Positive correlation between p27Kip1 expression and progression of human esophageal squamous cell carcinoma.

Abstract

p27Kip1, one of the cyclin-dependent kinase (CDK) inhibitors (CDKIs), blocks progression from G1 to S phase by binding cyclin D1-CDK4 and/or cyclin E-CDK2 and inhibiting their activities. Reflecting the function of p27 as a CDKI in vitro, a reduced expression of protein p27 has recently been reported to be associated with tumor aggressiveness in some types of human cancers. In the present study, we examined the relationships between immunohistochemically detected expression of p27, cyclin D1, cyclin E proteins and clinicopathological findings in 77 patients with esophageal squamous cell carcinoma (SCC). Using specific monoclonal antibodies to p27, cyclin DI and cyclin E proteins, positive immunostaining in the nuclei was observed in 32.5% (25/77), 27.3% (21177) and 29.6% (21/71) of patients, respectively. There were no statistically significant relationships among the expressions of these 3 proteins. Using the Kaplan-Meier's method, p27 and cyclin D1 expressions were found to be independently associated with poor prognosis. When all parameters were combined into a multivariate regression analysis using the Cox model, the expressions of p27 and cyclin D1 retained a predictive value for survival. In contrast to former reports supporting a tumor-suppressive function of p27, our results suggest that altered expression of p27 and cyclin D1 may be associated with the progression of human esophageal SCC, in which cyclin E may well not play any central role.