Abstract: Adenoma-carcinoma sequence was postulated for most colorectal carcinomas. Deregulation of apoptosis & cell proliferation is involved in the pathogenesis of neoplasia.  The apoptosis genes characterized in colon cancer are bcl-2, bax & p53. b-catenin plays a role in both cell adhesion & intracellular signaling. Translocation of b-catenin from the cell membrane to the cytoplasm or nucleus is an early event in colorectal carcinogenesis. Transducer & activator of transcription STAT-3 signaling directly contributes to oncogenesis by stimulating cell proliferation & preventing apoptosis. There are still controversies about the relationship between STAT-3 and bcl-2-family

We studied 48 adenomas & 52 carcinomas, using immunohistochemical staining & computerized image analysis techniques and a panel of antibodies against bcl-2, bax, p53, b-catenin & STAT-3. We also used in situ hybridyzation to detect apoptotic bodies. These included 14 cases that showed definite morphologic evidence of progression from adenoma to carcinoma

Consistent reduction of bcl-2 & STAT-3 & consistent increase in bax, p53 & Ki-67 were found comparing carcinoma group to adenoma group. On progression from adenoma to carcinoma: we found significant increase in apoptosis, p53 and Ki-67, increase in bax, and significant decrease in bcl-2, STAT-3 and b-catenin. Nuclear localization of b-catenin was consistently higher in carcinomas than adenomas

Aim of the study: This study was designed to define immunohistochemical markers that may characterize the progression from adenomas to carcinomas, which may be used diagnostically as an early detection tool to predict tumor progression

Conclusion: 1- Down-regulation of bcl-2 is associated with malignant transformation of colorectal adenomas.   2- p53 mutation  & over-expression occurs early in the transition from adenoma to carcinoma & this leads to down-regulation of bcl-2 & induction of bax. 3- Nuclear accumulation of b-catenin may be an early events that defines malignant transformation. 4- Activated STAT-3 stimulates cell proliferation & prevents apoptosis through the induction of bcl-2 in adenomas conferring a survival advantage that allows more time for mutation to be propagated by cell division.