High lymphatic vessel density correlates with overexpression of VEGF-C in gastric cancer

Lymph node metastasis is one of the most important prognostic factors in malignant tumors. In this study, we investigated vascular endothelial growth factor (VEGF) -C expression in human gastric cancer using immunohistochemical techniques and determined the number of microvessels in peritumoral tissue. VEGF-C expression was positive in 22 of 79 cases (27.8%), and correlated with the presence of lymphatic invasion and lymph node metastasis. We confirmed by reverse transcription-polyrnerase chain reaction (RT-PCR) that VEGF-C mRNA expression is observed more commonly in cancer tissues than normal tissues. For 59 gastric tumors, we examined lymphatic vessel density (LVD) using the specific lymphatic vessel endothelial hyaluronan receptor (LYVE)-1 antibody. VEGF-C expression was observed in 10 of 25 cases (40%) that exhibited a high LVD. Furthermore, high LVD exhibited a significant correlation with VEGF-C expression. Our findings suggest that VEGF-C plays a pivotal role for lymphangiogenesis and tumor growth in gastric cancer.