Evidence for post-transcriptional down-regulation of the apoptosis-relatedgene bcl-2 in human colorectal cancer

This retrospective study was undertaken to investigate the expression of bc l-2 protein and messenger RNA in colorectal cancer (CRC). Immunohistochemic al analysis using a monoclonal mouse antibody to the bcl-2 protein and in s itu hybridization using a digoxigenin-labelled bcl-2 cRNA probe were carrie d out on formalin-fixed and paraffin-embedded specimens from 53 colorectal adenocarcinomas, 27 liver secondaries, and 60 adenomas with various degrees of dysplasia, Normal human tonsil sections were used as positive controls. Expression of bcl-2 protein and of messenger RNA was evaluated semiquantit atively. The expression of bcl-2 protein was gradually and significantly lo st during the progression from moderately dysplastic adenoma to primary CRC (moderate/severe dysplasia: Mann-Whitney U-test, p = 0.0001; severe dyspla sia/ primary CRC: p = 0.027), whereas the cellular expression of bcl-2 mRNA was gradually increased during the dysplasia/adenoma-carcinoma neoplastic sequence. These observations suggest that in a proportion of colorectal can cer cases, the bcl-2 proto-oncogene expression may be downregulated at a po st-transcriptional level. Copyright (C) 2000 John Wiley & Sons, Ltd.