LOW P27 EXPRESSION PREDICTS POOR DISEASE-FREE SURVIVAL IN PATIENTS WITH PROSTATE-CANCER

Purpose: p27 is an inhibitor of the cell cycle with potential tumor su ppressor function. Decreased levels of p27 protein expression have bee n correlated with poor prognosis in patients with breast and colorecta l carcinomas. Although as many as a third of patients with clinically localized prostate cancer will have relapse after radical prostatectom y, predicting who will have recurrence remains enigmatic. We examined the ability of p27 protein levels to predict outcome in patients with clinically localized disease who underwent radical prostatectomy. Mate rials and Methods: p27 protein expression was evaluated in 86 patients with clinical stage T1-2 prostate cancer who were treated with radica l prostatectomy. Archived paraffin embedded specimens were sectioned a nd immunostained with p27 antibody, and scored by 2 independent observ ers in a blinded fashion. The absence or presence of p27 protein was t hen correlated with biochemical relapse in univariate and multivariate analyses. Results: In a multivariate analysis that included age, preo perative prostate specific antigen, Gleason score and pathological sta ge p27 was a strong independent predictor of disease-free survival (p = 0.0184, risk ratio 3.04), second only to pathological stage (p = 0.0 001, risk ratio 6.73). Even more strikingly, multivariate analysis dem onstrated that p27 was the strongest predictor of biochemical recurren ce (p = 0.0081, risk ratio 4.99) among factors studied in patients wit h pathological T2a-T3b disease. Conclusions: Absent or low levels of p 27 protein expression appear to be an adverse prognostic factor in pat ients with clinically organ confined disease treated by radical prosta tectomy. This marker appears to be especially useful in those patients in whom surgery is believed to be potentially curative, that is patie nts with pathological T2-T3b disease. Patients with low or absent p27 protein expression may be candidates far novel adjuvant therapies.