Overexpression of p53 in prostate carcinoma is associated with improved overall survival but not predictive of response to radiotherapy

p53 gene mutations are among the most common specific genetic alterations i n human cancer. Inactivation of p53 and subsequent protein accumulation has been implicated in a variety of human malignancies and associated with pro state cancer progression. In this study, we assessed p53 protein overexpres sion and gene mutations in prostate carcinoma and investigated associations between p53 alterations and clinicopathological parameters, survival, and response to radiotherapy. We evaluated 58 archival formalin-fixed, paraffin -embedded prostate carcinomas to detect abnormal p53 nuclear protein accumu lation using immunohistochemistry. p53 mutational status of tumor DNA was e valuated using polymerase chain reaction-single-strand conformation polymor phism analysis of exons 5-9 and confirmed by direct DNA sequencing. Univari ate and multivariate statistical analysis was used to determine the associa tion of p53 status with clinical characteristics and response to radiothera py. Overexpression of p53 was detected in 42 (72%) of 58 primary prostate c arcinomas, but was undetectable in 7 samples of benign prostatic hyperplasi as or 5 samples of normal prostate tissue. p53 exon 5-9 mutations were dete cted in 8 (14%) of 58 patient specimens. p53 mutational status, but not ove rexpression, was associated with higher Gleason scores (p=0.0145). Neither p53 overexpression nor mutation was associated with clinical stage, biochem ical disease-free probability, or predictive of response to radiotherapy. p 53 protein accumulation was inversely associated with improved overall surv ival (p=0.0108). Our studies demonstrate that p53 protein accumulation is a frequent alteration in prostate cancer. The disparity between p53 protein overexpression and p53 exon 5-9 mutations suggests the possibility of mutat ions outside this 'hot-spot' region or stabilization of wild-type p53 by al ternative mechanisms. In our patient population, p53 protein overexpression or mutational status was not predictive of outcome in patients treated wit h radiation therapy. Additional studies are needed to further evaluate the association between p53 protein overexpression and improved overall surviva l.