Apoptosis, mitosis, p53, Bcl(2), Ki-67 and clinical outcome in prostate carcinoma treated by androgen ablation

A prospective study on 16 patients with advanced (stage III and IV) prostat e cancer was carried out. TNM stage, general clinical status, serum PSA lev el, the histological type and Gleason's grade of the tumor were registered. Total androgen blockade or single-drug therapy (flutamide) was performed. On average, 4.81 months after the start of therapy rebiopsy, serum PSA dete rmination and general clinical examination were performed. Histologic exami nation before and after treatment of HE-stained slides, as well as apop-tag reaction to show apoptotic cells, p53, bcl(2), and Ki-67 immunostaining. C linical improvement manifested by regression or lack of progression was obs erved in 10 patients. Increase of the apoptotic index and decrease of the m itotic index was detected in these cases. Serum PSA level decreased in all patients except in 3 fatal cases. The 6 clinically nonresponders who died a fter the second biopsy did not show an increased apoptotic or decreased mit otic index. Ki-67 positivity correlated well with the mitotic activity. Mut ant p53 expression was higher in patients in whom antiandrogen therapy was ineffective. The bcl(2) expression was a characteristic of the tumors of pa tients who later died. These results show that the degree of induction of a poptosis in prostate carcinoma by hormonal therapy varies from case to case . A given prostate cancer patient's response to therapy may be predicted by following apoptotic and mitotic activity, as well as Ki-67 and p53 express ion in repeated biopsies. Copyright (C) 1999 S. Karger AG, Basel.