bluuebunny/crossref_metadata_2025 huggingface dataset:
Microsatellite allelotyping differentiates chromophobe renal cell carcinomas from renal oncocytomas and identifies new genetic changes
Authors: Nagy A , Buzogany I , Kovacs G
Published: December 2004

Aims:  The diagnosis of renal oncocytomas (ROs) and chromophobe renal cell carcinomas (RCCs) based on histological features is often uncertain. To assess the value of genetic analysis in their differential diagnosis we analysed 27 ROs and 21 chromophobe RCCs by microsatellite allelotyping.

Methods and results:  Markers at the short and long arms of chromosomes specifically involved in the genetic changes of the four main types of renal cancers were selected. Allelic changes were identified by automated sequencing. Allelic changes at chromosome 1p occurred in 8/26 (31%) and at chromosome 14q in 4/27 (15%) ROs. Loss of heterozygosity (LOH) at chromosomes 1, 2, 6, 10, 13, 17 and 21 were seen in 90%, 90%, 96%, 86%, 85%, 90% and 72% of the chromophobe RCCs, respectively. Alterations of at least three of these chromosomal sites were detected in each chromophobe RCC. In addition, we found recurrent LOH at chromosomes 9p23 (43%), 18q22 (30%), 5q22 (28%) and 8p (28%) in chromophobe RCCs.

Conclusions:  Chromophobe RCCs can be differentiated from ROs by analysing specific chromosomal regions with microsatellites.
British Division of the International Academy of Pathology
Authors: Van Den Tweel J , Howat A J , Shepherd N A , Francis N , Harris C
Published: December 2004

Forthcoming meetings

Spring 2004 Symposium on Dermatopathology. Brussels, Belgium

10–15 October 2004 XXVth International Congress. Brisbane, Australia

26–27 November 2004 Symposium on Pulmonary Pathology. London, UK
Histological indicators of prognosis in glioblastomas: retinoblastoma protein expression and oligodendroglial differentiation indicate improved survival
Authors: Hilton D A , Penney M , Pobereskin L , Sanders H , Love S
Published: December 2004

Aim:  To assess the potential prognostic significance of a range of molecular and morphological parameters in glioblastomas that can be applied in the setting of a routine diagnostic neuropathology laboratory.

Methods and results:  A consecutive series of 107 adult glioblastomas were studied. Retinoblastoma and deleted‐in‐colon cancer (DCC) protein expression were assessed using immunocytochemistry and chromosome 10 loss by in‐situ hybridization. Loss of retinoblastoma expression was associated with a worse outcome, which appeared to be independent of age. There was no significant association between chromosome 10 loss or DCC protein expression and survival. Survival was significantly increased in the 5% of patients whose tumours had focal morphological features suggesting oligodendroglial differentiation.

Conclusions:  Glioblastomas containing areas of oligodendroglial differentiation or showing widespread immunocytochemical expression of retinoblastoma protein have a better prognosis than those without these features.
Human telomerase catalytic subunit gene re‐expression is an early event in oral carcinogenesis
Authors: Luzar B , Poljak M , Marin I J , Eberlinc A , Klopčič U , Gale N
Published: December 2004

Aims:  Detection of telomerase catalytic subunit (hTERT) mRNA has been used as a surrogate marker for estimation of telomerase activity. The exact role and timing of telomerase re‐activation, a key enzyme implicated in cellular immortalization and transformation, in the multistep process of oral carcinogenesis is still unknown. The aim was to test the hypothesis that (i) quantitative rather than qualitative differences exist in the level of hTERT mRNA expression between normal oral mucosa, different grades of oral epithelial abnormalities and squamous cell carcinomas of the oral cavity, and that (ii) hTERT gene re‐expression is an important, probably early event in oral carcinogenesis.

Methods and results:  The relative quantity of hTERT mRNA was analysed in 45 frozen oral epithelia representing different morphological stages of oral carcinogenesis classified according to the Ljubljana classification and in 37 oral squamous cell carcinomas, using a commercially available LightCycler Telo TAGGG hTERT Quantification kit. hTERT mRNA was not detected in normal or reactive hyperplastic oral epithelia, but was present in 43% of atypical hyperplasias (premalignant lesions), 60% of intraepithelial carcinomas and 68% of oral squamous cell carcinomas. Statistical analysis revealed two groups of oral epithelial changes, with significant differences in the levels of hTERT mRNA expression: 1, normal and reactive hyperplastic oral epithelium, and 2, atypical hyperplasia, intraepithelial carcinomas and squamous cell carcinomas.

Conclusion:  These data suggest that hTERT gene re‐expression represents an early event in the multistep process of oral carcinogenesis, already detectable at the stage of precancerous oral epithelial changes. Nevertheless, other genetic aberrations appear to be necessary for progression of oral epithelial abnormalities towards invasive squamous cell carcinoma.
DNA ploidy analysis in histopathology
Authors: Baak J P A , Janssen E
Published: December 2004

The introduction of new technologies, designed to assess biologically relevant alterations in tumour cells, has the potential to provide additional prognostic and predictive information from biopsies, as well as providing a more objective assessment than conventional histopathology alone. One such technique is the assessment of the ploidy status of tumours. DNA ploidy studies, using various technologies, are abundant in the literature, but questions remain as to how such studies should be translated into evidence‐based practice. In this Expert Opinion, we provide two perspectives on this field. Baak and Janssen discuss the technology and set the assessment of ploidy in the context of other quantitative techniques. Clinical applications are then illustrated. In the paper by Peter Hall, aspects of the biology of ploidy are discussed, and the potential relevance of a more detailed understanding of the biology of ploidy to clinical application. Some of the general short‐comings of the applied literature are discussed and some approaches suggested for the improvement of the evidence base on which healthcare decisions relating to the application of new technologies are made.
Cyclooxygenase 2 (COX2) expression is associated with poor outcome in ER‐negative, but not ER‐positive, breast cancer
Authors: Witton C J , Hawe S J K , Cooke T G , Bartlett J M S
Published: December 2004

Aims:  Inflammation and hormonal signalling induce cyclooxygenase 2 (COX2) expression in solid tumours. COX2 expression is linked to neovascularization and tumour growth. HER2 modulates colorectal cancer COX2 expression. We investigated interactions between COX2 and HER1–4 in breast cancer.

Methods and results:  COX2 expression was localized to epithelial cells with 21.2% of cases expressing higher levels than normal epithelium. Elevated COX2 expression was not associated with size, grade, high Nottingham prognostic index (NPI) or oestrogen receptor (ER) negativity. No association was observed between COX2 and HER1–4 expression. High COX2 expression was associated with reduced disease‐free survival (P = 0.03) and disease‐related survival in ER‐negative (P = 0.046) but not ER‐positive disease (P = 0.835).

Conclusion:  HER1, 2, 3 and 4 are not associated with high breast tumour COX2 expression. COX2 is frequently expressed in breast carcinoma cells and adjacent epithelium. COX2 may be an important factor in promoting tumour progression in ER‐negative tumours and a potential drug target in breast tumours.
p57KIP2 immunohistochemical staining of gestational trophoblastic tumours does not identify the type of the causative pregnancy
Authors: Sebire N J , Rees H C , Peston D , Seckl M J , Newlands E S , Fisher R A
Published: December 2004

Aim:  To determine whether immunohistochemical staining for p57KIP2, the product of the maternally expressed gene CDKN1C, can be used to differentiate between gestational trophoblastic tumours arising from a complete hydatidiform mole and those originating from non‐molar pregnancies.

Methods:  The immunohistochemical expression of p57KIP2 was investigated in 23 cases of choriocarcinoma and 17 placental site trophoblastic tumours. Fourteen of the tumours examined were shown by DNA analysis to have arisen from complete hydatidiform moles and 26 from non‐molar pregnancies.

Results:  Five of 11 (45%) post‐complete hydatidiform mole choriocarcinomas and two of three (67%) post‐complete hydatidiform mole placental site trophoblastic tumours were found to be p57KIP2+ and showed similar immunostaining characteristics to tumours that developed from non‐molar pregnancies. Although there was a statistically significant reduction in the proportion of cases showing positive p57KIP2 staining in post‐complete hydatidiform mole tumours compared with those originating in non‐molar pregnancies {proportion difference 0.35 [95% confidence interval (CI) 0.05, 0.61], P = 0.02}, immunostaining did not provide diagnostically useful information to differentiate between these tumours in clinical practice. There was no significant difference between the extent of staining in choriocarcinoma versus placental site trophoblastic tumours [proportion difference 0.17 (95% CI − 12, 42), P = 0.19]. The majority of both types of gestational trophoblastic tumour were positive for the presence of the p57KIP2 protein irrespective of their genetic origin.

Conclusion:  Immunostaining for p57KIP2 fails to discriminate between gestational trophoblastic tumours that have arisen from complete hydatidiform moles and those that have originated from other types of pregnancy.
Microscopic colitis with granulomatous inflammation
Authors: Saurine T J , Brewer J M , Eckstein R P
Published: December 2004

Aims:  To present four cases in which the clinical and endoscopic findings were consistent with microscopic colitis, but the inflammatory infiltrate included a conspicuous granulomatous reaction. Microscopic colitis is defined as a syndrome of chronic watery diarrhoea with a chronic inflammatory cell infiltrate in the colonic mucosa and without significant abnormalities at colonoscopy. It encompasses both collagenous and lymphocytic colitis.

Methods and results:  In all cases the clinical course and endoscopic findings were unlike Crohn's disease and no infectious agents were identified. In all cases the main symptom was frequent watery diarrhoea, all were female and there were no endoscopic findings apart from mild mucosal erythema. Histologically, an active chronic inflammatory infiltrate was accompanied by scattered non‐necrotizing granulomas, often closely associated with crypt epithelium (cryptolytic or pericryptal granulomas). In three of the patients the symptoms began after antibiotic use or had worsened with antibiotic use. Two of the patients were on allopurinol at the time of the onset of symptoms. In two of the patients symptoms have continued for more than 10 years. One patient died as a result of medical complications relating to severe diarrhoea and dehydration.

Conclusions:  Microscopic colitis rarely may be characterized by granulomatous inflammation. Such patients should not be regarded as having Crohn's disease.
Immunohistochemical screening for β6‐integrin subunit expression in adenocarcinomas using a novel monoclonal antibody reveals strong up‐regulation in pancreatic ductal adenocarcinomas in vivo and in vitro
Authors: Sipos B , Hahn D , Carceller A , Piulats J , Hedderich J , Kalthoff H , Goodman S L , Kosmahl M , Klöppel G
Published: December 2004

Aims : To analyse the expression of αvβ6, an epithelial integrin involved in wound healing and tumorigenesis, in various human carcinoma types.

Methods and results : A new monoclonal antibody to the human β6 subunit, 5C4, was used to locate αvβ6 in 157 cancers of gastroenteropancreatic and 21 of lung origin. The data were validated by analysis of αvβ6 extracted from histological sections. αvβ6 integrin showed strongest expression in 34 pancreatic ductal adenocarcinomas (mean score 2.88 ± 0.52), followed by 24 intestinal‐type gastric carcinomas (1.45 ± 1.06) and eight lung adenocarcinomas (1.37 ± 1.1). Moderate expression was found in 31 diffuse‐type gastric carcinomas (0.94 ± 0.83), seven duodenal adenocarcinomas (0.8 ± 1.34) and 26 colorectal adenocarcinomas (0.76 ± 0.71). Little αvβ6 was seen in seven liver cell carcinomas and six neuroendocrine tumours. Well‐differentiated carcinomas expressed more β6 than poorly differentiated tumours. Peritumoral epithelial tissues where αvβ6‐expressing tumours arose also expressed αvβ6. There was no correlation between expression of αvβ6 and its ligands tenascin and fibronectin in pancreatic and gastric carcinomas. Spheroid formation by pancreatic carcinoma cell lines led to αvβ6 up‐regulation, but appeared independent of classical ligand binding to αvβ6.

Conclusions : Our findings indicate that: (i) αvβ6 is overexpressed in pancreatic adenocarcinomas; (ii) αvβ6‐positive carcinomas originate from αvβ6‐expressing tissues; (iii) αvβ6 expression in tumours seems to be regulated independently from that of its ligands tenascin and fibronectin; and (iv) in‐vitro overexpression of αvβ6 in pancreatic carcinoma cell lines accompanies spheroid formation.
Desquamative interstitial pneumonia, respiratory bronchiolitis and their relationship to smoking
Authors: Craig P J , Wells A U , Doffman S , Rassl D , Colby T V , Hansell D M , Du Bois R M , Nicholson A G
Published: December 2004

Aims : Respiratory bronchiolitis (RB) and desquamative interstitial pneumonia (DIP) are closely associated histological patterns of interstitial pneumonia, although there are no studies on the extent of individual histological parameters. Furthermore, the term smoking related‐interstitial lung disease (SR‐ILD) has been proposed as a term to encompass patients with both these histological patterns who give a history of smoking, though it is not well defined how this term relates to historical cases of DIP. The aim of this study was to compare histological parameters in cases of DIP and RB and then to review in detail clinical, imaging and histological data for DIP in relation to a history of smoking.

Methods and results : Forty‐nine cases were reviewed, 24 with RB and 25 with DIP; five cases of DIP were re‐classified as RB on review due to bronchocentricity of the infiltrate. There was a significantly greater extent of interstitial fibrosis (P = 0.02), lymphoid follicles (P < 0.001) and eosinophilic infiltration (P < 0.0001) in patients with DIP compared with RB. In addition, the extents of these three parameters were significantly interrelated. Patients with DIP had a lower incidence of smoking (60%) when compared with patients with RB‐ILD (93%) (P < 0.005). Further analysis of smokers versus never‐smokers with DIP showed no difference in histological parameters, extent of haemosiderin deposition or the number of CD1a+ macrophages between the two groups, nor were there any differences in clinical data to suggest other aetiologies. Follow‐up high‐resolution computed tomography data from patients with DIP suggested that a pattern of fibrotic non‐specific interstitial pneumonia (NSIP) may develop in the long term in both smokers and never‐smokers.

Conclusion : There are significant differences in the extent of interstitial fibrosis, lymphoid follicles and eosinophilic infiltration between DIP and RB, as well as a much lower incidence of smoking in patients with DIP. Whether the lower reported incidence of smoking in DIP reflects referral bias or conservatism in giving a history of smoking remains uncertain, as neither histological parameters nor clinical data indicate a difference between smokers and never‐smokers with DIP. Nevertheless, some cases of DIP are likely to remain idiopathic and unrelated to RB, though still have a good prognosis. Furthermore, they may evolve into a pattern resembling fibrotic NSIP. Therefore, whilst SR‐ILD is appropriate in the correct clinical setting, the distinction between the histological patterns of RB and DIP remains appropriate.
Survivin expression is a negative prognostic marker in laryngeal squamous cell carcinoma and is associated with p53 accumulation
Authors: Pizem J , Cör A , Gale N
Published: December 2004

Aims:  To investigate survivin expression in laryngeal squamous cell carcinoma (LSCC), its prognostic significance and relation to p53 status. Survivin is an inhibitor of apoptosis protein that is overexpressed in cancer. It has been implicated in both prevention of apoptosis and cell cycle regulation. It has been suggested that wild‐type p53 represses survivin expression.

Methods and results:  Expression of survivin and p53 was analysed in 68 archival biopsy specimens of LSCC by immunohistochemistry. Survivin was detected in 67 of 68 LSCC cases; the proportion of survivin‐positive cells varied from 8.2% to 100%. It was localized in the nucleus and/or cytoplasm of tumour cells. Of LSCC cases, 31.8% were p53+. The number of survivin‐positive cells was significantly higher in the p53+ group. A high level of survivin expression and a supraglottic site of the tumour were two independent adverse prognostic factors in LSCC.

Conclusions:  Survivin is expressed in a varying proportion of cells in virtually all cases of LSCC. A high level of its expression predicts poor survival. Loss of wild‐type p53 is a possible mechanism of survivin up‐regulation in LSCC.
Alpha‐methylacyl‐CoA racemase: a multi‐institutional study of a new prostate cancer marker
Authors: Jiang Z , Wu C L , Woda B A , Iczkowski K A , Chu P G , Tretiakova M S , Young R H , Weiss L M , Blute R D , Brendler C B , Krausz T , Xu J C , Rock K L , Amin M B , Yang X J
Published: December 2004

Aim : To test whether α‐methylacyl‐CoA racemase (AMACR) is a sensitive and specific marker of prostate cancer.

Methods and results : The expression levels of AMACR mRNA were measured by real‐time polymerase chain reaction. A total of 807 prostatic specimens were further examined by immunohistochemistry specific for AMACR. Quantitative immunostaining analyses were carried out by using the ChromaVision Automated Cellular Imaging System and the Ariol SL‐50 Imaging System, respectively. AMACR mRNA levels measured in prostatic adenocarcinoma were 55 times higher than those in benign prostate tissue. Of 454 cases of prostatic adenocarcinoma, 441 were positive for AMACR, while 254 of 277 cases of benign prostate were negative for AMACR. The sensitivity and specificity of AMACR immunodetection of prostatic adenocarcinomas were 97% and 92%, respectively. Both positive and negative predictive values were 95%. By automatic imaging analyses, the AMACR immunostaining intensity and percentage in prostatic adenocarcinomas were also significantly higher than those in benign prostatic tissue (105.9 versus 16.1 for intensity, 45.7% versus 0.02% and 35.03% versus 4.64% for percentage, respectively).

Conclusions : We have demonstrated the promising features of AMACR as a biomarker for prostate cancer in this large series and the potential to develop automated quantitative diagnostic tests.
Nasopharyngeal intraepithelial lesion: latent Epstein–Barr virus infection with malignant potential
Authors: Cheung F M F , Pang S W , Yau T K , Chow S K , Lo K W
Published: December 2004

Aims:  To study the morphology and immunohistochemical expression of nasopharyngeal intraepithelial lesions and to understand their place in nasopharyngeal carcinogenesis.

Methods and results:  Nine cases of nasopharyngeal intraepithelial lesion (NPIL) were diagnosed during nasopharyngeal biopsy screening for nasopharyngeal carcinoma (NPC). Two cases were associated with early invasion. All cases demonstrated specific histological features and consistent positivity on in‐situ hybridization for Epstein–Barr virus (EBV)‐encoded RNA. Pure NPIL lesions showed low‐grade morphology while lesions associated with early invasion were high grade. Immunohistochemical studies showed increased expression of bcl‐2 and essentially negative findings for BZLF1 and LMP1. High‐grade lesions had relatively stronger expression of bcl‐2 and p53.

Conclusions:  NPIL harbours latent EBV infection and has malignant potential. Multiple steps are involved in its occurrence and progression. Low‐grade and high‐grade lesions should be managed differently.
Morphological and immunohistochemical analysis of ductal plate malformation: correlation with fetal liver
Authors: Awasthi A , Das A , Srinivasan R , Joshi K
Published: December 2004

Aims : Ductal plate malformation (DPM) is the persistence of excess of embryonic bile duct structures in the portal tracts. Most of the congenital diseases of intrahepatic bile ducts represent examples of DPM at different levels of the biliary tree. The aim of the present study was to evaluate the histopathological spectrum and immunohistochemical properties of DPM in various paediatric liver diseases and compare them with those of the normal embryonic ductal plates of human fetuses.

Methods and results : All paediatric liver biopsies and autopsied livers of infant deaths and stillbirths over a 5‐year period (between 1996 and June 2001) were subjected to histopathological examination to identify ductal plate malformations. A detailed immunohistochemical analysis was carried out in 35 cases of ductal plate malformation and 25 abortuses by using antibodies against cytokeratin (CK)7, 8, 18 and 19, CD34 and type IV collagen. Thirty‐nine cases of ductal plate malformation were identified which consisted of extrahepatic biliary atresia with DPM (n = 20), isolated congenital hepatic fibrosis (n = 9), autosomal recessive polycystic kidney disease (n = 5), congenital hepatic fibrosis with autosomal polycystic kidney disease (n = 2), Caroli's syndrome (n = 2) and one case of Ivemark's syndrome. The ductal plate cells stained with CK7, 8, 18 and 19 but not with CD34.

Conclusion : DPM was present in all intrahepatic bile duct diseases included in this study and in about 26% of cases of extrahepatic biliary atresia. The cytokeratin immunophenotype of the ductal plate in pathological conditions is similar to that of normal embryonic ductal plates of fetuses after 20 weeks of gestation.
Prognostic analysis of pulmonary adenocarcinoma subclassification with special consideration of papillary and bronchioloalveolar types
Authors: Aida S , Shimazaki H , Sato K , Sato M , Deguchi H , Ozeki Y , Tamai S
Published: December 2004

Aims: The third edition of the World Health Organization (WHO) classification of lung tumours has been published and is expected to become the standard nomenclature. The aim of this study was to assess the usability and prognostic significance of the WHO classification in comparison with other recent classifications.

Methods and results: One hundred and forty‐seven resected pulmonary adenocarcinoma cases were reviewed and histologically classified according to the WHO classification (1999) and the classification by Noguchi (1995). Papillary carcinomas as described by Silver and Askin (1997) were also identified. Since the papillary type in the WHO classification is not strictly defined, we compared the following two kinds of WHO classification: (i) WHO‐N; WHO classification adopting Noguchi Type F as the definition of the papillary type, namely, pure papillary adenocarcinoma without a bronchioloalveolar component; (ii) WHO‐SA; WHO classification adopting papillary carcinoma by Silver and Askin as the definition of the papillary type, namely, tumour with papillary structure constituting at least 75% of the lesion. The bronchioloalveolar carcinoma of the WHO classification showed a better prognosis than other subtypes in both overall and Stage I disease limited survival analysis. In analysis limited to Stage III disease, only the papillary type of WHO‐SA showed a significantly worse prognosis.

Conclusions: WHO‐SA is recommended for prognostic correlation.
Ductal carcinoma in situ with spindle cells: a potential diagnostic pitfall in the evaluation of breast lesions
Authors: Tan P H , Lui G G , Chiang G , Yap W M , Poh W T , Bay B H
Published: December 2004

Aims : To evaluate the morphological features of 11 cases of breast ductal carcinoma in situ (DCIS) with spindle cells and to propose an approach to distinguish it from benign mimics. The association with neuroendocrine differentiation was also investigated.

Methods : Cases of breast DCIS with a spindle cell component diagnosed in the Department of Pathology, Singapore General Hospital, between June 1996 and January 2003, were included in the study. The histological characteristics were documented, and immunohistochemistry for neuroendocrine markers, hormone receptors, cerbB2, smooth muscle actin (SMA) and high‐molecular‐weight (HMW) cytokeratins, was carried out. Electron microscopy was carried out on reprocessed paraffin‐embedded material in three cases.

Results : Of 11 women diagnosed with DCIS with spindle cells, four presented with nipple discharge, six with a breast lump, while one was discovered to have a screen detected density. The tumour size ranged from 3 to 41 mm. The proportion of spindle cells varied from 10% to 80% of the in‐situ tumour cell population. Nuclear grade was low in seven cases and intermediate in four. Necrosis was observed in two cases. Architectural pattern was papillary in six cases, and mixed in the rest. Microinvasion was present in two cases, with possible microinvasion in another two. Immunohistochemistry for neuroendocrine markers synaptophysin and chromogranin showed positive reactivity for at least one marker in all but three cases; one of these latter cases demonstrated ultrastructural neurosecretory granules. Oestrogen and progesterone receptors were expressed in 10 and nine cases, respectively, while cerbB2 was positive in only one case. HMW cytokeratin immunoprofile revealed a general lack of immunostaining within the abnormal cell population; likewise, no positivity for SMA of the cellular proliferation was detected.

Conclusions : Almost all DCIS lesions with spindle cells disclose neuroendocrine differentiation. Although the distinction from benign florid usual hyperplasia may pose a diagnostic histological problem, the presence of diffuse neuroendocrine expression, in conjunction with the pattern of HMW keratin profile on immunohistochemistry, supports an in‐situ neoplastic process. The absence of SMA immunostaining, in conjunction with negative reactivity for cytokeratins 5/6 and 14, makes the possibility of a myoepithelial proliferation unlikely.
British Division of the International Academy of Pathology
Authors: Van Den Tweel J , Howat A J , Shepherd N A , Francis N , Harris C
Published: December 2004

10–15 October 2004 XXVth International Congress. Brisbane, Australia

26–27 November 2004 Symposium on Pulmonary Pathology. London, UK

5–8 July 2005 Joint Meeting with the Pathological Society of Great Britain and Ireland. Newcastle‐Upon‐Tyne, UK

25–26 November 2005 Symposium on Intestinal Pathology. London, UK
Rare expression of KIT (CD117) in lymphomas: a tissue microarray study of 1166 cases
Authors: Zimpfer A , Went P , Tzankov A , Pehrs A‐C , Lugli A , Maurer R , Terracciano L , Pileri S , Dirnhofer S
Published: December 2004

Aims : Imatinib mesylate specifically inhibits KIT tyrosine kinase activity, and has been proven to be effective in the treatment of gastrointestinal stromal tumours. Because other KIT‐expressing malignancies might benefit from Imatinib therapy, we evaluated the distribution and expression of KIT in 1166 cases of malignant lymphoma.

Materials and results : Tissue microarrays (TMAs) containing 824 non‐Hodgkin's lymphoma (NHL) and 342 Hodgkin's lymphoma (HL) cases were immunohistochemically analysed for the expression of the KIT protein. Two KIT‐positive NHLs were sequenced using polymerase chain reaction analysis. One T‐cell lymphoma and one follicular lymphoma of the 747 NHL cases (0.3%) were positive for KIT. All HLs were Kit‐negative. None of the KIT‐positive cases showed a kit gene mutation.

Conclusions : KIT expression is a very rare event in NHL and virtually absent in HL. In the few positive cases, the aberrant expression is not caused by a mutation in the ‘hot‐spots’ of the kit gene, indicating that treatment of these tumours with Imatinib may be ineffective.
Dermal dendritic melanocytic proliferations: an update
Authors: Zembowicz A , Mihm M C
Published: December 2004

Dermal dendritic melanocytic proliferations are a broad group of congenital and acquired melanocytic lesions characterized by the presence of dermal spindled and dendritic cells resembling melanocytes migrating from the neural crest to the epidermis. Historically, they were subdivided into dermal melanocytoses (naevus of Ota, Ito, Mongolian spot and related conditions), blue naevi and malignant blue naevi. The purpose of this review is to provide an update on recent developments in the field with emphasis on new entities and their differential diagnosis.
Tenascin‐C in primary malignant melanoma of the skin
Authors: Ilmonen S , Jahkola T , Turunen J P , Muhonen T , Asko‐Seljavaara S
Published: December 2004

Aims : To investigate the expression and the prognostic role of glycoprotein Tenascin‐C (Tn‐C) in primary melanoma of the skin.

Methods and results : The immunohistochemical expression of Tn‐C was studied in 98 primary melanomas and related to inflammation, invasion, and patient outcome. Patients were followed up for disease recurrence for 0.04–7.4 years (median 3.9) and for survival for 0.5 to 12.1 years (median 9.3). The expression of Tn‐C was evaluated for each tumour invasion border; the stromal and intracytoplasmic Tn‐C of the melanoma islets were also recorded. Tn‐C is widely expressed in primary melanoma samples, the staining pattern varying from focal to diffuse in different parts of the tumour. No correlation existed between intensity of Tn‐C staining and inflammation. No stromal Tn‐C was detected at the upper dermal lateral border in 12 patients, nor at the deep, dermal or subcutaneous border in 14 patients. These patients showed better disease‐free survival (DFS) than did those cases with focal or diffuse staining (P = 0.06, P = 0.05). Also, absence of intracytoplasmic Tn‐C was a beneficial prognostic factor for DFS (P = 0.04). In multivariate analysis, tumour ulceration and intracytoplasmic Tn‐C expression of melanoma cells were independent adverse prognostic factors for DFS.

Conclusions : In primary melanoma of the skin, absence of Tn‐C in the stroma of invasion fronts and within tumour cells seems to be related to a more benign disease behaviour with a lower risk of developing metastases.
British Division of the International Academy of Pathology
Authors: Van Den Tweel J , Howat A J , Shepherd N A , Francis N , Harris C
Published: December 2004

Forthcoming meetings

10–15 October 2004 XXVth International Congress. Brisbane, Australia 26–27 November 2004 Symposium on Pulmonary Pathology. London, UK 5–8 July 2005 Joint Meeting with the Pathological Society of Great Britain and Ireland. Newcastle‐Upon‐Tyne, UK 25–26 November 2005 Symposium on Intestinal Pathology. London, UK
Galectin‐3 does not reliably distinguish benign from malignant thyroid neoplasms
Authors: Mehrotra P , Okpokam A , Bouhaidar R , Johnson S J , Wilson J A , Davies B R , Lennard T W J
Published: December 2004

Aims:  To determine whether galectin‐3 is a sensitive indicator of thyroid malignancy. It has been suggested as a potential marker for differentiating thyroid carcinoma from benign or non‐neoplastic lesions in preoperative fine‐needle aspirates (FNAs).

Methods:  Galectin‐3 protein expression was assessed by immunohistochemistry in formalin‐fixed thyroid tissues from 124 patients with histological diagnoses of papillary carcinoma (n = 38), follicular carcinoma (n = 19), follicular adenoma (n = 32) and dominant nodules of multinodular goitre (n = 35). Expression of galectin‐3 was also assessed by Western blotting in 24 fresh thyroid tissues.

Results:  Galectin‐3 expression was observed in the majority of carcinomas (papillary 92%; follicular 74%). However, a large proportion of follicular adenomas (72%) and multinodular goitres (57%) also expressed galectin‐3. In addition, galectin‐3 expression was observed in epithelial cells of normal thyroid tissue and Hashimoto's thyroiditis. Galectin‐3 immunopositivity was significantly greater in papillary carcinomas than in dominant nodules or follicular adenomas (P < 0.0001, P = 0.0005, respectively). However, galectin‐3 expression was no greater in follicular carcinomas than in follicular adenomas (P = 0.8735). Western blotting analysis confirmed both the specificity of the antiserum and expression of galectin‐3 in multinodular goitres, follicular adenomas/carcinomas and papillary carcinomas.

Conclusion:  The data demonstrate that galectin‐3 is not a reliable immunohistochemical marker to distinguish benign from malignant thyroid follicular lesions.
The pattern and frequency of t(14;18) translocation and immunophenotype in Asian follicular lymphoma
Authors: Peh S C , Shaminie J , Tai Y C , Tan J , Gan S S
Published: December 2004

Aims:  Follicular lymphoma is frequently associated with t(14;18)(q32;q21) translocation. This study was undertaken to determine the pattern of Bcl‐2, CD10 and Bcl‐6 expression in relation to t(14;18) translocation in follicular lymphoma from a cohort of a multi‐ethnic Asian population.

Methods and results:  Sixty‐two cases of follicular lymphoma were retrieved for immunohistochemistry, and t(14;18) translocation analysis by polymerase chain reaction and fluorescent in‐situ hybridization techniques. Bcl‐2 expression was present in 74% of the cases. CD10 expression was also relatively low (61%), with decreasing frequency of expression in high‐grade tumours. Bcl‐6 protein was expressed in most of the tumours (88%) regardless of the tumour grade. The t(14;18) translocation was detected in 46 cases (74%) with an extremely high rate of t(14;18) translocation in ethnic Indian cases (100%).

Conclusion:  The frequency of t(14;18) translocation in this series of follicular lymphomas was higher when compared with previous Asian reports, but in accordance with European and North American findings. CD10 expression is strongly associated with a t(14;18) translocation event, but the overall CD10 expression was relatively low, possibly due to the high proportion of high‐grade tumours in the series. t(14;18) translocation was not associated with Bcl‐2 or Bcl‐6 expression.
Antimicrobial activity of varying concentrations of sodium hypochlorite on the endodontic microorganisms Actinomyces israelii, A. naeslundii, Candida albicans and Enterococcus faecalis
Authors: Radcliffe C. E. , Potouridou L. , Qureshi R. , Habahbeh N. , Qualtrough A. , Worthington H. , Drucker D. B.
Published: December 2004

Aim  To determine the resistance of microorganisms associated with refractory endodontic infections to sodium hypochlorite used as a root canal irrigant.

Methodology  Two strains each of Actinomyces naeslundii, Candida albicans and Enterococcus faecalis were tested as late logarithmic phase inocula, against sodium hypochlorite adjusted to 0.5, 1.0, 2.5 and 5.25% w/v. Contact times used were 0, 10, 20, 30, 60 and 120 s. In the case of E. faecalis, additional experiments used contact times of 1.0, 2.0, 5.0, 10.0 and 30.0 min. Anti‐microbial action was halted by sodium thiosulphate addition. Survivors were measured primarily using viable counts on drop plates. Additionally, pour plates were used to count low colony‐forming units (cfu) and dilutions to 10−6 were used to count high cfu.

Results  All concentrations of NaOCl lowered cfu below the limit of detection after 10 s in the case of A. naeslundii and C. albicans. However, E. faecalis proved to be more resistant to NaOCl. Using 0.5% NaOCl for 30 min reduced cfu to zero for both strains tested. This compares with 10 min for 1.0%, 5 min for 2.5% and 2 min for 5.25% (P < 0.001). Regression analysis for the dependent variable loge(count + 1) with loge(time + 1) and concentration as explanatory variables gave rise to a significant interaction between time and concentration (P < 0.001).

Conclusion  The published association of E. faecalis with refractory endodontic infection may result, at least partially, from high resistance of this species to NaOCl. This does not appear to be the case with A. naeslundii or C. albicans.
Effect of root‐end resection and root‐end filling on apical leakage in the presence of core‐carrier root canal obturation
Authors: Taschieri S. , Del Fabbro M. , Francetti L. , Testori T.
Published: December 2004

Aim  To evaluate the apical seal of canals filled with a core‐carrier obturator following root‐end resection with and without a root‐end filling.

Methodology  Thirty single‐rooted human teeth with single canals were used. Root canal treatment was performed and canals filled with a core‐carrier obturation technique. The teeth were then randomly assigned to three groups (n = 10). In the first group root canal filling only was performed. After orthograde filling, the teeth of the second group were resected apically, perpendicular to the major axis of the root. In the third group after apical resection, a root‐end cavity was prepared using ultrasonic diamond retrotips and the cavities filled with Super‐EBA cement. During a period of 3 h and with a headspace pressure of 0.12 atm, methylene‐blue solution was forced through a tube that was connected to the apical end of each tooth specimen. The coronal end of the tooth was connected to a capillary tube containing an air bubble. Leakage was evaluated by observing the distal displacement of the air bubble. The roots were then sectioned along their long axis. Using a stereomicroscope, linear dye infiltration at the dentine–cement interface was determined. Kruskal–Wallis and Mann–Whitney tests were used to compare the three groups.

Results  Linear dye infiltration was significantly greater in root canals filled with the core‐carrier obturators and resected apically (0.9 ± 0.9 mm) when compared with those that had root‐end fillings (0.2 ± 0.4 mm). Air bubble displacement was not observed.

Conclusion  Root‐end filling improves the sealing of roots with core‐carrier obturation following root‐end resection.
An in vitro comparison of the bleaching efficacy of 35% carbamide peroxide with established intracoronal bleaching agents
Authors: Lim M. Y. , Lum S. O. Y. , Poh R. S. C. , Lee G. P. , Lim K.‐C.
Published: December 2004

Aim  To evaluate the bleaching efficacy of 35% carbamide peroxide, 35% hydrogen peroxide and sodium perborate for intracoronal bleaching of root filled discoloured teeth.

Methodology  Extracted premolars were artificially stained using whole blood then root canal treatment was performed. After obturation, a 2 mm intermediate base was placed 1 mm below the buccal amelo‐cemental junction. Intracoronal bleaching was performed in 11 teeth per group, using either 35% carbamide peroxide gel (group CP), 35% hydrogen peroxide gel (group HP) or sodium perborate mixed with distilled water (group SP). The bleaching agents were replaced after 7 days. The shade of the teeth was evaluated at day 0, 7 and 14. The results were analysed using Kruskal–Wallis one‐way analysis of variance and Mann–Whitney U‐test.

Results  At the end of 7 days, both groups CP and HP lightened by 8 ± 3 Vita tab positions, respectively, whereas group SP lightened by 5 ± 3 tab positions (P < 0.05). At the end of the second bleaching period at day 14, group CP and HP lightened by a further 2 ± 2 and 2 ± 3 tab positions, respectively, whereas group SP lightened by a further 3 ± 4 tab positions. There were no statistical differences between groups at day 14.

Conclusions  Thirty‐five per cent carbamide peroxide and 35% hydrogen peroxide were equally effective for intracoronal bleaching, and significantly better than sodium perborate after 7 days. After 14 days, there were no significant differences between the groups. Thirty‐five per cent carbamide peroxide can be recommended as an equally effective alternative to hydrogen peroxide for intracoronal bleaching.
FT‐Raman spectroscopy of calcium hydroxide medicament in root canals
Authors: Kwon T. Y. , Fujishima T. , Imai Y.
Published: December 2004

Aim  To investigate chemical changes in calcium hydroxide introduced into human root canals as a medicament using Fourier transform‐(FT) Raman spectroscopy.

Methodology  Ten necrotic maxillary anterior teeth were selected in 10 patients. The teeth were divided into five treatment groups, according to the survey time. Root canal instrumentation was performed with hand instruments until the master apical file was size 40. Calcium hydroxide paste, in a 1 : 1.25 mixture by weight of powder and distilled water, was introduced directly into the root canal with a lentulo‐spiral filler and then condensed with a finger plugger. The access cavity was sealed with a temporary dressing. After 2 and 4 days, then 2, 4 and 6 weeks, the calcium hydroxide paste was sampled with a K‐file and then analysed using FT‐Raman spectroscopy. The excitation source was an Nd : YAG laser with an excitation wavelength of 1064 nm. All spectra were taken with a laser power of 200 mW, 275–1185 scans, and 4 cm−1 resolution. The conversion of calcium hydroxide to calcium carbonate was calculated on the basis of the spectral data obtained from the mixtures of both compounds.

Results  The calcium hydroxide paste in the apical region showed weak bands at 1088 and 284 cm−1, in addition to bands associated with calcium hydroxide. The weak bands, assigned to calcium carbonate, became stronger with time. Calcium carbonate content increased rapidly in the first 2 days and then tended to increase slowly. Approximately 11% of the calcium hydroxide at the apical portion of the canal was converted to calcium carbonate after 6 weeks. However, little alteration of the paste was noticed in the samples from the middle portion of the canal.

Conclusions  Calcium hydroxide medicament in root canals became transformed into calcium carbonate in the apical region within 2 days. Although the transformation continued with time, approximately 90% of the calcium hydroxide remained unchanged after 6 weeks.
Extraradicular diffusion of hydrogen peroxide and pH changes associated with intracoronal bleaching of discoloured teeth using different bleaching agents
Authors: Lee G. P. , Lee M. Y. , Lum S. O. Y. , Poh R. S. C. , Lim K.‐C.
Published: December 2004

Aim  To evaluate the extraradicular pH and hydrogen peroxide (HP) diffusion when either 35% carbamide peroxide (CP), 35% HP or sodium perborate (SP) is used for intracoronal bleaching of artificially discoloured teeth.

Methodology  Single rooted extracted human premolars were stained with whole blood cells. After shaping and cleaning, they were root filled and a base cement placed 1 mm below the buccal cementoenamel junction (CEJ). Four cemental defects were prepared just below the CEJ on each root surface. The teeth were randomly divided into four groups of 11 specimens, and intracoronally bleached using CP, HP, SP or distilled water (CL). Each tooth was suspended in a vial of distilled water and bleached for 7 days. The pH of the extraradicular distilled water was tested at 0, 1, 2 and 7 days and the HP that diffused through the root quantified using the Ferrous Oxidation–Xylenol Orange 2 Assay. The results were analysed using the one‐way anova and Scheffe tests.

Results  Carbamide peroxide produced the greatest increase and HP the least pH change (P < 0.05 except day 1), SP was intermediate. From day 1 onwards, radicular diffusion of HP was greatest with HP and least with CP (P < 0.01), again SP was intermediate. There was no significant difference between CP and SP.

Conclusions  Carbamide peroxide had very low levels of extraradicular diffusion of HP, in the presence of cemental defects. It could be an alternative to the other intracoronal bleaching agents.
The effect of enalapril and verapamil on the left ventricular hypertrophy and the left ventricular cardiomyocyte numerical density in rats submitted to nitric oxide inhibition
Authors: Pereira Leila Maria Meirelles , Mandarim‐de‐Lacerda Carlos Alberto
Published: December 2004

Forty male Wistar rats were separated into four groups of ten rats each (control and other three groups that have received nitric oxide (NO) synthesis inhibitor L‐NAME) but the last two groups have concomitantly received antihypertensive drugs (Enalapril and Verapamil). After 40 days of experimentation, the heart and the ventricles were measured. The optical disector was used for the calculation of numerical density of the cardiomyocytes (Nv[c]). The left ventricular myocytes number (N[c]) was calculated as the product of Nv[c] and the left ventricular myocardium volume (LVMV) that was determined by using the Scherle's method. In the L‐NAME group the blood pressure (BP) had a significant weekly increment. In the enalapril and the verapamil groups, BP increased in the first two weeks, but decreased in the following weeks. The LVMV increased in the L‐NAME rats and decreased in the enalapril and verapamil animals. The Nv[c] and N[c] decreased in the L‐NAME rats but the verapamil and enalapril treatments maintained the Nv[c] close to the control group. In conclusion, the left ventricular hypertrophy and the significant decrease of the left ventricular cardiomyocyte number caused by the NO synthesis inhibition are efficiently prevented with the use of enalapril and verapamil.
Hepatitis B virus and hepatocellular carcinoma
Authors: Arbuthnot Patrick , Kew Michael
Published: December 2004

Chronic hepatitis B virus (HBV) infection is a major global cause of hepatocellular carcinoma (HCC). Individuals who are chronic carriers have a greater than 100‐fold increased relative risk of developing the tumour. Several mechanisms of HBV‐induced HCC have been proposed. Integration of HBV DNA into the genome of hepatocytes occurs commonly, although integration at cellular sites that are important for regulation of hepatocyte proliferation appears to be a rare event. Functions of the HBx protein are also potentially oncogenic. These include transcriptional activation of cellular growth regulatory genes, modulation of apoptosis and inhibition of nucleotide excision repair of damaged cellular DNA. The effects of HBx are mediated by interaction with cellular proteins and activation of cell signalling pathways. Variations in HBV genome sequences may be important in hepatocarcinogenesis, although their significance has not yet been completely elucidated. Necroinflammatory hepatic disease, which often accompanies chronic HBV infection, may contribute indirectly to hepatocyte transformation in a number of ways, including by facilitating HBV DNA integration, predisposing to the acquisition of cellular mutations and generating mutagenic oxygen reactive species. Although HCC is a malignancy with a poor prognosis, the availability of an effective vaccine against HBV infection, and its inclusion in the Expanded Programme of Immunization of many countries, augurs well for the eventual elimination of HBV‐associated HCC.