Increased hypoxia correlates with increased expression of the angiogenesismarker vascular endothelial growth factor in human prostate cancer

Objectives. To test the hypothesis that increasing levels of hypoxia are as sociated with increased expression of vascular endothelial growth factor (V EGF) in prostate cancer by correlating the level of median tissue oxygenati on in human prostate tumors with the immunohistochemically determined level of VEGF expression. Methods. Custom-made Eppendorf oxygen microelectrodes were used to quantita te the pO(2) levels in prostate tumors of 13 men undergoing radical prostat ectomy. All pO(2) measurements were performed under fluorine-based general anesthesia. Paraffin-embedded tumor tissue from these men was analyzed to m easure the level of VEGF expression by immunohistochemical staining. The si gnificance of the associations between the pO(2) levels and VEGF staining w ere determined by the Pearson correlations. Results. The range of the median pO(2) levels (based on between 97 and 129 individual measurements) among 13 prostate tumors was 0.5 to 44.9 mm Hg. Th e blinded comparison of pO(2) levels and VEGF staining intensity demonstrat ed a significant correlation between increasing hypoxia and the percentage of cells staining positive for VEGF (r = -0.721, P = 0.005). This correlati on was also significant when pO(2) levels were compared with the overall im munoreactive score, which takes into account staining intensity (r = -0.642 , P = 0.018). Conclusions. To our knowledge, this is the first study demonstrating a sign ificant association between increasing levels of hypoxia and increased expr ession of the angiogenesis marker VEGF in human prostate carcinoma. The res ults of our study further support the exploration of antiangiogenesis strat egies for the treatment of human prostate cancer. UROLOGY 57: 821-825, 2001 . (C) 2001, Elsevier Science Inc.