PROLIFERATION AND APOPTOSIS IN PROLIFERATIVE LESIONS OF THE COLON ANDRECTUM

Classically, neoplasia has been considered to be primarily a disturban ce in the regulation of proliferation, but it is now clear that progra mmed cell death is dysregulated as well as proliferation. The genes th at are implicated in the regulation of these processes, such as p53, c -myc and bcl-2, are often also altered in neoplasms. We have studied p roliferation and programmed cell death in hyperplastic polyps, adenoma s, carcinomas in adenomas and adenocarcinomas of the colorectum, using the MIB-1 antibody which recognizes the Ki-67 proliferation related a ntigen, and an in situ nick-end labelling procedure for histochemical labelling of proliferating and apoptotic cells. In addition, immunohis tochemistry was used to study the expression of the p53, c-myc and bcl -2 proteins. The material studied consisted of 12 samples of normal mu cosa, 8 hyperplastic polyps, 39 adenomas with different degrees of dys plasia and including 3 that carried a carcinoma, and 10 adenocarcinoma s, all formalin fixed and paraffin embedded. The Ki-67 index indicated that proliferation increased progressively in hyperplasia, through di fferent degrees of dysplasia in adenoma, to reach the highest level (K i-67 index of 50%) in adenocarcinoma. Apoptosis also increased in hype rplastic polyps and in adenomas, but decreased significantly in adenoc arcinomas. p53 Labelling was seen in 77% of the carcinomas but in only 3% of the adenomas. Expression of c-myc increased in adenomas and car cinomas. Furthermore, a shift from predominantly nuclear to predominan tly cytoplasmic expression was seen in progressive neoplasms. Expressi on of bcl-2 was increased in an occasional hyperplastic polyp, but was increased markedly in almost all adenomas. Strikingly, in the adenoma s with a carcinoma, the carcinoma showed weaker bcl-2 expression than the adenoma. In 20% of the carcinomas some bcl-2 staining was seen but this was less extensive than in the adenomas. Our findings indicate t hat in the progression from adenoma to carcinoma both increased prolif eration and decreased apoptosis occur. This is paralleled by an increa sed expression of p53 and an increased and predominantly cytoplasmic e xpression of c-myc, but a decreased expression of bcl-2. This decrease d bcl-2 expression does not lead to an increase in apoptotic activity.