Prognostic significance of p16 and CDK4 proteins in localized prostate carcinoma

BACKGROUND. In prostate carcinoma, a very low frequency of point mutations of the tumor suppressor gene CDKN2/MTS1 (p16(INK4)) been reported, but dele tions of 9p21 and inactivation by promoter methylation are observed more fr equently. In the current study the authors evaluated the expression of p16 and CDK4 proteins and their prognostic significance in patients with clinic ally localized prostate carcinoma. METHODS. The levels of p16 and CDK4 proteins were quantitated by immunofluo rescence now cytometry, using paraffin embedded material, in 104 adenocarci nomas of the prostate after radical prostatectomy. These levels then were c ompared with 25 cases of benign prostate hyperplasia (BPH). RESULTS. In prostatic carcinoma specimens, p16 protein was elevated signifi cantly compared with BPH, with a median fluorescence index (FI) of 15.4 Ver sus 10.7, respectively (P = 0.010). This was not the case for CDK4 protein, although p16 protein expression correlated significantly with CDK4 protein expression in BPH (Spearman rank correlation [R-S] = 0.63) and carcinoma ( R-S = 0.78). In univariate survival analysis of the first 5 years, high lev els of p16 protein expression (FI > 11.7) (P = 0.005), tumor greatest dimen sion, World Health Organization (WHO) histologic grade; capsular penetratio n, seminal vesicle invasion, positive surgical margins, lymph node involvem ent, and preoperative serum prostate specific antigen > 20 ng/mL all were s ignificant predictors of biochemical failure. In multivariate survival anal ysis, high p16 protein expression (P = 0.015), age, WHO histologic grade, c apsular penetration, and seminal vesicle involvement remained as independen t predictors of biochemical failure. CONCLUSIONS. These data suggest that increased expression of p16 protein, b ut not CDK4 protein, may be involved in the development of prostate carcino ma and may represent an independent predictor of biochemical failure after radical prostatectomy. (C) 2000 American Cancer Society.