The significance of tumor markers for proliferation and apoptosis in predicting survival in colorectal cancer

PURPOSE: Clinicopathologic staging is even today the best prognostic factor in both colon and rectal cancers. There is still considerable variation in surviva l within the stages. To find other prognostic indicators we investigated six bio logic markers associated with apoptosis and cell proliferation. METHODS: Formali n-fixed, paraffin-embedded tissue samples of 363 patients with primary colon o r rectal cancer of Dukes Stages A to D were chosen for immunohistochemical stain ing of five tumor markers: bcl-2, p53, Ki-67, cyclin D1, and carcinoembryonic antigen. Also, the number of apoptotic cells was studied by the terminal deoxynu cleotidyl transferase-mediated d-UTP nick end labeling method in 347 cases. Th e study was done on specially prepared tissue arrays. RESULTS: In rectal cancer, patients with a Ki-67 labeling index of 5 percent or higher had a better progn osis than those with a lower index. Also, positive cytoplasmic p53 expression pr edicted a favorable outcome in rectal cancer. In colon cancer, positive nuclear staining of cyclinD1 reflected better survival. Weak and moderate staining of ca rcinoembryonic antigen correlated with better prognosis than strong staining, bu t negative staining predicted poor outcome. High apoptotic index of 100 or highe r correlated with poor prognosis in colon cancer. However, in rectal cancer, the trend was the opposite. Bcl-2 staining tended to be more intense in samples of patients living 5 years or longer compared with those with worse prognosis. CON CLUSIONS: Colon cancer and rectal cancer seem to have different biologic behavio r, at least with respect to apoptosis, cytoplasmic p53 expression, and perhaps K i-67 and carcinoembryonic antigen. Further studies are needed to clarify the si gnificance of these factors.