bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adenosquamous carcinoma of the head and neck: criteria for diagnosis in a study of 12 cases
Authors: Alos L , Castillo M , Nadal A , Caballero M , Mallofre C , Palacin A , Cardesa A 
Published: December 2004

Aims:  Adenosquamous carcinoma (ASC) of the head and neck is an unusual neoplasm in which a general consensus with regard to diagnostic criteria has not yet been reached. In this study we report the clinicopathological results of 12 ASCs, with special attention to their histological and immunohistochemical characteristics in order to define this neoplasm more precisely.Methods and results:  All the patients were male with a peak incidence in the sixth decade of life. The tumours were located most frequently in the larynx and oral cavity, followed by the nasal cavity and pharynx. ASCs had two distinct histological components. The most extensive one was an usual keratinizing squamous cell carcinoma, arising from the surface epithelium, where characteristically severe dysplasia or carcinoma in situ was found in all cases. The second component was an adenocarcinoma, usually displayed in the deepest areas of the tumour. Evidence of origin from salivary or seromucinous glands was not found. Immunohistochemical studies demonstrated in most cases positivity of glandular differentiated areas for carcinoembryonic antigen (CEA) (11/12), CK7 (9/12) and CAM5.2 (7/12), whereas the squamous cell component was unreactive or reacted only focally for these markers. High‐molecular‐weight cytokeratin 34BE12 was positive in both components and CK20 was always negative. All cases showed high expression of Ki67 antigen. Most of them had overexpression of p53 (8/12) and DNA aneuploidy (10/12). Fifty percent of patients with ASC died of disease after a mean period of 23 months (range 12–35 months).Conclusions:  ASC of the head and neck is an aggressive neoplasm that originates in the surface epithelium of the upper respiratory tract. Severe dysplasia or carcinoma in situ is usually found and its recognition helps to make the diagnosis. In addition to mucin stains, positive immunoreactivity for CEA, CK7 and CAM5.2 helps to identify the glandular component.
Prognostic impact of histological grade and vascular invasion compared with tumour cell proliferation in endometrial carcinoma of endometrioid type
Authors: Stefansson I M , Salvesen H B , Immervoll H , Akslen L A 
Published: December 2004

Aims:  The relative impact of different prognostic factors is important for endometrial carcinoma patients. The aim of our study was to examine the combined value of histological grade [International Federation of Gynaecology and Obstetrics (FIGO)] and vascular invasion in comparison with tumour cell proliferation assessed by mitotic count and Ki67. The recently proposed binary architectural grade was also evaluated, in addition to age, depth of myometrial infiltration and FIGO stage in our population‐based series of 237 endometrioid carcinomas.Methods and results:  The tumours were studied for several histological features, including FIGO grade, binary grade, vascular invasion, mitotic count, myometrial invasion and expression of Ki67. FIGO grade was significantly associated with all investigated histological features, including Ki67 expression. Vascular invasion was significantly more frequent in FIGO grade 3 tumours, and was associated with a diffusely infiltrative growth pattern, solid growth, necrosis and deep myometrial invasion. All variables showed a highly significant relationship with patient survival in univariate analysis. In multivariate models, FIGO grade, vascular invasion, and proliferation assessed by Ki67 expression all had independent prognostic influence in this population‐based study. Comparing tumour cell proliferation (Ki67) with vascular invasion as a marker of metastatic spread, the latter had a stronger survival impact.Conclusions:  Vascular invasion and tumour cell proliferation measured by Ki67 both had independent prognostic influence, and should be considered to identify aggressive tumours of the endometrioid subtype.
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, Belgium10–15 October 2004 XXVth International Congress. Brisbane, Australia26–27 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.
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.