Immunohistochemical study of p21WAF1 and p53 proteins in prostatic cancer and their prognostic significance

Mutations of p53 tumor suppressor gene occur in a subset of aggressive prostatic carcinomas and are detectable by immunohistochemistry. However, it is uncertain whether p53 overexpression really reflects p53 gene mutation or loss of p53 function. p21(WAF1) an inhibitor of cyclin-dependent kinases, is activated by wild-type p53 protein, not by mutant type. Therefore, it is possible that combined analysis of p21(WAF1),and p53 proteins aids in determining the functional status of p53 immunostaining. Routinely processed prostatic tissues from 60 patients with prostatic adenocarcinomas were examined by immunohistochemistry for p21(WAF1) and p53 expression. As for tissue distribution, p21(WAF1) protein was expressed mostly in the luminal layers, in contrast, p53 protein was restricted to the basal layers of benign prostatic glands. In prostatic adenocarcinomas, p21(WAF1) protein was more likely to be expressed in well-differentiated areas; in contrast, p53 protein was more likely in poorly differentiated areas in the tamers. The percentage of positive nuclear areas for p21(WAF1),and p53 proteins in prostatic adenocarcinomas, assessed by CAS 200 computerized image analyzer, were 8.6 +/- 10% and 16 +/- 14% (mean +/- SE), respectively. The survival study showed that the p53+/ p21- phenotype showed poorer prognosis than p53+/p21+. Multivariate analysis showed that p21(WAF1) expression, clinical stage, and Gleason score were independent prognosticators. In conclusion, p21(WAF1) immunohistochemistry is a useful method for interpretation of p53 immunohistochemical results. Combined analysis by p21(WAF1) and p53 immunostaining would predict the patient survival more accurately than p53 immunostaining alone. Copyright (C) 1998 by W.B. Saunders Company.