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Prognostic significance of p16 and CDK4 proteins in localized prostate carcinoma
Author(s) -
Halvorsen Ole J.,
Høstmark Jens,
Haukaas Svein,
Høisæter Per Å.,
Akslen Lars A.
Publication year - 2000
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/(sici)1097-0142(20000115)88:2<416::aid-cncr24>3.0.co;2-#
Subject(s) - prostate , medicine , hyperplasia , prostatectomy , carcinoma , lymph node , pathology , univariate analysis , cancer research , oncology , cancer , multivariate analysis
BACKGROUND In prostate carcinoma, a very low frequency of point mutations of the tumor suppressor gene CDKN2/MTS1 ( p16 INK4 ) has been reported, but deletions of 9p21 and inactivation by promoter methylation are observed more frequently. In the current study the authors evaluated the expression of p16 and CDK4 proteins and their prognostic significance in patients with clinically localized prostate carcinoma. METHODS The levels of p16 and CDK4 proteins were quantitated by immunofluorescence flow cytometry, using paraffin embedded material, in 104 adenocarcinomas of the prostate after radical prostatectomy. These levels then were compared with 25 cases of benign prostate hyperplasia (BPH). RESULTS In prostatic carcinoma specimens, p16 protein was elevated significantly compared with BPH, with a median fluorescence index (FI) of 15.4 versus 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 levels of p16 protein expression (FI > 11.7) ( P = 0.005), tumor greatest dimension, World Health Organization (WHO) histologic grade, capsular penetration, seminal vesicle invasion, positive surgical margins, lymph node involvement, and preoperative serum prostate specific antigen > 20 ng/mL all were significant predictors of biochemical failure. In multivariate survival analysis, high p16 protein expression ( P = 0.015), age, WHO histologic grade, capsular penetration, and seminal vesicle involvement remained as independent predictors of biochemical failure. CONCLUSIONS These data suggest that increased expression of p16 protein, but not CDK4 protein, may be involved in the development of prostate carcinoma and may represent an independent predictor of biochemical failure after radical prostatectomy. Cancer 2000;88:416–24. © 2000 American Cancer Society.