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

ABSTRACT

The protein p27/kip1 is a cyclin-dependent kinase inhibitor that regulates cell-cycle progression. In the present study, p27/kip1 expression as well as tumor cell proliferation and apoptosis were investigated in 80 colorectal carcinomas, using anti-p27/kip1 antibodies, in situ apoptosis detection kits and anti-PCNA antibodies. Immunohistochemical staining indicated that p27/kip1 was localized heterogeneously in the nuclei of cancer cells. The frequency of samples positive for p27/kip1 was 53.8% (43/80). There was no significant correlation between p27/kip1 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/kip1 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/kip1 expression was found to be an independent prognostic marker (p=0.015). In conclusion, the present study shows that p27/kip1 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.