[Correlation of Skp2 and P27kip1 protein expression and clinicopathological features of prostate cancer]

Abstract

Background & objective: The F-box protein Skp2 is required for the ubiquitin-mediated proteolysis of the cyclin-depended kinase inhibitor p27(kip1). Overexpression of Skp2 has been reported in many cancers, including breast carcinoma, gastric carcinoma, and prostate cancer. The purpose of this study was to investigate the correlation of Skp2 and p27(kip1) expression with the clinicopathological features of prostatic carcinoma, and the correlation between expression of Skp2 and p27(kip1) in prostate cancer.

Methods: Skp2 and p27(kip1) protein expression were evaluated in the tissues of 41 human prostatic carcinomas as well as 20 benign prostatic hyperplasia (BPH) using immunohistochemistry (EnVision method).

Results: The Skp2 labeling frequency in prostatic carcinoma (8.52%+/-2.40%) was significantly higher than that in BPH (0.21%+/-0.15%)(P< 0.001). The Skp2 protein expression in prostatic carcinoma was positively correlated with preoperative serum prostate-specific antigen level (r=0.360,P=0.021), extraprostatic extension (r=0.570,P< 0.001), tumor stage (r=0.531, P< 0.001), and histological grade (r=0.514,P=0.001). The p27(kip1) labeling frequency in prostatic carcinoma(70.71%+/-4.25%) was significantly lower than that in BPH (97.21%+/-2.10%) (P< 0.001). The p27(kip1) protein expression in prostatic carcinoma was inversely correlated with preoperative serum prostate-specific antigen level (r=-0.399,P=0.010), extraprostatic extension (r=-0.329, P=0.036), tumor stage (r=-0.453,P=0.003), and histological grade (r=-0.290,P=0.046). Skp2 expression was inversely correlated with p27(kip1) in prostate cancer (rho=-0.572,P< 0.001).

Conclusion: Expression of Skp2 protein may lead to decrease p27(kip1) level in human prostatic carcinoma, indicating its involvement in the development of human prostatic carcinoma. It may provide new targets for the therapy of prostate cancer.