Castration resistant prostate cancer is associated with increased blood vessel stabilization and elevated levels of VEGF and Ang‐2

BACKGROUND Angiogenesis is important for the progression of prostate cancer and may be a target for treatment in castration resistant (CR) disease. This study was performed to investigate blood vessel stabilization and expression of the pro-angiogenic factors vascular endothelial growth factor (VEGF) and Angiopoietin-2 (Ang-2) in CR and hormone naive (HN) prostate cancer. The effect of androgen deprivation therapy (ADT) on these parameters was also studied. METHODS VEGF and Ang-2, as well as pericyte coverage of blood vessels were studied in HN and CR prostate tumors by immunohistochemistry. The effects of ADT on VEGF expression and microvessel density (MVD) were investigated in biopsies at diagnosis, 3 months after starting ADT and at tumor relapse. Plasma was also analyzed for VEGF and Ang-2 with ELISA. RESULTS CR tumors had higher levels of VEGF and Ang-2 as well as increased blood vessel stabilization compared to HN tumors. Three months after initiated ADT an increase of VEGF but not MVD in the tumors was observed. In contrast, plasma levels of VEGF decreased after ADT, and increased again at time of tumor relapse. Ang-2 levels were unaffected. CONCLUSIONS CR prostate cancer is associated with elevated levels of VEGF and Ang-2, indicating that these factors could be used as targets for anti-angiogenic treatment. Still, the observed increase in blood vessel stabilization in CR tumors could influence the outcome of anti-angiogenic treatment. Furthermore, increased VEGF expression after 3 months of ADT justifies the use of VEGF-based anti-angiogenic drugs in combination with ADT for the treatment of advanced prostate cancer. Prostate 72:705–712, 2012. © 2011 Wiley Periodicals, Inc.