Expression of p53 and bcl-2 in clinically localized prostate cancer beforeand after neo-adjuvant hormonal therapy

The prognostic significance of p53 and bcl-2 expression in prostate carcino ma is currently under investigation. The aim of the present study was to an alyze their expression in diagnostic biopsies and in prostatectomies perfor med after neoadjuvant hormonal therapy to investigate their role in hormone resistance. One hundred and six patients with advanced prostate carcinoma were treated for 3 months with LHRH analogues before radical surgery. The e xpression of p53 and bcl-2 was analyzed by immunohistochemistry in all case s of prostatectomy and in available biopsies obtained before treatment, and was correlated with clinicopathologic parameters and follow-up. A signific ant increase in p53 expression was found following hormonal therapy, wherea s no changes were observed in the expression of bcl-2. The increase in p53 did not correlate with the presence of therapy-induced morphological change s in prostate cancers, but it did correlate significantly with histologic g rade and pathologic stage, biochemical progression of the disease, and shor t overall survival. At multivariate analysis, only grade and stage proved t o be independent predictors of shorter survival. There were no correlations between bcl-2 and clinicopathologic variables whether in biopsies or in pr ostatectomies. The unfavorable clinical course associated with p53-positive carcinomas suggests that neo-adjuvant hormonal therapy may cause the selec tion of minor p53 mutated clones, rather than the induction of wild-type p5 3. In any case, the enhanced expression of p53 could label hormone-resistan t cancers for further adjuvant therapy.