Expression of VEGF‐D in epithelial ovarian cancer and its relationship to lymphatic metastasis

Abstract

To investigate the contribution of vascular endothelial growth factor (VEGF)-D to tumor progression, tumor lymphangiogenesis and lymphatic metastasis in epithelial ovarian cancer. The expression profiles of VEGF-D in 18 benign, 14 borderline and 87 malignant epithelial ovarian cancers were examined using immunohistochemical (IHC) staining. Lymphatic vessels were identified using IHC staining on lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), which is a lymph-specific receptor for hyaluronan in identifying lymphatic vessels. The potential correlation among VEGF-D, lymphatic vessel density (LVD) and clinico-pathological factors of the epithelial ovarian cancer was also analyzed. Positive IHC staining of VEGF-D was observed in 17% of benign, 21% of borderline and 80% of malignant epithelial ovarian tumors specimens. In the epithelial ovarian cancer specimens, the LVD was 3.41 ± 2.37 in the VEGF-D negative (17 patients), 5.42 ± 3.49 in the weak (26 patients), 7.22 ± 2.36 in the moderate (27 patients) and 7.35 ± 4.06 in the strong (17 patients) groups, respectively. Additionally, the expression of VEGF-D was positively correlated with LVD (r = 0.415, P < 0.001). The expression level of VEGF-D was significantly higher in lymph node-positive epithelial ovarian cancer than in lymph node-negative patients (P = 0.009, P < 0.05). The expression of VEGF-D was significantly correlated with lymph node metastasis, International Federation of Gynecology and Obstetrics stage and tumor histological differentiation, but not with the patients' age or histology type. VEGF-D may play an important role in the process of lymphatic metastasis of epithelial ovarian cancer.