VEGF-C and VEGF-A Synergistically Enhance Lymph Node Metastasis of Gastric Cancer

Abstract

Vascular endothelial growth factor C (VEGF-C) is the most important molecule in lymphangiogenesis and its relationship with lymph node metastasis has attracted considerable interest. We investigated the relationship of VEGF-C or VEGF-A with clinicopathological factors in gastric cancer patients. Eighty gastric cancer patients who underwent gastric resection were analyzed immunohistochemically for expression of VEGF-C and VEGF-A protein. Positive immunoreactivity of VEGF-C and VEGF-A was observed in 75 (93.8%) and 41 (51.3%) patients, respectively. VEGF-A expression was significantly correlated with tumor differentiation (p=0.0017) and vascular invasion (p=0.0004). And positive relationship of VEGF-C expression was only demonstrated with tumor differentiation (p=0.0168). Interestingly, however, the frequency of lymph node metastasis was significantly higher in the patients with expression of both VEGF-C and VEGF-A (strong positive expression, p=0.036). Furthermore, the expression of both was also significantly correlated with depth of tumor invasion, tumor differentiation, lymphatic invasion, and vascular invasion. The present results suggest that strong expression of VEGF-A in addition to VEGF-C expression is essential in lymph node metastasis, presumably because enhanced metastatic potential including lymphangiogenesis induced by both VEGF-A and VEGF-C is vital in lymph node metastasis of gastric cancer.