EVIDENCE FOR RECIPROCITY OF BCL-2 AND P53 EXPRESSION IN HUMAN COLORECTAL ADENOMAS AND CARCINOMAS

Evidence is accumulating for the failure of apoptosis as an important factor in the evolution of colorectal cancer and its poor response to adjuvant therapy. The proto-oncogene bcl-2 suppresses apoptosis. Its e xpression could provide an important survival advantage permitting the development of colorectal cancer. The expression of bcl-2 and p53 was determined by immunohistochemistry in 47 samples of histologically no rmal colonic mucosa, 19 adenomas and 53 adenocarcinomas. Expression of bcl-2 in colonic crypts > 5 cm from the tumours was confined to crypt bases but was more extensive and intense in normal crypts < 5 mm from cancers. A higher proportion of adenomas (63.2%) than carcinomas (36. 5%) expressed bcl-2 (P<0.05). A lower proportion of adenomas (31.6%) t han carcinomas (62.3%) expressed p53 (P < 0.02). A total of 26.3% of a denomas and 22% of carcinomas expressed both bcl-2 and p53. To determi ne whether these samples contained cells which expressed both proteins , a dual staining technique for bcl-2 and p53 was used. Only 1/19 aden omas and 2/53 carcinomas contained cells immunopositive for both bcl-2 and p53. Moreover there was evidence of reciprocity of expression of bcl-2 and p53 in these three double staining neoplasms. We suggest tha t bcl-2 provides a survival advantage in the proliferative compartment of normal crypts and colorectal neoplasms. However, its expression is lost during the evolution from adenoma to carcinoma, whereas p53 expr ession is increased, an event generally coincident with the expression of stabilised p53, which we presume to represent the mutant form.