Objectives: To determine the effects of neoadjuvant hormonal therapy (NHT) on insulin-like growth factor binding protein (IGFBP)-3 expression and whether IGFBP-3 expression influences the pathologic effect of NHT and biochemical recurrence after radical prostatectomy in patients with prostate cancer. IGFBP-3 has pro-apoptotic activity, and its expression correlates negatively with prostate cancer cell growth. Castration induces IGFBP-3 expression and apoptosis in the rat prostate.
Methods: We used tissue specimens from 42 patients who underwent NHT and radical prostatectomy. The pre-NHT and post-NHT specimens were examined for expression of IGFBP-3 using an immunohistochemical technique and for apoptosis using the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling method. The histopathologic effect was evaluated by the standardized rules for estimating the response of prostate cancer to NHT, determined by the percentage of remaining viable cancer cells, as advocated by the General Rule for Clinical and Pathological Study on Prostate Cancer published by the Japanese Urological Association.
Results: NHT resulted in a statistically significant increase in IGFBP-3 expression compared with baseline (P = 0.01). Such an increase in expression correlated significantly with the induction of apoptotic cells (r = 0.40 and P = 0.01). The post-NHT/pre-NHT IGFBP-3 ratio was significantly greater in the NHT-effective group than in the NHT-noneffective group (P = 0.02). Patients with high IGFBP-3 expression in the post-NHT specimens had a good prognosis (P = 0.03, log-rank test).
Conclusions: Induction of IGFBP-3 by NHT was associated with apoptosis and a histopathologic effect. IGFBP-3 expression in post-NHT specimens is a potentially useful predictor of biochemical recurrence in patients with prostate cancer.