Vascular Endothelial Growth Factor D and Intratumoral Lymphatics as Independent Prognostic Factors in Epithelial Ovarian Carcinoma

Abstract

Lymph node metastasis is an important prognostic indicator for disease progression and is crucial for therapeutic strategies of epithelial ovarian carcinoma. Vascular endothelial growth factor (VEGF)-D has been confirmed to have potent lymphangiogenic function in experimental models, but the role in the progression of human ovarian carcinoma remains presently controversial. The purpose of this study was to investigate the prognostic significance of VEGF-D and the presence of intratumoral lymphatics in patients with epithelial ovarian carcinoma. The VEGF-D expression was evaluated by immunohistochemistry in 78 specimens of epithelial ovarian carcinoma and tumoral lymphatic vessels were measured by D2-40. The expression of VEGF-D protein was detected in the cytoplasm of the tumor cells and in stroma occasionally. The high expression of VEGF-D was closely associated with the FIGO stage, intratumoral lymphatic vessels, tumoral lymphatic invasion, and lymph node metastasis as well as a shorter overall survival. Univariate and multivariate analysis indicated that VEGF-D, intratumoral lymphatics, and lymphatic invasion were independent prognostic factors for overall survival and disease-free survival in patients with epithelial ovarian carcinoma. We conclude that VEGF-D plays an essential role in tumoral lymphangiogenesis and lymphatic spread, VEGF-D expression, and the intratumoral lymphatics may be clinically useful indicators for prognostic evaluation in patients with epithelial ovarian carcinoma.