Abstract: The vast majority of colorectal carcinoma are widely believed to arise from polypoid adenomas. The apoptotic related genes that have been most consistently characterized in colonic cancer are bcl-2, bax, and p53. Studying the expression of these genes in adenoma carcinoma sequence will be of great value in producing the clinical behavior of benign tumors. Loss of contact inhibition and adhesion molecules are indicators of progression to more dysplastic epithelial pre-carcinoma  lesions, as colorectal; adenoma. Translocation of β-catenin from the cell membrane to the cytoplasm/nucleus is believed to be an early event in the development of colorectal neoplasm. We examined 13 cases that showed definite progression from adenoma to carcinoma. In situ hybridization using ApopTag was performed to detect apoptotic bodies. Immunohistochemical staining was performed using bcl-2, bax, p53 and β-catenin monoclonal antibodies, and Ki-67 polyclonal antibody.  Computerized image analysis was done to semi quantitate protein expression in each stain. On progression from adenoma to carcinoma apoptotic bodies were significantly increased (p>0.04), bcl-2 was significantly decreased (p>0.01), bax, p53 and Ki-67 were all significantly increased (p>0.04, 0.002, and 0.000 respectively).  There was a significant decrease in β-catenin stain in the progression from adenoma to carcinoma (p>0.001). but its nuclear position was consistently higher in carcinomas (p>0.000)

Conclusion: Down-regulation of bcl-2 is associated with malignant transformation of colorectal adenoma. P53 mutation and overexpression occur early in the transition from adenoma to carcinoma and this leads to down regulation of bcl-2 and induction of bax. Nuclear accumulation of β-catenin may be an early event that defines malignant transformation