Immunohistochemical study, in situ hybridization and computarized image analysis of colorectal epithelial progression from adenoma to carcinoma

Abstract EN

Adenoma-carcinoma sequence was postulated for most colorectal carcinomas.

Deregulation of apoptosis and cell 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 will be of great value in predicting the clinical behavior of benign tumors.

We studied formalin fixed, paraffin embedded tissues 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 to 1997 in the VAPHS (Veterans Administration of Pittsburgh Healthcare System) and UPMC (University of Pittsburgh Medical Centre).

These cases included 28 adenomas with definite evidence of progression to carcinoma.

We determined proliferation and apoptosis in normal colonic mucosa, adenomas & carcinomas and related them to the expression of cell cycle & apoptosis associated proteins; Ki-67, bcl-2, bax and p53 using streptavidin biotin, in situ hybridization and computarized image analysis techniques.

Bcl-2 expression was at its highest level in adenomas, followed by carcinomas 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 & Ki-67 LI were significantly lower in tubular adenomas.