Includes bibliographical references (leaves 49-55).Beta-catenin is normally complexed with adenomatous polyposis coli (APC) protein and E-cadherin adhesion molecule, and localized on the cell membrane. If APC/beta-catenin is disrupted, beta-catenin transfers into the nucleus, where it functions as a transcriptional activator, causing unregulated cell proliferation. The localisation of beta-catenin in H NPCC adenomas has not been studied but a shift in beta-catenin to the nucleus has been previously demonstrated in a range of col 0 recta I cancers, including those in HNPCC. The aim of the first part of the study was to determine whether there is a beta-catenin shift occurring as an early event in HNPCC tumours. Coded sections of tumours were immunohistochemically stained with antibody against beta-catenin and counterstained in haematoxylin. 14 HNPCC adenomas, 13 HNPCC carcinomas, 10 FAP adenomas, 10 FAP carcinomas, 10 sporadic adenomas and carcinomas and 10 juvenile polyps -three with dysplasia and seven without- were studied. A score was given for loss of membrane staining (0-1), presence of cytoplasmic staining (0-2) or nuclear staining (0- 2) and a total out of five obtained. An shift in beta-catenin was demonstrated at the adenoma phase in HNPCC. HNPCC, tumours were compared with sporadic tumours and a statistically significant similarity in prevalence of beta-catenin shift found in adenomas and carcinomas. The early shift in beta-catenin in HNPCC led to the second part of the study evaluating the "down-stream" effects of this shift in HNPCC tumours. TheHNPCC sections were immunohistochemically stained with E-cadherin, cmyc and cyclin 01. The results showed a positive correlation between Ecadherin loss, increased cyclin 01 and a shift in beta-catenin. No significant change in c-myc or correlation between c-myc and a shift of beta-catenin was found. In conclusion the study indicates that disruption of the APC/beta-catenin pathway plays a similar role in HNPCC tumours to that in sporadic tumours. A notable exeption is the effect on c-myc and further study is needed in this regard
