Prostate Cancer; the interface between Pathology and basic Scientific Research

Current research into prostate cancer increasingly demands greater input from pathologists. There is a requirement for improved morphological assessment, classification and grading of neoplasia. The provision of optimally preserved material and establishment of tissue \u27banks\u27 is vital to facilitate molecular biological analysis. Microdissection of archival material can provide a source of relatively pure DNA and mRNA which can \u27be further amplified by PCR/RT-PCR. This enables allelic imbalance, point mutations and other genetic abnormalities to be demonstrated. In-situ hybridization for mRNA is feasible on fixed tissues and allows precise localization of gene expression on complex tissues or for labile gene products. Experimental models including transgenic mice and in-vitro co-culture systems require sophisticated morphological analysis. Experts in morphological analysis are essential members of basic scientific and translational research teams

Characterization of Monoclonal antibodies raised to C-terminal Peptides of pS2: A major Trefoil peptide and motility factor expressed in Adenocarcinomas and regions of Mucosal Injury

Two novel monoclonal antibodies, GE1 and GE2 raised against the C-terminal 31 and 28 amino acids of the estrogen-inducible trefoil peptide pS2, are described. Both antibodies are able to detect pS2 in formalin-fixed, paraffin-embedded tissues. Conditions are presented under which pS2 can be shown in cell lines by immunohistochemistry that has previously been problematic. The antibodies can specifically show the presence of pS2 in cell lysates by Western blotting and immunoprecipitation. In the form of an affinity column, the GE1 monoclonal antibody can be used to purify pS2 from MCF-7 supernatants. The eluted peptide from the GE1 affinity column shows a single band at 6,600 Da (predicted size for pS2) on Western blotting. These antibodies are valuable reagents in the analysis of the role of trefoil peptides in the maintenance of mucosal integrity, and may have applications in the assessment of pS2 expression in chronic gastrointestinal ulceration and adenocarcinomas that secrete pS2, where it may serve as a prognostic marker

Expression of bcl-2 and p53 Oncoproteins in Schistosomiasis-associated transitional and Squamous Cell Carcinoma of Urinary Bladder

Objectives: To analyse the expression of bcl-2 and p53 proteins in schistosomiasis-associated bladder cancer compared to adjacent urothelium showing morphological alteration including hyperplasia, metaplasia and dysplasia. Materials and Methods: Twenty-two formalin-fixed and paraffin-embedded samples of histologically confirmed schistosomiasis-associated bladder tumours were assessed for grade, pathological stage (pT category) and the presence of hyperplasia, metaplasia and dysplasia in adjacent mucosa. There were 11 transitional cell carcinomas (TCCs), 10 squamous cell carcinomas (SCCs) and one diffuse infiltrating (signet-ring cell type) adenocarcinoma. Epithelial hyperplasia was observed in seven cases and metaplasia in 18, most of which were squamous except for a single case of glandular metaplasia. Focal dysplastic areas were observed in eight cases. Sections were stained immunohistochemically for the expression of bcl-2 and p53 proteins. Results: Immunoreactivity for bcl-2 was present in seven of 22 cases (four SCCs and three TCCs) of which three cases (two SCCs and one TCC) were strongly positive, but in contrast to previous studies, there was no increase in the poorly differentiated tumours. bcl-2 was absent in metaplastic and dysplastic epithelium (except in a single case of glandular metaplasia) but it was present at low levels in basal cells of morphologically normal or hyperplastic transitional epithelium in 15 of 22 cases. Nine of 11 TCCs and seven of 10 SCCs showed p53 nuclear immunoreactivity. Heterogenous weak to moderate immunoreactivity for p53 was seen in 13 of 18 cases of metaplasia and in seven of eight cases of dysplasia in the mucosa adjacent to tumours. p53 was absent in normal and hyperplastic urothelium. Co-expression of p53 and bcl-2 was only seen in well differentiated areas of three tumours (two SCCs and one TCC). Conclusion: This study detected the expression of bcl-2 in a subset of bladder cancers (32%), whereas most (72%) of the tumours expressed immunoreactive p53. Additionally, p53 was also detected in metaplastic and dysplastic epithelium. Over-expression of both p53 and bcl-2 in the same tumour was only evident in a minority of schistosomiasis-associated cancers (13%). There was no inverse relationship of p53 and bcl-2 immunoreactivity