Prognostic significance of p27/kip1 and apoptosis in patients with colorectal carcinoma.

The protein p27/kipl is a cyclin-dependent kinase inhibitor that regulates cell-cycle progression. In the present study, p27/kipl expression as well as tumor cell proliferation and apoptosis were investigated in 80 colorectal carcinomas, using anti-p27/kipl antibodies, in situ apoptosis detection kits and anti-PCNA antibodies. Immunohistochemical staining indicated that p27/kipl was localized heterogeneously in the nuclei of cancer cells. The frequency of samples positive for p27/kipl was 53.8%. (43/80). There was no significant correlation between p27/kipl status and clinicopathologic factors. Mean apoptotic index (AI) in p27/kip1-positive patients (3.22±1.65) was significantly higher than in p27/kip1-negative patients (2.46±1.44; p=0.033). No correlation was observed between p27/kipl expression and the PCNA labeling index (PCNA-LI) (p=0.47). Overall survival was significantly longer for patients who were p27/kip1-positive (80.7%) compared to those who were negative (49.3%; p=0.0003). Univariate analysis revealed no significant differences between prognosis and AI or PCNA-LI. In multivariate analysis, p27/kipl expression was found to be an independent prognostic marker (p=0.015). In conclusion, the present study shows that p27/kipl is a potentially important prognostic and predictive marker for outcome in colorectal carcinoma. These results might be explained by the role of p27/kip1 in promoting apoptosis.