VEGFR1 and NRP1 Endothelial Expressions Predict Distant Relapse after Radical Prostatectomy in Clinically Localized Prostate Cancer

Prostate cancer can usually be treated at a clinically localized stage by radical prostatectomy. Unfortunately, within 10 years following surgery, 30% of patients experience local or distant relapse. Few data exist on the association of markers of angiogenesis and distant relapse after radical prostatectomy. By immunohistochemistry in tissue microarray, we compared the expression pattern of hypoxia inducible factor 1, alpha subunit (HIF1 alpha) and vascular endothelial growth factor (VEGF) and its receptors in 45 patients with distant relapse and 68 patients without relapse after radical prostatectomy. Expressions of HIF1 alpha and VEGF were assessed in prostate tumor cells and those of VEGFR1, VEGFR2 and neuropilin 1 in tumor and endothelial cells. The five molecules studied were expressed by all tumors, with the exception of neuropilin 1 in endothelial cells for one tumor. Strong endothelial expression of VEGFR1 appeared to be an independent predictor of distant relapse. A moderate to strong endothelial expression of neuropilin 1 was in turn an independent predictor of absence of distant relapse. No significant difference was found for HIF1 alpha, VEGF, VEGFR1, VEGFR2 and neuropilin 1 expression in tumor cells, nor for VEGFR2 in endothelial cells, between the two groups. To our knowledge, this is the first study to evaluate the prognostic value of VEGFR1, VEGFR2 and neuropilin 1 in endothelial cells in prostate cancer after radical prostatectomy. The evaluation by immunohistochemistly of endothelial expression of neuropilin 1 and VEGFR1 could be an additional tool in the assessment of tumor aggressiveness of clinically localized prostate cancer to better identify patients at high risk of distant relapse.