Immunohistochemical expression of insulin-like growth factor binding protein-3 as a predictive marker for the response to hormonal therapy in patients with prostate cancer
Nagasaki University School of Medicine, Nagasaki, Japan
AIM. Insulin-like growth factor binding protein-3 (IGFBP-3) is associated with tumor cell apoptosis. The aim of this study was to assess the cellular expression of IGFBP-3 and correlate the expression with clinicopathological variables and recurrence-free survival in prostate cancer patients undergoing radical prostatectomy after neoadjuvant hormonal therapy (NHT). METHODS. Formalin-fixed, paraffin-embedded specimens of both prostatic biopsy prior to treatment and prostatectomy after NHT from 42 patients with prostate cancer were stained immunohistochemically with anti-IGFBP-3 antibody. The histological effects of NHT in prostatectomy specimens were evaluated according to the Japanese Urological Association Criteria (Grades 0 to 3). In terms of NHT 24 patients were treated with anti-androgens or LH-RH agonist and 18 patients were treated with combined androgen blockade. The median duration of NHT was 8 months (interquartile range, 6 to 10 months). The median follow up period after prostatectomy was 27 months (interquartile range, 13 to 39 months). RESULTS. In biopsy specimens obtained prior to NHT, the median (interquartile range) percentage of IGFBP-3-positive tumor cells was 17.5% (13.6 to 21.3%). The IGFBP-3 expression was not associated with patient age, pretreatment PSA levels, and histological grade. Concerning histological effects of hormonal therapy, 18 patients (42.9%) were good responders. The pretreatment PSA levels, histological grade, T classification, mode of hormonal therapy, and duration of treatment did not predict the histological effect of hormonal therapy (p=0.23, 0.62, 0.43, 0.67, and 0.53, respectively). However, the IGFBP-3 expression in pretreatment specimens was a significant predictive factor of favorable histological effect (Odds ratio 5.2, 95% CI 1.37 to 19.70, p=0.02). In addition, patients with a high IGFBP-3 expression in prostatectomy specimens had a significantly better prognosis in biochemical recurrence-free survival than those with a lower expression (log rank test, p=0.03). CONCLUSIONS. Our results suggest that IGFBP-3 expression in pretreatment specimens may be a useful predictive factor of histological effect of hormonal therapy, and that IGFBP-3 expression can be a prognostic factor in prostate cancer patients undergoing prostatectomy after NHT.
Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Nice, France; February 7 - 10, 2004; in poster session 893 (Molecular pathology).