Expression of vascular endothelial growth factor receptor-3 (VEGFR-3) in human prostate

BACKGROUND. The growth and dissemination of tumors has been associated with angiogenesis, which is regulated by a group of polypeptide factors including vascular endothelial growth factor-C (VEGF-C). VEGF-C binds its receptor, vascular endothelial growth factor receptor-3 (VEGFR-3) to promote growth of tumor-associated lymphatic vessels. METHODS. In this study, microarray technology was used to build tissue arrays of normal prostate, benign prostate hyperplasia (BPH) and prostate carcinomas (PCa) using tissues from 640 patients. Slides were sectioned and stained with a polyclonal antibody to VEGFR-3 using a standard immunoperoxidase method and digitized. Immunoreactivity was scored using a 0-3+ semiquantitation scoring system for both intensity and percentage. The sum index was obtained by totaling the scores. RESULTS. VEGFR-3 is expressed in normal prostate, BPH, and PCa, but VEGFR-3 expression is up-regulated in PCa. We also found that VEGFR-3 is correlated with pre-operative prostate-specific antigen (Pre-PSA), Gleason score, and lymph node metastasis. The recurrence-free 5-year survival in cases with lower sum index (0-3) was significantly higher than that in cases with higher sum index (4-6) (77.3, 69.6%, respectively, P = 0.037) by Kaplan-Meier actuarial model. CONCLUSIONS. Our data suggest that VEGFR-3 expression is associated with tumor progression and may play an important role in facilitating lymphatic spread of PCa; high-level of VEGFR-3 expression in prostate cancer cells increases the risk of biochemical recurrence in prostate cancer patients treated by radical prostatectomy.