Immunohistochemical detection of p53 protein as a prognostic indicator in prostate cancer

Abstract

Mutation of the p53 gene is the most common genetic alteration in human cancers. The mutant p53 protein is more stable than the wild type and can be detected by immunohistology. The objective of the current study was to evaluate the immunohistological detection of p53 protein in prostate cancer and its utility as a prognostic indicator. We used a monoclonal anti-p53 antibody and immunostained primary prostate adenocarcinomas (stages Al to Dl) from 109 patients with a mean follow-up of 3.8 years (range, 1.3 to 9.3 years). Immunoreactivity for p53 was seen in 23 cancers (21%). There were 12 instances of progression (14%) among the p53-negative cancers versus seven (30%) among the p53-positive group. Survival analysis using three univariate statistical tests showed that p53 reactivity ( P < .03), Gleason score ( P < .01), and stage ( P < .05) had significant effects on time to progression of prostate cancer. Multivariate analyses showed that Gleason score was significant with all three tests; p53 reactivity was significant with the Wilcoxon test but only approached significance by the log rank and Cox tests. When the analyses included only patients with Gleason scores 2 to 7 (N = 94), univariate analyses showed that p53 reactivity was strongly related to progression of prostate cancer ( P < .007). Stage also was significant ( P < 0.04), but Gleason score was not. Multivariate analyses showed only p53 reactivity to be significant ( P < .007). In conclusion, mutation of the p53 gene may be involved in prostate cancer carcinogenesis. p53 reactivity marks an aggressive subset of prostate cancer and appears to be an independent prognostic indicator that is particularly valuable among the low to intermediate grade cancers.