Summary: Adenoma-carcinoma sequence was postulated for most colorectal carcinomas. Deregulation of apoptosis and cellular proliferation is involved in the pathogenesis of neoplasia. The apoptotic genes that have been characterized in colon cancer are bcl-2, bax, and p53. Studying the expression of these genes and of the proliferating cell marker (Ki-67) in adenoma carcinoma sequence well be of great value in predicting the clinical behavior of benign tumors. We studied formalin fixed, paraffin embedded tissue from 60 cases of adenomas and 100 cases of carcinomas from patients who underwent surgery for removal of colorectal adenoma and/or carcinoma in the period from 1985 to1997 in the VAPHS (Veterans Administration of Pittsburgh Healthcare center). These cases included 28 adenomas with definite evidence of progression to carcinoma. We determined proliferation and apoptosis in normal colonic mucosa, adenomas and carcinomas and related them to the expression of cell cycle and apoptosis associated proteins; Ki-67, bcl-2, bax, and p53 using streptavidin biotin, in situ hybridization, and computerized image analysis techniques. Bcl-2 expression was at its highest level in adenomas, followed by carcinoma which displayed higher level than adjacent normal mucosa in the same specimen. There was progressive increase in bax, p53, Ki-67 and ApopTag labeling indices along normal-adenoma-carcinoma sequence. We found that bax LI was significantly higher in large adenomas and that p53 LI and Ki-67 LI were significantly lower in tubular adenomas
In Conclusion: down regulations of bcl-2 is associated with malignant transformation of colorectal adenoma. P53 mutation and over expression occur early in the transition from adenoma to carcinoma and this leads to down regulation of bcl-2 and induction of bax. Proliferation and apoptosis both increased during progression from adenoma to carcinoma