bluuebunny/crossref_metadata_2025_split huggingface dataset:
Specific Changes of Chromatin Structure in Nuclei of Normal Epithelium Adjacent to Laryngeal Squamous Cell Carcinoma
Authors: Dreyer Thomas , Knoblauch Iris , Garner David , Doudkine Alexei , MacAulay Calum , Palcic Branko , Popella Christian 
Published: January 2015

The aim of this study was to confirm the existence of specific nuclear texture feature alterations of histologically normal epithelial borders nearby invasive laryngeal cancer (NC).Paraffin sections of NC and of chronic inflammations unrelated to cancer (CI) were analysed for nuclear texture and for integrated optical density (IOD‐index) and were compared to normal epithelium of patients without evidence of cancer (NE). Several discriminant functions based on nuclear texture features were trained to separate different subgroups.As the most important result, specific nuclear texture feature shifts were only found in NC with high‐density lymphocytic stroma infiltrate (NC+). Classification of nuclei of NE versus NC+ was correct in 70%. The same classifier was correct in only 58% when nuclei of NE were classified versus CI. We also found lower values of IOD‐Index within the NC+ group when compared to NE (p < 0:001).
DNA Ploidy and Chromosomal Imbalances in Invasive Ductal Breast Cancer. A Comparative Study of DNA Image Cytometry and Comparative Genomic Hybridization (CGH)
Authors: Friedrich Katrin , Scheithauer Jens , Dimmer Volker , Meyer Wolfdietrich , Theissig Franz , Haroske Gunter , Kunze Klaus Dietmar 
Published: January 2015

Chromosomal imbalances were analyzed in 62 breast cancers with different DNA ploidy by CGH. The results of DNA image cytometry and CGH are consistent with peridiploid and aneuploid cases. The peritetraploid tumors harbored a high number of chromosomal imbalances, as a hint for an unfavorable prognosis. The quantitative analysis of imbalances highlighted the role of different physical constituents of the chromosome, and of chromosomal losses in different DNA ploidy groups. The peritetraploid and aneuploid tumors differed from the peridiploid tumors in losses at 8p and 18q. The peritetraploid cancers exhibited more gains at 8q, the aneuploid tumors more losses at 17p than their peridiploid counterparts. The aneuploid cases differed from the peritetraploid tumors in a higher number of losses at 11q and 14q. Combinations of imbalances provide further insights into the genetic background of DNA ploidy. Hypotheses for the progression from peridiploid to nondiploid breast cancers are given.Figures on http://www.esacp.org/acp/2000/20-2_3/friedrich.htm.
Immunohistochemical Assessment of the Tumour‐Associated Epitopes CD44v6 and E48 in Tumour‐Free Lymph Nodes from Patients with Squamous Cell Carcinoma in the Head‐Neck Region
Authors: Fabricius Eva-Maria , Guschmann Michael , Langford Angelika , Hell Berthold , Bier Jürgen 
Published: January 2015

We examined immunohistochemically 370 tumour‐free lymph nodes from 41 patients with a head and neck squamous cell carcinoma (HNSCC) to clarify whether the tumour‐associated epitopes CD44v6 and E48 are suitable for adjuvant postoperative immunotherapy. All the positively immunostained cells found were single cells.CD44v6+ cells were found in 55% of the lymph nodes, with their numbers increasing in pN>0‐patients (62%). Only pN>0‐patients had abundant to massive CD44v6+ cells. A comparison with mononuclear cells in lymphatic tissue from control patients suggested a similarity with activated T‐cells. In the 41 cancer patients there were significantly fewer lymph nodes with E48+ cells (11%), but the number of E48+ cells increased in pN>1‐patients (29%) with predominantly abundant E48+ cells. We conclude from the comparison with the epithelial marker EMA that the E48+ single cells are epithelial in origin. Only a specific E48 peptide sequence appears suitable for adjuvant immunotherapy in patients with head‐neck tumours.
Intratumor Heterogeneity of K‐Ras and p53 Mutations among Human Colorectal Adenomas Containing Early Cancer
Authors: Giaretti Walter , Macciocu Barbara , Geido Elio , Hermsen Mario , Postma Cindy , Baak Jan , Williams Richard , Meijer Gerrit 
Published: January 2015

The molecular pathways and the timing of genetic events during human colorectal carcinogenesis are still not fully understood. We have addressed the intratumor heterogeneity of the mutational status of the k‐ras oncogene and of the p53 oncosuppressor gene during the adenoma–carcinoma sequence by investigating 26 human colorectal adenomas containing early cancer. An intratumor comparative analysis was obtained among the adenomatous and carcinomatous component pairs. Additionally, we have analyzed 17 adenomas having cancer in the near vicinity.
The adenomatous components of the adenomas containing early cancer and the adenomas having cancer in the near vicinity had comparable frequencies for k‐ras mutations (28 and 47%) but different for p53 mutations (52 and 7%, p‐value = 0.01). Interestingly, the adenomatous and carcinomatous components of the adenomas containing early cancer were rarely heterogeneous for the k‐ras mutational status (only in 13% of the cases) but were characterized by heterogeneity of the p53 status in 59% of the cases (p‐value < 0.01). In addition, the mutations of p53 for the adenomatous components of the adenomas containing early cancer were statistically significantly associated with severe dysplasia (p‐value = 0.01).
Intratumor homogeneity of k‐ras status during the human colorectal adenoma–carcinoma sequence suggests that the role of k‐ras is more related to tumor initiation than to tumor progression. On the contrary, intratumor heterogeneity of p53 mutations indicates that the type of the p53 mutations may also be relevant for selection and expansion of new subclones leading to tumor progression.Erratum to “Intratumor Heterogeneity of k-ras and p53 Mutations Among Human Colorectal Adenomas Containing Early Cancer”dx.doi.org/10.1155/2001/905923
Current Experiences with Internet Telepathology and Possible Evolution in the Next Generation of Internet Services
Authors: Della Mea V. , Beltrami C. A. 
Published: January 2015

The last five years experience has definitely demonstrated the possible applications of the Internet for telepathology. They may be listed as follows: (a) teleconsultation via multimedia e‐mail; (b) teleconsultation via web‐based tools; (c) distant education by means of World Wide Web; (d) virtual microscope management through Web and Java interfaces; (e) real‐time consultations through Internet‐based videoconferencing. Such applications have led to the recognition of some important limits of the Internet, when dealing with telemedicine: (i) no guarantees on the quality of service (QoS); (ii) inadequate security and privacy; (iii) for some countries, low bandwidth and thus low responsiveness for real‐time applications. Currently, there are several innovations in the world of the Internet. Different initiatives have been aimed at an amelioration of the Internet protocols, in order to have quality of service, multimedia support, security and other advanced services, together with greater bandwidth.The forthcoming Internet improvements, although induced by electronic commerce, video on demand, and other commercial needs, are of real interest also for telemedicine, because they solve the limits currently slowing down the use of Internet. When such new services will be available, telepathology applications may switch from research to daily practice in a fast way.
Technical Aspects of Telepathology with Emphasis on Future Development
Authors: Schwarzmann P. , Binder B. , Klose R. 
Published: January 2015

Pathology undergoes presently changes due to new developments in diagnostic opportunities and cost saving efforts in health care. Out of the wide field of telepathology the paper selects three prototype applications: telepathology in teleeducation, expert advice for preselected details of a slide and finally telepathology for remote diagnosis. The most challenging field for remote diagnosis is the application in the frozen section scenario. The paper starts with the mental experiment to map conventional procedures to counterparts in telepathology.Technical opportunities and economical restrictions of telepathology equipment are discussed with respect to the components: electronic camera, display devices, haptic sensors and displays, available telecommunication channels and telepathology software.As an example and for illustration of the state of the art for an advanced telemicroscopy system able to perform remote frozen section diagnosis, the HISTKOM equipment is presented in more details.The section concerning future developments regards the aspects of the acceptance by tentative users, legal aspects, costs and affordability of equipment, the market for equipment components and the adequate telecommunication services. Further is regarded the mutual influence of properties of existing systems and application experiences gained with them on the next generation of equipment and application software. Conclusions and references close the paper.
Heterogeneous Chromosomal Aberrations in Intraductal Breast Lesions Adjacent to Invasive Carcinoma
Authors: Aubele Michaela , Cummings Margaret , Walch Axel , Zitzelsberger Horst , Nährig Jörg , Höfler Heinz , Werner Martin 
Published: January 2015

There is evidence that breast cancer is a heterogeneous disease phenotypically as well as molecular biologically. So far, heterogeneity on the molecular biological level has not been investigated in potential precursor lesions, such as ductal hyperplasia (DH) and ductal carcinoma in situ (DCIS). In this study we applied comparative genomic hybridization (CGH) to formalin‐fixed, paraffin‐embedded breast tissue with DH and DCIS, adjacent to invasive ductal carcinoma (IDC), to screen these potential precursor lesions for whole genomic chromosomal imbalances. Laser‐microdissection was used to select pure cell populations from the sections. Isolated DNA was amplified by degenerate oligonucleotide primed PCR (DOP‐PCR) and further processed for CGH analysis.Investigating multiple samples (n=25) from four patients we found an average of 5.6 ± 0.9 (mean ± SEM) chromosomal imbalances already present in DH. In the twelve DCIS lesions an average of 10.8 (±0.9) aberrations was identified with 14.8 (±0.8) aberrations in the four adjacent IDC lesions. The increasing number of chromosomal changes in parallel with the histopathological sequence corroborate the hypothesis, that the carcinomas may have developed through a sequential progression from normal to proliferative epithelium and eventually into carcinoma. However, heterogeneous results were identified in the multiple samples per entity from the same patient, demonstrated mainly in the DCIS samples in the chromosomal regions 6p, 9p, 11q, 16p and 17q, in the DH samples by 3p, 16p and 17q. This heterogeneous findings were most pronounced within the DH and was less in the DCIS and IDC samples. The only aberration consistently found in all samples – even in all DH samples – was amplification of the 20q13 region.Our results demonstrate, that the applied combination of laser‐microdissection, DOP‐PCR and CGH, may serve to analyse breast carcinogenesis pathways in suitable histological material. However, so far, it is unclear how to handle heterogeneous results and these make identification of relevant changes more difficult. Setting a threshold and valuating only those chromosomal changes which are present in a majority of samples may be one possibility. This involves however, the risk that infrequent but possibly significant aberrations may be missed.Figures on http://www.esacp.org/acp/2000/20‐1/aubele.htm.
Automated Analysis of Protein Expression and Gene Amplification within the Same Cells of Paraffin-Embedded Tumour Tissue
Authors: Gaiser Timo , Berroa-Garcia Lissa , Kemmerling Ralf , Dutta Aparajita , Ried Thomas , Heselmeyer-Haddad Kerstin 
Published: January 2015

Background: The simultaneous detection of protein expression and gene copy number changes in patient samples, like paraffin-embedded tissue sections, is challenging since the procedures of immunohistochemistry (IHC) and Fluorescence in situ Hybridization (FISH) negatively influence each other which often results in suboptimal staining. Therefore, we developed a novel automated algorithm based on relocation which allows subsequent detection of protein content and gene copy number changes within the same cell.Methods: Paraffin-embedded tissue sections of colorectal cancers were stained for CD133 expression. IHC images were acquired and image coordinates recorded. Slides were subsequently hybridized with fluorescently labeled DNA probes. FISH images were taken at the previously recorded positions allowing for direct comparison of protein expression and gene copy number signals within the same cells/tissue areas. Relocation, acquisition of the IHC and FISH images, and enumeration of FISH signals in the immunophenotyped tumour areas were done in an automated fashion.Results: Automated FISH analysis was performed on 13 different colon cancer samples that had been stained for CD133; each sample was scored for MYC, ZNF217 and Chromosome 6 in CD133 positive and negative glands. From the 13 cases four (31%) showed amplification for the MYC oncogene and seven of 13 (54%) cases were amplified for ZNF217. There was no significant difference between CD133 positive tumour and CD133 negative tumour cells.Conclusion: The technique and algorithm presented here enables an easy and reproducible combination of IHC and FISH based on a novel automated algorithm using relocation and automated spot counting.
Glioblastomas with Oligodendroglial Component – Common Origin of the Different Histological Parts and Genetic Subclassification
Authors: Klink Barbara , Schlingelhof Ben , Klink Martin , Stout-Weider Karen , Patt Stephan , Schrock Evelin 
Published: January 2015

Background: Glioblastomas are the most common and most malignant brain tumors in adults. A small subgroup of glioblastomas contains areas with histological features of oligodendroglial differentiation (GBMO). Our objective was to genetically characterize the oligodendroglial and the astrocytic parts of GBMOs and correlate morphologic and genetic features with clinical data.Methods: The oligodendroglial and the “classic” glioblastoma parts of 13 GBMO were analyzed separately by interphase fluorescence in situ hybridization (FISH) on paraffin sections using a custom probe set (regions 1p, 1q, 7q, 10q, 17p, 19q, cen18, 21q) and by comparative genomic hybridization (CGH) of microdissected paraffin embedded tumor tissue.Results: We identified four distinct genetic subtypes in 13 GBMOs: an “astrocytic” subtype (9/13) characterized by +7/−10; an “oligodendroglial” subtype with −1p/−19q (1/13); an “intermediate” subtype showing +7/−1p (1/13), and an “other” subtype having none of the former aberrations typical for gliomas (2/13). The different histological tumor parts of GBMO revealed common genetic changes in all tumors and showed additional aberrations specific for each part.Conclusion: Our findings demonstrate the monoclonal origin of GBMO followed by the development of the astrocytic and oligodendroglial components. The diagnostic determination of the genetic signatures may allow for a better prognostication of the patients.
High Frequency Microsatellite Instability Has a Prognostic Value in Endometrial Endometrioid Adenocarcinoma, But Only in FIGO Stage 1 Cases
Authors: Steinbakk Anita , Malpica Anais , Slewa Aida , Gudlaugsson Einar , Janssen Emiel A. M. , Arends Mark , Kruse Arnold Jan , Yinhua Yu , Feng Weiwei , Baak Jan P. 
Published: January 2015

Objectives: To analyze the prognostic value of microsatellite instability (MSI) in a population-based study of FIGO stage 1–4 endometrial endometrioid adenocarcinomas.Study Design: Survival analysis in 273 patients of MSI status and clinico-pathologic features. Using a highly sensitive pentaplex polymerase chain reaction to establish MSI status, cases were divided into microsatellite stable (MSS), MSI-low (MSI-L, 1 marker positive) and MSI-high (MSI-H, 2–5 markers positive).Results: After 61 months median follow-up (1-209), 34 (12.5%) of the patients developed metastases but only 6.4% of the FIGO 1. MSI (especially as MSI-H vs. MSS/MSI-Lcombined) was prognostic in FIGO 1 but not in FIGO 2–4. The 5 and 10 year recurrence-free survival rates were 98% and 95% in the MSS/MSI-L vs. 85% and 73% in the MSI-H patients (p=0.005).Conclusions: MSI-H status assessed by pentaplex polymerase chain reaction is an indicator of poor prognosis in FIGO 1, but not in FIGO 2–4 endometrial endometrioid adenocarcinomas.
Role of Pituitary Tumour Transforming Gene 1 in Medullary Thyroid Carcinoma
Authors: Zatelli Maria Chiara , Tagliati Federico , Amodio Vincenzo , Buratto Mattia , Pelizzo Mariarosa , Pansini Giancarlo , Bondanelli Marta , Ambrosio Maria Rosaria , Uberti Ettore C. degli 
Published: January 2015

Background: Pituitary tumour transforming gene 1 (PTTG1) is over-expressed in a variety of endocrine-related tumours. We aimed at evaluatingPTTG1expression and function in human neoplastic parafollicular C-cells, represented by medullary thyroid carcinoma (MTC) and C-cell hyperplasia (CCH) samples and by the TT cell line.Methods: TT cells and tissues derived from human CCH (8 samples) and MTC (12 samples) were analyzed by northern blot, furthermore TT cells were subjected to PTTG gene silencing and cells were analyzed for DNA synthesis.Results:PTTG1expression was significantly higher (p< 0.01) in CCH (3-fold), in papillary thyroid cancer and in MTC (5-fold) than in normal thyroid, and in MTC lymph-node metastases as compared to primary lesions (~2-fold; p < 0.05).PTTG1mRNA and protein correlated with tumour diameter and TNM status (p < 0.05). In TT cells,PTTG1silencing did not completely block DNA synthesis, but significantly reduced [3H]Thymidine incorporation (~50%; p < 0.01) for up to 3 days.Conclusion:PTTG1levels correlate with tumour aggressiveness.PTTG1silencing causes reduced MTC cell proliferation, supporting the hypothesis thatPTTG1might have an important role in C-cell neoplastic proliferation.
Immunohistochemical Expression and Localization of Somatostatin Receptor Subtypes in Androgen Ablated Prostate Cancer
Authors: Mazzucchelli Roberta , Morichetti Doriana , Santinelli Alfredo , Scarpelli Marina , Bono Aldo V. , Lopez-Beltran Antonio , Cheng Liang , Montironi Rodolfo 
Published: January 2015

Objective: The aim was to examine the expression and localization of the five somatostatin receptors (termed SSTR1–5) in radical prostatectomies (RPs) from patients with prostatic adenocarcinoma (PCa) under complete androgen ablation (CAA) before operation.Material: The five SSTRs were evaluated in the epithelial, smooth muscle and endothelial cells of normal-looking epithelium (Nep), high-grade prostatic intraepithelial neoplasia (HGPIN) and PCa in 20 RPs with clinically detected PCa from patients under CAA. 20 RPs with clinically detected PCa from hormonally untreated patients were used as control group.Results: Concerning the secretory cells (i) membrane staining was seen for SSTR3 and SSTR4; the mean percentages of positive cells, higher in SSTR3 than in SSTR4, decreased sharply in HGPIN and PCa compared with Nep; the mean percentages in the androgen ablated group were 30–90% lower than in the untreated; (ii) cytoplasmic staining was seen for all 5 SSTRs; the mean percentages of positive cells in Nep, HGPIN and PCa of the untreated group were similar, and in general as high as 80% or more; in the treated group, the Nep values were similar to those in the untreated, whereas the values in HGPIN and PCa were lower for SSTR1, 3 and 5, with a decrease of 30% for SSTR1; (iii) nuclear staining was seen with SSTR4 and SSTR5, the mean percentages for the former being much lower than for the latter; treatment affected both HGPIN and PCa, whose proportions of stained cells were 30–55% lower than in the untreated group. Cytoplasmic staining in the basal cells was seen for all 5 SSTRs, both in Nep and HGPIN. The values in the treated group were lower than in the other, the difference between the two group being in general comprised between 10 and 40%. Treatment did not affect SSTR staining in the smooth muscle and endothelial cells.Conclusions: The present study expands our knowledge on the expression and localization of the five SSTRs in the prostate following CAA.
ESR1 Amplification is Rare in Breast Cancer and is Associated with High Grade and High Proliferation: A Multiplex Ligation-Dependent Probe Amplification Study
Authors: Moelans Cathy B. , Monsuur Hanneke N. , de Pinth Johannes H. , Radersma Remco D. , de Weger Roel A. , van Diest Paul J. 
Published: January 2015

Background: Expression of estrogen receptor alpha (ERα) is predictive for endocrine therapy response and an important prognostic factor in breast cancer. Overexpression of ERα can be caused by estrogen receptor 1 (ESR1) gene amplification and was originally reported to be a frequent event associated with a significantly longer survival for ER-positive women treated with adjuvant tamoxifen monotherapy, which was however questioned by subsequent studies.Methods: This study aimed to reanalyze the frequency of ESR1 amplification by multiplex ligation-dependent probe amplification (MLPA) and fluorescence in situ hybridisation (FISH), and to assess clinicopathologic correlations. MLPA was performed in a group of 135 breast cancer patients, and gains/amplifications were subjected to FISH.Results: True ESR1 amplification by MLPA was rare (2%) and only 6% more patients showed a modest gain of ESR1. All MLPA-detected ESR1 amplifications and nearly all ESR1 gains were also FISH amplified and gained, but not all FISH amplifications/gains were MLPA amplified/gained, leading to an overall concordance of only 60% between both techniques. All 3 MLPA and FISH ESR1 amplified cases had high ERα expression, but there was no obvious correlation between ESR1 gain and ER status by IHC. ESR1 gains/amplifications were not associated with HER2 gain/amplification, but seemed to be associated with older age. Surprisingly, ESR1 gain/amplification was not associated with low grade as reported previously, but correlated with high grade and high proliferation. Furthermore, ESR1 gain/amplification by MLPA was not associated with nodal status or tumor size (pT status).Conclusion: ESR1 amplification as detected by MLPA is rare in breast cancer, and seems to be associated with high ERα expression, high age, high grade and high proliferation. This study confirms previous studies that showed differences in the ESR1 amplification frequencies detected by different techniques.