Correlation between proliferation, apoptosis, and angiogenesis in prostatecarcinoma and their relation to androgen ablation

BACKGROUND. Proliferation, apoptosis, and angiogenesis are essential for ca rcinogenesis. Little is known regarding the relation between proliferation, apoptosis, and angiogenesis in untreated prostate carcinoma as well as alt erations associated with androgen ablation. METHODS. Eighty patients who underwent radical prostatectomy for clinically localized prostate carcinoma were recruited for the study. The study popul ation included 2 groups: 35 patients receiving 3-month neoadjuvant hormonal treatment using a combination of luteinizing hormone-releasing hormone ana logue and the antiandrogen flutamide (NHT group) and 45 patients without pr ior treatment (non-NHT group). The authors measured the Ki-67 labeling inde x (Ki-67 LI) by MIB-1 immunohistochemistry, the apoptotic index (AI) by the terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labeli ng technique, and intratumoral microvessel density (IMVD) by CD31 immunohis tochemistry on serial sections of formalin fixed, paraffin embedded tissues . Correlations among these parameters were examined in both groups. RESULTS. A significant decrease in the Ki-67 LI coupled with a significant increase in AI was found in the NHT group compared with the non-NHT group, whereas IMVDs in both groups were not significantly different. AI was relat ed to IMVD inversely in the non-NHT group (correlation coefficient [r] = -0 .327; P = 0.03); in contrast, AI was related to IMVD positively in the non- NHT group (r = 0.579; P < 0.001). The Ki-67 LI was related to AI significan tly in the non-NHT group but not in the NHT group. There was no correlation between Ki-67 LI and IMVD in either group. CONCLUSIONS. Correlations between proliferation, apoptosis, and angiogenesi s in prostate carcinoma are altered significantly in association with andro gen ablation. The results indicate that spontaneous apoptosis is suppressed by neovascularization, whereas hormone-induced apoptosis is enhanced in hy pervascular tumors. (C) 1999 American Cancer Society.