Biological correlates of p27 compartmental expression in prostate cancer

Purpose: As one of the cyclin-dependent kinase inhibitors, p27 has been associated with biological behavior and disease progression in malignancies. Materials and Methods: Tissue microarrays were constructed using 640 radical prostatectomy specimens. Normal prostate tissue, benign prostatic hyperplasia and index tumor were cored in triplicate at 0.6 mm. Slides were stained with an antibody to p27 and digitized. The expression of p27 was quantified. SPSS 11.0 (SPSS, Chicago, Illinois) was used to perform the Spearman correlation test, Kaplan-Meier analysis and Cox proportional hazard regression. Results: We noted p27 expression predominately located in the epithelial nuclei of benign and cancer tissues. In PCa p27 was decreased compared to that in normal tissue, while p27 cytoplasmic expression was increased in PCa. Moderate nuclear p27 and cytoplasmic displacement of p27 were associated with worse disease-free survival compared with high or low p27. The cytoplasmic presence of p27 was an independent indicator for predicting the probability of biochemical recurrence in PCa. Conclusions: We report that p27 expression is consistently high in the normal prostate. Moderate levels of nuclear p27 and/or cytoplasmic entrapment of p27 are associated with increased proliferation and worse biochemical recurrence-free survival. These findings suggest that PCa may enhance its growth and progression by decreasing nuclear p27 via cytoplasmic displacement and other molecular mechanisms.