Increased Expressions of Vascular Endothelial Growth Factor (VEGF), VEGF-C and VEGF Receptor-3 in Prostate Cancer Tissue Are Associated with Tumor Progression

Aim: To investigate the differences in microvessel densities (MVD) and the expressions of vascular endothelial growth factor (VEGF), VEGF-C and VEGF receptor-3 (VEGFR-3) between prostate cancer (PCa) tissues and adjacent benign tissues, and to explore the correlations among MVD, Jewett-Whitmore staging, Gleason scores and expressions of VEGF, VEGF-C and VEGFR-3 in the progression of PCa.

Methods: An immunohistochemical approach was adopted to detect the expressions of CD34, VEGF, VEGF-C and VEGFR-3 in both cancer areas and peripheral benign areas of 71 primary prostatic adenocarcinoma specimens. A statistic analysis was then performed according to the experimental and clinic data.

Results: Significantly upregulated expressions of VEGF, VEGF-C and VEGFR-3 were all found in malignant epithelium/cancer cells compared with adjacent benign epithelium (P<0.01). Patients in stage D had a significantly higher score than patients in stage A, B or C when comparing the expression of VEGF-C or VEGFR-3 in the tumor area (P<0.01). In addition, significant correlations were observed between Jewett-Whitmore staging and VEGF-C (r(s)=0.738, P<0.01), clinical staging and VEGFR-3 (r(s)=0.410, P<0.01), VEGF-C and Gleason scores (r(s)=0.401, P<0.01), VEGFR-3 and Gleason scores (r(s)=0.581, P<0.001) and MVD and VEGF (r(s)=0.492, P<0.001).

Conclusion: Increased expressions of VEGF and VEGF-C were closely associated with progression of PCa. The main contribution of increased VEGF expression for PCa progression was to upregulate MVD, which maintained the growth advantage of tumor tissue. However, the chief role of increased expressions of VEGF-C and VEGFR-3 was to enhance lymphangiogenesis and provide a main pathway for cancer cells to disseminate.