Vascular endothelial growth factor C and vascular endothelial growth factor receptor 2 are related closely to the prognosis of patients with ovarian carcinoma

BACKGROUND: The vascular endothelial growth factor (VEGF) family and VEGF receptors (VEGFR) play an essential role in the angiogenesis of both pathologic and nonpathologic conditions. However, the prognostic significance of VEGF and VEGFR expression in ovarian carcinoma is unclear. METHODS: The tissue expression levels of VEGF-A, VEGF-C, VEGFR-2, and VEGFR-3 in 80 specimens of ovarian carcinoma were examined immnohistochemically. The results obtained were analyzed clinicopathologically. RESULTS: VEGF-A, VEGF-C, VEGFR-2, and VEGFR-3 were expressed both in tumor cells and in adjacent endothelial cells of blood and lymph vessels. The tissue expressions of VEGF-C and VEGFR-2 were correlated significantly with tumor extension, including peritoneal metastases outside the pelvic cavity (P = 0.0010 and P = 0.0008, respectively), lymph node metastases (P = 0.0030 and P = 0.0018, respectively), and positive ascitic cytology (P = 0.025 and P = 0.0016, respectively). Conversely, there was no significant correlation between VEGF-A and VEGFR-3 expression and clinicopathologic features of ovarian carcinoma. Logistic regression analysis revealed that the expressions of VEGF-C and VEGFR-2 also were independent risk factors for peritoneal and lymph node metastases. Survival curves determined by the Kaplan-Meier method and in univariate analysis demonstrated that high expression levels of VEGF-C and VEGFR-2 were associated with the 5-year survival rate. In multivariate analysis, high expression levels of VEGF-C and VEGFR-2 emerged as independent indicators for disease-specific survival. CONCLUSIONS: High tissue expression of VEGF-C and VEGFR-2 reflects the aggressiveness of the spread of tumor in ovarian carcinoma. Thus, both have predictive value for identifying high-risk patients who have a poor prognosis.