ABSTRACT
The multistep carcinogenic process of colorectal cancer involves a series of events as oncogenes, inactivation of suppressor genes and abnormalities in cell cycle regulating proteins. This study concerns altered expression and prognostic role of cyclin Dl and p53 in colorectal cancer patients. We evaluate nuclear accumulation of cyclin Dl and p53 immunohistochemically in archival tissue specimens from 41 primary colorectal adenocarcinomas. They had undergone surgery with a median follow up of 23 months [range 1-85 months]. Survival time was analyzed using Kaplan-Meier survival estimates and Cox proportional hazards model for nuclear accumulation of cyclin Dl and p53 with adjustments for other confounding demographic and clinical variables. The expression of cyclin Dl was identified in 41.5% while p53 was expressed in 58.5% of our cases. Cyclin Dl was statistically associated with p53, Dukes stage, nodal state, histologic grade and vascular invasion, but not with age, gender, location, size, gross picture, tumor type, bilharziasis or stromal reaction. p53 was significantly related to male gender and to mucinous and signet ring tumor types but not to either age, location, size gross picture, Dukes stage, nodal state, histologic grade, bilharziasis, stromal reaction or vascular invasion. Using Kaplan-Meier survival curve, cyclin Dl, p53, size, Dukes stage, nodal state and tumor type were significantly correlated with poor survival. By Cox multivariate regression analysis, p53 [relative risk 3.33, 95%-confidence interval 1.39-7.95; p=0.006], nodal state [relative risk 3.17, 95% confidence interval 1.31-7.68; p=0.01] and Dukes stage [relative risk 1.83, 95% confidence interval 1.06-3.15; p=0.027] were independent prognostic indicators in our colorectal adenocarcinoma cases. Our data suggest that cyclin D1/p53 pathway represent a frequent target of the multistep evolution of colorectal carcinoma. Nuclear p53 accumulation combined with nodal state and Dukes stage can predict the clinical behavior of a tumor and high risk colorectal cancer patients. Hence p53 might help to define, a subset of biologically unfavorable neoplasms and improve the prognostic accuracy for colorectal cancer