Search

Aims: To establish the prevalence of cyclooxygenase-2 (COX-2) expression in a large series of resected Barrett's adenocarcinoma and associated preneoplastic lesions and to correlate this expression with clinicopathological data and prognosis. Methods: COX-2 expression was assessed by immunohistochemistry in resected surgical specimens of 66 Barrett's adenocarcinomas and 32 cases of Barrett's mucosa (with dysplasia in 17 cases). Results: Epithelial expression of COX-2 protein was increased in Barrett's mucosa compared with normal oesophagus. Epithelial expression of COX-2 was found in 91% of Barrett's specialized mucosa negative for dysplasia, 94% of Barrett's mucosa with dysplasia, and 97% of Barrett's adenocarcinoma. COX-2 expression was significantly higher in the well-differentiated adenocarcinomas when compared with the poorly differentiated tumours. There was no significant correlation between COX-2 expression and the other pathological features of the tumours. Survival analysis showed no significant prognostic value for COX-2. Conclusion: Our results confirm up-regulation of COX-2 in Barrett's oesophagus—metaplastic and dysplastic—and in Barrett's adenocarcinoma. Increased COX-2 expression did not differ during the progression from Barrett's oesophagus negative for dysplasia to Barrett's adenocarcinoma and is related to adenocarcinoma whose histology is well differentiated. This suggests that enhanced expression of COX-2 may occur early during Barrett's-associated neoplastic transformation. [ABSTRACT FROM AUTHOR]

SUMMARY Glomerulonephritis with organized microtubular monoclonal immunoglobulin deposits (GOMMID) and glomerulonephritis related to type I cryoglobulin are well-known but rare complications of B cell derived chronic lymphocytic leukaemia. In these disorders, monoclonal Ig have never been studied at the molecular level. We conducted a pathological and molecular analysis in a patient with chronic lymphocytic leukaemia, glomerulonephritis and a single circulating monoclonal Ig. Unusual IgG1κ kidney deposits were observed. The heavy and light chain variable region sequences of that cryoprecipitating monoclonal Ig were characterized. Light microscopy revealed glomerulonephritis typical of cryoglobulinaemia, with neutrophil and macrophage infiltration, endocapillary hyperplasia and few protein thrombi. Electron microscopic study clearly evidenced numerous subepithelial mixed granular and organized deposits with a unique microtubular organization, reminiscent of the GOMMID. The Ig molecule sequence revealed alterations of charge and hydrophobicity potentially promoting a crystal-like aggregation and the aggregation of microtubules.This description suggests that common mechanisms are involved in various forms of precipitation and/or deposition of complete Ig molecules, with a variable extent of organization and with a possible overlap between pathological patterns of either glomerulonephritis with microtubular deposits or type I cryoglobulinic glomerulonephritis. [ABSTRACT FROM AUTHOR]

MLH1 and MSH2 protein immunohistochemistry is useful for detection of hereditary non-polyposis colorectal cancer in young patients Aims: Hereditary non-polyposis colorectal cancer is related to germline mutations of DNA mismatch repair genes MLH1 and MSH2 , which result in microsatellite instability and loss of protein expression of the corresponding mutated gene in the tumour tissue. Methods and results: MLH1 and MSH2 protein expression was studied by immunohistochemistry in paraffin-embedded surgical samples of 100 colorectal adenocarcinomas occurring before 50 years of age. Absence of tumour cell nuclear staining with positive internal control (normal mucosa, lymphoid follicles) was considered negative. Loss of MLH1 or MSH2 expression was found in 20 cases with microsatellite instability in 15 cases. Twelve of these patients had a family history of colorectal cancer. Compared with MLH1- and MSH2-positive cases, MLH1- or MSH2-deficient colorectal adenocarcinomas were significantly associated on multivariate analysis with a younger age (38 vs. 43 years, P; 0.0224), a larger tumour size (60 ± 6 vs. 46 ± 2 mm, P =0.0291), an expanding margin (85% vs. 51%, P =0.0159), a higher number of tumour-infiltrating lymphocytes assessed by CD3 immunostaining (202 ± 48 vs. 33 ± 4 CD3+ lymphocytes/10 high-power fields, P =0.0039), and a grade 2 Crohn's like lymphoid reaction (70% vs. 9%, P =0.0037). The two groups were not different for tumour site, differentiation, pTNM stage, vascular and perineural invasion, peripheral adenomatous residue, and 5-year survival rates. Conclusions: MLH1- or MSH2-deficient colorectal carcinomas of young patients exhibit pathological and molecular features similar to hereditary non-polyposis colorectal cancer. This suggests that MLH1 and MSH2 immunohistochemistry is valuable for detecting hereditary non-polyposis colorectal cancer in young patients. [ABSTRACT FROM AUTHOR]

A longitudinal study of elastic fibres was conducted in liver biopsies from 21 patients with chronic viral hepatitis. Biopsies were taken at the start of treatment with alpha-interferon, and after 6 months or 1 year of treatment. No elastic fibres could be detected in portal tracts or fibrous septa when inflammation and necrosis were present, whatever the duration of the disease. Once the liver lesions had healed, elastic fibres were synthesized. Fibres were of two types and patterns: at first, they were thin, long and parallel to each other. Later, they were thicker, shorter and tortuous and were closely wrapped around thick bundles of collagen fibres. These findings suggest that the deposition of elastic fibres acts as a marker of healing in chronic active hepatitis and that their remodelling occurs concomitantly with the deposit of large bundles of collagen fibres. [ABSTRACT FROM AUTHOR]

AIMS--To establish the prevalence of c-erbB-2 protein expression in a surgical series of Barrett's adenocarcinomas; and to correlate this expression with clinicopathological data and prognosis. METHODS--Sixty six surgical specimens of Barrett's adenocarcinomas were included in this retrospective study. Blocks of the tumour and of non-dysplastic Barrett's mucosa were stained with a polyclonal antibody specific for the intracytoplasmic domain of the c-erbB-2 protein. RESULTS--Seven of 66 tumours showed membrane staining for the c-erbB-2 protein. The non-dysplastic Barrett's mucosa was negative in all cases. There was no difference between c-erbB-2 positive and negative tumours with regard to mean age, sex ratio, percentage of alcohol misusers, percentage of smokers, tumour differentiation, depth of invasion, lymph node response, and proliferative activity, assessed by the percentage of tumour cells positive with the MIB-1 antibody directed against the Ki-67 antigen. All c-erb B2 positive tumours were of Lauren's intestinal type compared with negative c-erbB-2 tumours. Patients with c-erbB-2 positive tumours had a significantly poorer prognosis than patients with negative tumours. CONCLUSIONS--The prevalence of Barrett's adenocarcinomas expressing c-erbB-2 found in this study (11%) was similar to that observed in published series of gastric adenocarcinomas. c-erbB-2 protein expression could be an important prognostic indicator in Barrett's adenocarcinoma. [ABSTRACT FROM PUBLISHER]

Objective To evaluate the accuracy of endorectal magnetic resonance imaging (MRI) with fast spin-echo sequences in the local staging of clinically localized prostate cancer. Patients and methods Seventy-one patients with a clinical T1 (18 patients) or T2 tumour (53 patients) underwent endorectal MRI 2-12 weeks before radical prostatectomy. Extraprostatic tumour was diagnosed if MRI showed signs of capsular penetration and/or invasion of the seminal vesicle and/or distal urethra or bladder neck. If the pathological examination showed a single positive margin with no periprostatic tissue, the tumour was classified as indeterminate and not as a T3 tumour. Results Of the 25 cases of capsular penetration, MRI correctly identified 10 (sensitivity 42%, specificity 100%). Of the 14 cases with seminal vesicle invasion, MRI correctly identified six (sensitivity 43%, specificity 100%), but showed other signs of extraprostatic tumour spread in seven of the eight unidentified cases. Overall, MRI identified 16 of the 30 patients (53%) with occult extraprostatic spread of tumour; there was only one false-positive result. The sensitivity, specificity and accuracy of MRI were 53, 96 and 74%, respectively. Conclusion Endorectal MRI can reduce the rate of pre-operative understaging from 42% to 22% and it can be used for a given individual because it can detect extraprostatic invasion with 96% specificity, ensuring that very few, if any, patients will be deprived of curative surgery. [ABSTRACT FROM AUTHOR]