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Altered Expression of p27 and Skp2 Proteins in Prostate Cancer of African-American Patients¹

Department of Pathology [M. D., C. C-C.], Memorial Sloan-Kettering Cancer Center, New York, New York, Departments of Pathology [J. M., R. W., M. P.], Urology [S. T., J. F., I. O.], Environmental Medicine [B. L., A. Z-J.], Medicine [R. P-S.], and Dermatology [K. M., D. P., I. O.], Kaplan Comprehensive Cancer Center [S. T., A. Z-J., R. P-S., M. P., I. O.], New York University School of Medicine, New York, New York

Purpose: The purpose is to investigate the clinical relevance of altered patterns of p27 and Skp2 expression in African-American patients with localized prostate cancer. The abundance of p27, an inhibitor of cell proliferation, is controlled by Skp2-dependent proteolysis.

Experimental Design: A well-characterized cohort of 162 African-Americans who underwent radical prostatectomy at the Veterans Affairs Medical Center of New York between 1990 and 2000 was studied. We analyzed p27 and Skp2 expression by immunohistochemistry. Altered expression of p27 (defined as <40% tumor cells expressing the protein) and Skp2 (defined as 20% tumor cells expressing the protein) were correlated with clinicopathological parameters and time to prostate-specific antigen (PSA) recurrence.

Results: Altered expression of p27 and Skp2 was observed in 112 of 162 (69.1%) and 93 of 162 (57.4%) cases, respectively. Inverse patterns of Skp2 and p27 protein expression were seen in 87 of 162 (53.7%) cases. A marginally significant association was found between Skp2 overexpression and extracapsular extension (P = 0.065). Moreover, patients with Skp2 overexpression had a 2.77 years decreased median time to PSA recurrence compared with patients with low Skp2 expression; however, the difference was not statistically significant. In multivariate analysis, only tumor grade and stage independently predicted PSA recurrence in this cohort.

Conclusions: Our data suggest a role for Skp2 overexpression in prostate cancer pathogenesis that might not be exclusively related to p27 degradation. More studies are needed to determine the mechanistic role of Skp2 in prostate cancer.

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