECHHUGO NAME

19q13

CD37

CD37

22q11

CLH22

CLTCL1

19q13

ERCC1

ERCC1

22q11

DGCR2

DGCR2

20p11

NINL

NINL

22q11

TBX1

TBX1

20q11

MAPRE1

MAPRE1

22q11

TUPLE

HIRA

20q12

MAFB

MAFB

22q12

EWSR1

EWSR1

20q12

PTPRT

PTPRT

22q13

ARSA

ARSA

20q13

AURKA

AURKA

22q13

PDGFB

PDGFB

20q13

NFATC2NFATC222q13

SHANK3SHANK3

20q13

ZNF217

ZNF217

Xp22

KAL

KAL1

21q22

AML

RUNX1

Xp22

SHOX

SHOX

21q22

DSCR1

RCAN1

Xp22

STS

STS

21q22

ERG

ERG

Xp11

TFE3

TFE3

21q22

TMPRSS2TMPRSS2

Xq12

AR

AR

22q11

BCR

BCR

Xq13

XIST

XIST

* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
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INDEXCONTENTS..................................................................................................... 2

BOND CISH PROBES...........................................................................32

HOW TO USE THIS CATALOG........................................................................ 3

BOND KAPPA PROBE.................................................................................. 32

ADDITIONAL INFORMATION......................................................................... 3

BOND LAMBDA PROBE............................................................................... 32

KEY................................................................................................................. 3

BOND EBER PROBE..................................................................................... 33

AUTOMATED........................................................................................4

BOND CMV PROBE...................................................................................... 33

BOND ECOSYSTEM....................................................................................... 6

BOND HPV (SUBTYPES 6, 11) PROBE......................................................... 34

BOND-III......................................................................................................... 7

BOND HPV (SUBTYPES 16, 18, 31, 33, 51) PROBE..................................... 34

BOND-MAX..................................................................................................... 7

BOND DNA POSITIVE CONTROL................................................................. 35

BOND RX........................................................................................................ 9

BOND DNA NEGATIVE CONTROL............................................................... 35

BOND RXM..................................................................................................... 9

BOND RNA POSITIVE CONTROL PROBE.................................................... 35

CEREBRO..................................................................................................... 11

BOND RNA NEGATIVE CONTROL PROBE................................................... 35

THERMOBRITE............................................................................................ 13

BOND ANCILLARIES...........................................................................36

THERMOBRITE ELITE.................................................................................. 14

BOND DEWAX SOLUTION............................................................................ 36

COMPANION DIAGNOSTICS...............................................................15

BOND WASH SOLUTION 10X CONCENTRATE............................................ 36

BOND ORACLE HER2 IHC SYSTEM............................................................. 15

BOND EPITOPE RETRIEVAL SOLUTION 1................................................... 37

LEICA HER2 FISH SYSTEM......................................................................... 17

BOND EPITOPE RETRIEVAL SOLUTION 2................................................... 37

ADVANCED STAINING – BOND DETECTION.........................................21

BOND UNIVERSAL COVERTILE................................................................... 38

BOND POLYMER REFINE DETECTION........................................................ 21

BOND PRIMARY ANTIBODY DILUENT......................................................... 38

BOND POLYMER REFINE RED DETECTION ................................................ 21

BOND ENZYME PRETREATMENT KIT......................................................... 39

CHROMOPLEX 1 DUAL DETECTION........................................................... 22

BOND DAB ENHANCER............................................................................... 39

BOND FISH KIT............................................................................................ 22

BOND ANTI-FLUORESCEIN ANTIBODY....................................................... 40

BOND INTENSE R DETECTION ................................................................... 23

BOND HYBRIDIZATION SOLUTION............................................................. 40

BOND RESEARCH DETECTION ................................................................... 23

BOND ANTI-BIOTIN ANTIBODY................................................................... 40

BOND RNASCOPE DETECTION REAGENTS - BROWN................................ 24

BOND STRINGENCY WASH......................................................................... 41

BOND READY-TO-USE ANTIBODIES....................................................25

BOND RNASCOPE PROTEASE.................................................................... 41

XL FISH PROBES FOR BOND...............................................................27

BOND CONSUMABLES........................................................................42

2P23 ALK (2P23) BREAK57........................................................................ 27

BOND ASPIRATING PROBE CLEANING SYSTEM....................................... 42

6Q22 ROS1 (6Q22) BREAK57...................................................................... 27

BOND MIXING STATIONS............................................................................ 42

7Q31 MET (7Q31) / SE7 (D7Z1)57.............................................................. 28

BOND OPEN CONTAINERS 7 ML................................................................. 42

8P11 FGFR1 (8P11) / SE8 (D8Z1)57........................................................... 28

BOND OPEN CONTAINERS 30 ML.............................................................. 42

10Q11 RET (10Q11) BREAK57.................................................................... 29

BOND TITRATION KIT.................................................................................. 43

8Q24 MYC (8Q24) BREAK57....................................................................... 29

BOND TITRATION CONTAINER INSERTS.................................................... 43

14Q32 IGH (14Q32) BREAK57.................................................................... 30

BOND SLIDE LABEL AND PRINT RIBBON KIT............................................. 43

18Q21 BCL2 (18Q21) BREAK57.................................................................. 30

BOND REAGENT TRAY................................................................................. 43

3Q27 BCL6 (3Q27) BREAK57...................................................................... 31

BOND SLIDE TRAY....................................................................................... 44

17P13 TP53 (17P13) / SE 1757.................................................................. 31

BOND SYRINGE (FOR 9-PORT PUMP)......................................................... 44* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
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INDEX
BOND PLUS SLIDES..................................................................................... 45

CALCITONIN................................................................................................ 62

BOND COVERTILE CLEANING RACK.......................................................... 45

CALPAIN ANTIBODIES................................................................................ 62

MANUAL DETECTION.........................................................................46

CALPONIN (BASIC)..................................................................................... 63

NOVOLINK MAX POLYMER DETECTION SYSTEM ..................................... 47

CALRETININ................................................................................................ 63

NOVOLINK POLYMER DETECTION SYSTEM.............................................. 47

CARBONIC ANHYDRASE IX......................................................................... 64

NOVOLINK MIN POLYMER DETECTION SYSTEM....................................... 47

CARCINOEMBRYONIC ANTIGEN (CD66E).................................................. 64

PEROXIDASE BLOCK .................................................................................. 47

CAVEOLIN-1................................................................................................. 65

PROTEIN BLOCK ......................................................................................... 47

CD1A............................................................................................................ 65

NOVOLINK MAX POLYMER ........................................................................ 48

CD2 (LFA-2).................................................................................................. 66

NOVOLINK POLYMER ................................................................................. 48

CD3............................................................................................................... 66

NOVOLINK MAX DAB (POLYMER) .............................................................. 48

CD4............................................................................................................... 67

NOVOLINK DAB (POLYMER) ....................................................................... 48

CD5............................................................................................................... 67

HEMATOXYLIN ........................................................................................... 48

CD7............................................................................................................... 68

PEROXIDASE DETECTION SYSTEMS (READY-TO-USE) ............................. 48

CD8............................................................................................................... 68

STREPTAVIDIN-HRP ................................................................................... 49

CD10............................................................................................................ 69

AVIDIN/BIOTIN BLOCKING SYSTEM .......................................................... 49

CD11C.......................................................................................................... 69

ANTIBODY DILUENT.................................................................................... 50

CD13............................................................................................................ 70

ENZYME PROTEINASE K (IHC)................................................................... 50

CD15............................................................................................................ 70

EPITOPE RETRIEVAL SOLUTIONS PH6 ..................................................... 50

CD16............................................................................................................ 71

EPITOPE RETRIEVAL SOLUTIONS PH9 ..................................................... 51

CD19............................................................................................................ 71

MANUAL ANCILLARIES - MOLECULAR................................................52

CD20............................................................................................................ 72

ANTIBODIES......................................................................................53

CD21............................................................................................................ 72

AKT (PHOSPHORYLATED).......................................................................... 55

CD22............................................................................................................ 73

ALK............................................................................................................... 55

CD23............................................................................................................ 73

ALPHA FETOPROTEIN................................................................................ 56

CD25............................................................................................................ 74

ALPHA-METHYLACYL-COA RACEMASE (AMACR, P504S)........................ 56

CD30............................................................................................................ 74

ALPHA-SYNUCLEIN..................................................................................... 57

CD31 (PECAM-1)......................................................................................... 75

ANDROGEN RECEPTOR............................................................................... 57

CD33............................................................................................................ 75

AURORA KINASE 2...................................................................................... 58

CD34 (ENDOTHELIAL CELL MARKER)........................................................ 76

B CELL SPECIFIC OCTAMER BINDING PROTEIN-1 (BOB-1)....................... 58

CD38............................................................................................................ 76

BCL-2 ONCOPROTEIN................................................................................. 59

CD43............................................................................................................ 77

BCL-6 ONCOPROTEIN................................................................................. 59

CD45............................................................................................................ 77

BETA-CATENIN............................................................................................ 60

CD45RO........................................................................................................ 78

BETA-DYSTROGLYCAN................................................................................ 60

CD56 (NCAM).............................................................................................. 78

CA125 (OVARIAN CANCER ANTIGEN)........................................................ 61

CD57............................................................................................................ 79

CA19-9 (SIALYL LEWIS A)............................................................................ 61

CD61 (GPIIIA).............................................................................................. 79* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
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INDEX
CD68............................................................................................................ 80

EPIDERMAL GROWTH FACTOR RECEPTOR............................................... 98

CD71............................................................................................................ 80

EPITHELIAL MEMBRANE ANTIGEN............................................................ 98

CD79A.......................................................................................................... 81

ESTROGEN RECEPTOR................................................................................ 99

CD79B.......................................................................................................... 81

EZH2 (ENHANCER OF ZESTE HOMOLOG 2 (DROSOPHILA))..................... 99

CD99............................................................................................................ 82

FACTOR XIIIA (BLOOD COAGULATION FACTOR XIIIA)............................. 100

CD103.......................................................................................................... 82

FASCIN....................................................................................................... 100

CD117.......................................................................................................... 83

FOLATE RECEPTOR ALPHA...................................................................... 101

CD123.......................................................................................................... 83

GALECTIN-3............................................................................................... 101

CD138 (SYNDECAN 1)................................................................................. 84

GASTRIN.................................................................................................... 102

CD141 (THROMBOMODULIN)..................................................................... 84

GEMININ.................................................................................................... 102

CD146 (MCAM)............................................................................................ 85

GLIAL FIBRILLARY ACIDIC PROTEIN........................................................ 103

CD163.......................................................................................................... 85

GLUTATHIONE S-TRANSFERASE (GST) ANTIBODY................................. 103

CDX2............................................................................................................ 86

GRANZYME B............................................................................................. 104

C-ERBB-2 ONCOPROTEIN (HER-2) ANTIBODIES........................................ 86

GROSS CYSTIC DISEASE FLUID PROTEIN-15........................................... 104

CHROMOGRANIN A..................................................................................... 87

HELICOBACTER PYLORI............................................................................ 105

CYCLIN D1................................................................................................... 87

HUMAN CHORIONIC GONADOTROPHIN (BETA)..................................... 105

CYTOKERATIN 5.......................................................................................... 88

HUMAN FOLLICLE STIMULATING HORMONE (BETA 2) (HFSH)............. 106

CYTOKERATIN 7.......................................................................................... 88

HUMAN GROWTH HORMONE (HGH)........................................................ 106

CYTOKERATIN 8.......................................................................................... 89

HUMAN HERPESVIRUS 8 (HHV8)............................................................. 107

CYTOKERATIN 14........................................................................................ 89

IMMUNOGLOBULIN A................................................................................ 107

CYTOKERATIN 17........................................................................................ 90

IMMUNOGLOBULIN D................................................................................ 108

CYTOKERATIN 18........................................................................................ 90

IMMUNOGLOBULIN G............................................................................... 108

CYTOKERATIN 19........................................................................................ 91

IMMUNOGLOBULIN M............................................................................... 109

CYTOKERATIN 20........................................................................................ 91

INHIBIN ALPHA......................................................................................... 109

CYTOKERATIN (5/6/18)............................................................................... 92

INSULIN..................................................................................................... 110

CYTOKERATIN (8/18).................................................................................. 92

INTERLEUKIN 6.......................................................................................... 110

CYTOKERATIN, MULTI (1/5/10/14) (HIGH MOLECULAR WEIGHT)............ 93

KAPPA LIGHT CHAIN................................................................................ 111

CYTOKERATIN, MULTI (4/5/6/8/10/13/18)................................................ 93

KI67 ANTIGEN........................................................................................... 111

CYTOKERATIN, MULTI (5/6/8/18)............................................................... 94

LAMBDA LIGHT CHAIN............................................................................. 112

CYTOKERATIN, MULTI (AE1/AE3)............................................................... 94

LANGERIN.................................................................................................. 112

DESMIN........................................................................................................ 95

LYSOZYME (MURAMIDASE)...................................................................... 113

DOG-1........................................................................................................... 95

MAMMAGLOBIN........................................................................................ 113

DYSFERLIN ANTIBODIES............................................................................ 96

MAST CELL TRYPTASE............................................................................. 114

DYSTROPHIN ANTIBODIES......................................................................... 96

MELAN A.................................................................................................... 114

E-CADHERIN................................................................................................ 97

MELANOMA MARKER (HMB45)............................................................... 115

EMERIN........................................................................................................ 97

MEROSIN LAMININ ALPHA 2 CHAIN....................................................... 115* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
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INDEXMESOTHELIN............................................................................................. 116

PD-L1.......................................................................................................... 134

MICROPHTHALMIA TRANSCRIPTION FACTOR (MITF)........................... 116

PERFORIN.................................................................................................. 134

MISMATCH REPAIR PROTEIN (MLH1)...................................................... 117

PLACENTAL ALKALINE PHOSPHATASE.................................................. 135

MISMATCH REPAIR PROTEIN (MSH2)...................................................... 117

POLO-LIKE KINASE 1 (PLK-1).................................................................... 135

MISMATCH REPAIR PROTEIN (MSH6)...................................................... 118

PROGESTERONE RECEPTOR.................................................................... 136

MISMATCH REPAIR PROTEIN (PMS2)...................................................... 118

PROGESTERONE RECEPTOR (A/B FORMS).............................................. 136

MUC-1 GLYCOPROTEIN............................................................................. 119

PROSTATE SPECIFIC ANTIGEN................................................................ 137

MUC-2 GLYCOPROTEIN............................................................................. 119

PROSTATE SPECIFIC MEMBRANE ANTIGEN........................................... 137

MUC-5AC GLYCOPROTEIN........................................................................ 120

PROSTATIC ACID PHOSPHATASE............................................................ 138

MUC-6 GLYCOPROTEIN............................................................................. 120

PROTEIN GENE PRODUCT 9.5.................................................................. 138

MULTIPLE MYELOMA ONCOGENE 1 (MUM-1)......................................... 121

RETINOBLASTOMA GENE PROTEIN......................................................... 139

MUSCLE SPECIFIC ACTIN......................................................................... 121

S-100.......................................................................................................... 139

MYELOPEROXIDASE.................................................................................. 122

SARCOGLYCAN ANTIBODIES.................................................................... 140

MYOD1 (RHABDOMYOSARCOMA MARKER)............................................ 122

SEROTONIN............................................................................................... 140

MYOGENIN (MYF-4)................................................................................... 123

SMA (ALPHA SMOOTH MUSCLE ACTIN)................................................. 141

MYOGLOBIN............................................................................................... 123

SPECTRIN.................................................................................................. 141

MYOSIN HEAVY CHAIN ANTIBODIES....................................................... 124

SURFACTANT PROTEIN A......................................................................... 142

MYOTILIN................................................................................................... 124

SYNAPTOPHYSIN...................................................................................... 142

NAPSIN A................................................................................................... 125

TARTRATE-RESISTANT ACID PHOSPHATASE (TRAP)............................. 143

N-CADHERIN.............................................................................................. 125

TERMINAL DEOXYNUCLEOTIDYL TRANSFERASE................................... 143

NEGATIVE CONTROL (MOUSE)................................................................. 126

THYROGLOBULIN...................................................................................... 144

NEGATIVE CONTROL (RABBIT)................................................................. 126

THYROID PEROXIDASE............................................................................. 144

NEUROFILAMENT 200KD.......................................................................... 127

THYROID STIMULATING HORMONE........................................................ 145

NEURON SPECIFIC ENOLASE................................................................... 127

THYROID TRANSCRIPTION FACTOR-1..................................................... 145

NITRIC OXIDE SYNTHASE 1...................................................................... 128

TOPOISOMERASE I.................................................................................... 146

OCT-02........................................................................................................ 128

TOPOISOMERASE II ALPHA...................................................................... 146

OCT-3/4...................................................................................................... 129

TYROSINASE............................................................................................. 147

P16............................................................................................................. 129

TYROSINE HYDROXYLASE........................................................................ 147

P21 (WAF1 PROTEIN)................................................................................ 130

UTROPHIN................................................................................................. 148

P53 PROTEIN............................................................................................. 130

VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-3................... 148

P53 PROTEIN (CM5).................................................................................. 131

VILLIN........................................................................................................ 149

P57 PROTEIN (KIP2).................................................................................. 131

VIMENTIN.................................................................................................. 149

P63 PROTEIN............................................................................................. 132

VON WILLEBRAND FACTOR (FACTOR VIII-RELATED ANTIGEN).............. 150

P120 CATENIN........................................................................................... 132

WILMS’ TUMOR.......................................................................................... 150

PARATHYROID HORMONE (PTH).............................................................. 133

ZAP-70....................................................................................................... 151

PAX-5.......................................................................................................... 133

CELL MARQUE.................................................................................152* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

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INDEX
IVD PROBES.....................................................................................153

CDK4 / SE 1257......................................................................................... 172

11Q23 / DLEU157...................................................................................... 155

CDKN2A / 9Q2157..................................................................................... 173

15Q22 / 6Q2157........................................................................................ 155

CDKN2A / 9Q21 (TISSUE)57..................................................................... 173

15Q22 / 9Q3457........................................................................................ 156

COL1A1 / PDGFB57................................................................................... 174

19Q13 / TP5357........................................................................................ 156

CRLF2 / IGH57........................................................................................... 174

1Q21 / 8P2157.......................................................................................... 157

CTNND257................................................................................................. 175

1Q21 / SRD57............................................................................................ 157

DDIT3 BREAK57......................................................................................... 175

20Q-57........................................................................................................ 158

DEK / NUP21457....................................................................................... 176

5Q DUAL-COLOR57.................................................................................... 158

DIC(9;20)57................................................................................................ 176

5Q- TRIPLE-COLOR57................................................................................ 159

DIGEORGE II / SE 1057.............................................................................. 177

6Q21 / MYC57........................................................................................... 159

DLEU1 / 13QTER57.................................................................................... 177

6Q21 / SE 657............................................................................................ 160

DLEU1 / TP5357........................................................................................ 178

7Q-57.......................................................................................................... 160

EGFR / SE 757............................................................................................ 178

7Q- TRIPLE-COLOR57................................................................................ 161

ELN / 7Q2257............................................................................................ 179

ACRO-P-ARMS57....................................................................................... 161

ERBB2 / SE 1757....................................................................................... 179

ALK / EML457............................................................................................ 162

ERCC1 / ZNF44357................................................................................... 180

ALK BREAK57............................................................................................ 162

ETV6 / RUNX157....................................................................................... 180

AR / SE X57................................................................................................ 163

ETV6 BREAK57.......................................................................................... 181

ATM / GLI157............................................................................................. 163

EWSR1 / NFATC57..................................................................................... 181

ATM / SE 1157........................................................................................... 164

EWSR1 BREAK57....................................................................................... 182

AURKA57................................................................................................... 164

FGFR1 / SE 857.......................................................................................... 182

AURKB57.................................................................................................... 165

FGFR1 BREAK57........................................................................................ 183

BCL2 / IGH57............................................................................................. 165

FGFR2 / SE 1057........................................................................................ 183

BCL2 / IGH (TISSUE)57............................................................................. 166

FGFR3 / IGH57........................................................................................... 184

BCL2 BREAK57.......................................................................................... 166

FGFR4 / 5Q11.257..................................................................................... 184

BCL2 BREAK (TISSUE)57.......................................................................... 167

FIP1L1 / CHIC2 /PDGFRA DUAL-COLOR57.............................................. 185

BCL6 BREAK57.......................................................................................... 167

FIP1L1 / CHIC2 /PDGFRA TRIPLE-COLOR57............................................ 185

BCL6 BREAK (TISSUE)57.......................................................................... 168

FOXO1 BREAK57....................................................................................... 186

BCR / ABL157............................................................................................ 168

FUS BREAK57............................................................................................ 186

BCR / ABL1 DC57...................................................................................... 169

GATA4 / SE 857......................................................................................... 187

BCR / ABL1 DC ES57................................................................................. 169

GLI1 / SE 1257........................................................................................... 187

BCR / ABL1 TC57....................................................................................... 170

HIRA / SHANK357..................................................................................... 188

CBFB BREAK57.......................................................................................... 170

IGF1R / 15Q1157....................................................................................... 188

CCND1 / IGH FUSION57............................................................................ 171

IGH BREAK57............................................................................................. 189

CCND1 /SE 1157....................................................................................... 171

IGH BREAK (TISSUE)57............................................................................. 189

CCND1 BREAK57....................................................................................... 172

IRF4 / DUSP22 BREAK57........................................................................... 190* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

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INDEX
JAK2 BREAK57.......................................................................................... 190

RB1 / RCAN1, SE X/SE Y/ SE 1857............................................................ 208

KMT2A / AFF157....................................................................................... 191

RCAN157................................................................................................... 209

KMT2A / MLLT157..................................................................................... 191

RCAN1 / SE X / SE Y57.............................................................................. 209

KMT2A / MLLT357..................................................................................... 192

RET BREAK57............................................................................................ 210

KMT2A / MLLT457..................................................................................... 192

ROS1 BREAK57.......................................................................................... 210

KMT2A / SE 1157...................................................................................... 193

RUNX1 / RUNX1T157................................................................................ 211

KMT2A BREAK57....................................................................................... 193

SE 18 (D18Z1)57........................................................................................ 211

MAF/ IGH57............................................................................................... 194

SE 7 / SE 857............................................................................................. 212

MAFB /IGH57............................................................................................. 194

SE X / SE Y57............................................................................................. 212

MALT1 BREAK57....................................................................................... 195

SE X / SE Y / SE 1857................................................................................. 213

MALT1 BREAK (TISSUE)57........................................................................ 195

SHOX / SE X57........................................................................................... 213

MDM2 / SE 1257........................................................................................ 196

SNRPN / PML57........................................................................................ 214

MDM4 / SE 157.......................................................................................... 196

SRD / SE 157.............................................................................................. 214

MECOM BREAK57..................................................................................... 197

SS18 BREAK57.......................................................................................... 215

MECOM BREAK TRIPLE-COLOR57............................................................ 197

STS / KAL1 / SE X57.................................................................................. 215

MECOM/RUNX157.................................................................................... 198

TBX1 / SHANK357..................................................................................... 216

MET / SE 757............................................................................................. 198

TERC / 3Q1157.......................................................................................... 216

MM-BCR / ABL157..................................................................................... 199

TERC / MYC / SE 757................................................................................. 217

MYC (8Q24) BREAK57............................................................................... 199

TERT / 5Q3157........................................................................................... 217

MYC (8Q24) BREAK (TISSUE)57............................................................... 200

TERT / 5Q31 (TISSUE)57........................................................................... 218

MYC / SE 857............................................................................................. 200

TFE3 BREAK57.......................................................................................... 218

MYC / IGH T(8;14) FUSION57.................................................................... 201

TMPRSS2-ERG57....................................................................................... 219

MYCN / AFF357......................................................................................... 201

TOP2A / ERBB2 / SE 1757......................................................................... 219

MYEOV / IGH57......................................................................................... 202

TOP2A / SE 1757....................................................................................... 220“N25” / SHANK357.................................................................................... 202

TP53 / ATM57............................................................................................ 220

NF1 / MPO57............................................................................................. 203

TP53 / MPO57........................................................................................... 221

NSD1 / TERT57.......................................................................................... 203

TP53 / SE 1757.......................................................................................... 221

NUP98 BREAK57....................................................................................... 204

TP53 / SE 17 (TISSUE)57.......................................................................... 222

PAFAH1B1 / 17P1157............................................................................... 204

UBE3A / PML57......................................................................................... 222

PDGFRB BREAK57..................................................................................... 205

WHSC1 / SE 457........................................................................................ 223

PML / RARA57........................................................................................... 205

XIST / SE X57............................................................................................. 223

PPARG BREAK57....................................................................................... 206

ZNF217 / 20Q1157.................................................................................... 224

PTEN / SE 1057......................................................................................... 206

SATELLITE ENUMERATION FISH PROBES (IVD).................................225

RARA BREAK57......................................................................................... 207

WHOLE CHROMOSOME FISH PROBES (IVD)......................................226

RB157......................................................................................................... 207

SUB TELOMERIC FISH PROBES (IVD)................................................227

RB1 / RCAN157......................................................................................... 208

SUB TELOMERIC FISH PROBES (IVD)................................................228* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

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INDEXRUO PROBES.............................................................................................. 229

CDKN2A / 9Q2157..................................................................................... 248

11Q23 / DLEU157...................................................................................... 231

CDKN2A / 9Q21 (TISSUE)57..................................................................... 249

15Q22 / 6Q2157........................................................................................ 231

CTNND257................................................................................................. 249

15Q22 / 9Q3457........................................................................................ 232

DDIT3 BREAK57......................................................................................... 250

19Q13 / TP5357........................................................................................ 232

DEK / NUP21457....................................................................................... 250

1Q21 / 8P2157.......................................................................................... 233

DIC(9;20)57................................................................................................ 251

1Q21 / SRD57............................................................................................ 233

DIGEORGE II / SE 1057.............................................................................. 251

20Q-57........................................................................................................ 234

DLEU1 / 13QTER57.................................................................................... 252

5Q DUAL-COLOR57.................................................................................... 234

DLEU1 / TP5357........................................................................................ 252

5Q- TRIPLE-COLOR57................................................................................ 235

EGFR / SE 757............................................................................................ 253

6Q21 / MYC57........................................................................................... 235

ELN / 7Q2257............................................................................................ 253

6Q21 / SE 657............................................................................................ 236

ERBB2 / SE 1757....................................................................................... 254

7Q-57.......................................................................................................... 236

ERCC1 / ZNF44357................................................................................... 254

7Q- TRIPLE-COLOR57................................................................................ 237

ETV6 / RUNX157....................................................................................... 255

ALK / EML457............................................................................................ 237

ETV6 BREAK57.......................................................................................... 255

ALK BREAK57............................................................................................ 238

EWSR1 / NFATC57..................................................................................... 256

AR / SE X57................................................................................................ 238

EWSR1 BREAK57....................................................................................... 256

ATM / GLI157............................................................................................. 239

FGFR1 BREAK57........................................................................................ 257

ATM / SE 1157........................................................................................... 239

FGFR2 / SE 1057........................................................................................ 257

AURKA57................................................................................................... 240

FGFR3 / IGH57........................................................................................... 258

AURKB57.................................................................................................... 240

FGFR4 / 5Q11.257..................................................................................... 258

BCL2 / IGH57............................................................................................. 241

FIP1L1 / CHIC2 /PDGFRA DUAL-COLOR57.............................................. 259

BCL2 / IGH (TISSUE)57............................................................................. 241

FIP1L1 / CHIC2 /PDGFRA TRIPLE-COLOR57............................................ 259

BCL2 BREAK57.......................................................................................... 242

FOXO1 BREAK57....................................................................................... 260

BCL2 BREAK (TISSUE)57.......................................................................... 242

FUS BREAK57............................................................................................ 260

BCL6 BREAK57.......................................................................................... 243

GATA4 / SE 857......................................................................................... 261

BCL6 BREAK (TISSUE)57.......................................................................... 243

GLI1 / SE 1257........................................................................................... 261

BCR / ABL157............................................................................................ 244

HIRA / SHANK357..................................................................................... 262

BCR / ABL1 DC57...................................................................................... 244

HUMAN CENTROMERE57......................................................................... 262

BCR / ABL1 DC ES57................................................................................. 245

IGF1R / 15Q1157....................................................................................... 263

BCR / ABL1 TC57....................................................................................... 245

IGH BREAK57............................................................................................. 263

CBFB BREAK57.......................................................................................... 246

IGH BREAK (TISSUE)57............................................................................. 264

CCND1 / IGH FUSION57............................................................................ 246

IRF4 / DUSP22 BREAK57........................................................................... 264

CCND1 /SE 1157....................................................................................... 247

JAK2 BREAK57.......................................................................................... 265

CCND1 BREAK57....................................................................................... 247

KMT2A / AFF157....................................................................................... 265

CDK4 / SE 1257......................................................................................... 248

KMT2A / MLLT157..................................................................................... 266* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

310

INDEXKMT2A / MLLT357..................................................................................... 266

SE 7 / SE 857............................................................................................. 284

KMT2A / MLLT457..................................................................................... 267

SE X / SE Y57............................................................................................. 285

KMT2A / SE 1157...................................................................................... 267

SE X / SE Y / SE 1857................................................................................. 285

KMT2A BREAK57....................................................................................... 268

SHOX / SE X57........................................................................................... 286

MAF/ IGH57............................................................................................... 268

SNRPN / PML57........................................................................................ 286

MAFB /IGH57............................................................................................. 269

SRD / SE 157.............................................................................................. 287

MALT1 BREAK57....................................................................................... 269

SS18 BREAK57.......................................................................................... 287

MALT1 BREAK (TISSUE)57........................................................................ 270

STS / KAL1 / SE X57.................................................................................. 288

MDM2 / SE 1257........................................................................................ 270

TBX1 / SHANK357..................................................................................... 288

MDM4 / SE 157.......................................................................................... 271

TERC / 3Q1157.......................................................................................... 289

MECOM BREAK57..................................................................................... 271

TERC / MYC / SE 757................................................................................. 289

MECOM BREAK TRIPLE-COLOR57............................................................ 272

TERT / 5Q3157........................................................................................... 290

MECOM / RUNX157................................................................................... 272

TERT / 5Q31 (TISSUE)57........................................................................... 290

MET / SE 757............................................................................................. 273

TFE3 BREAK57.......................................................................................... 291

MYC (8Q24) BREAK57............................................................................... 273

TMPRSS2-ERG57....................................................................................... 291

MYC (8Q24) BREAK (TISSUE)57............................................................... 274

TOP2A / ERBB2 / SE 1757......................................................................... 292

MYC / SE 857............................................................................................. 274

TOP2A / SE 1757....................................................................................... 292

MYC / IGH T(8;14) FUSION57.................................................................... 275

TP53 / ATM57............................................................................................ 293

MYCN / AFF357......................................................................................... 275

TP53 / MPO57........................................................................................... 293

MYEOV / IGH57......................................................................................... 276

TP53 / SE 1757.......................................................................................... 294“N25” / SHANK357.................................................................................... 276

TP53 / SE 17 (TISSUE)57.......................................................................... 294

NF1 / MPO57............................................................................................. 277

UBE3A / PML57......................................................................................... 295

NSD1 / TERT57.......................................................................................... 277

WHSC1 / SE 457........................................................................................ 295

NUP98 BREAK57....................................................................................... 278

XIST / SE X57............................................................................................. 296

PAFAH1B1 / 17P1157............................................................................... 278

ZNF217 / 20Q1157.................................................................................... 296

PDGFRB BREAK57..................................................................................... 279

MANUAL FISH PROBES (ASR)...........................................................297

PML / RARA57........................................................................................... 279

XL FISH PROBES (ASR)....................................................................298

PPARG BREAK57....................................................................................... 280

SATELLITE ENUMERATION FISH PROBES (ASR)................................299

PTEN / SE 1057......................................................................................... 280

WHOLE CHROMOSOME FISH PROBES (ASR).....................................300

RARA BREAK57......................................................................................... 281

DNA PROBES (ASR)..........................................................................300

RB1 / RCAN157......................................................................................... 281

RNA PROBES (ASR)..........................................................................300

RB1 / RCAN1, SE X/SE Y/ SE 1857............................................................ 282

ACD RNA PROBES (RUO)..................................................................300

RCAN1 / SE X / SE Y57.............................................................................. 282

MANUAL ANCILLARIES (MOLECULAR).............................................301

RET BREAK57............................................................................................ 283

HUGO GENE CONVERSION TABLE.....................................................302

ROS1 BREAK57.......................................................................................... 283

INDEX..............................................................................................304

RUNX1 / RUNX1T157................................................................................ 284* Products in this catalog are subject to regulatory approval. Please consult your Leica Biosystems Sales Representative for availability in your region.
IVD In Vitro Diagnostic Use RUO For Research Use Only. Not for use in diagnostic procedures ASR Analyte Specific Reagent GPR General Purpose Reagent

311

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190642 Rev B · 09/2020