Correlation between vascular endothelial growth factor-C expression and invasion phenotype in cervical carcinomas

The correlation between vascular endothelial growth factor (VEGF)-C gene expression and in vitro invasive activity and matrix metalloproteinase (MMP)-2 or 9 gene expression and proteolytic activity in 11 cervical carcinoma cell lines, was investigated. Immunohistochemical expression of VEGF-C in 52 cervical carcinoma tissues was also correlated with tumor aggressiveness with respect to clinicopathologic features, tumor vascularity, MMP-2 expression and patient outcome. Expression of VEGF-C mRNA differed remarkably among the cell lines and there was a statistical correlation between VEGF-C gene expression and the number of invaded tumor cells (p = 0.0009) and MMP-2 gene expression and activity (p < 0.05). Anti-VEGF-C antibody inhibited the invasive and proteolytic activity of tumor cells in a concentration-dependent manner. VEGF-C or MMP-2 expression in clinical tissue samples was well correlated with depth of myometrial invasion, endometrial invasion, pelvic lymphnode metastasis and tumor vascularity (p < 0.05) and there was a close relation between VEGF-C and MMP-2 expression (p < 0.0001) in cervical carcinomas. Overall survival rates for 14 patients with strong VEGF-C staining tumors were lower than those for 38 patients with weak VEGF-C staining tumors (p = 0.0132) and VEGF-C tissue status emerged as an independent prognostic parameter (p = 0.0232). These results suggest that VEGF-C expression is closely related to invasion phenotype and affects the patient's survival in cervical carcinomas.