Objective：To determine the relationship between vascular endothelial growth factor-C (VEGF-C), vascular endothelial growth factor receptor-3 (VEGFR-3, also known as Flt-4) and CNTN-1 (contactin-1) expression in human gastric cancer, as well as the correlation of them with metastatic lymph nodes and other clinicopathologic parameters.
Methods：The samples from primary foci of 37 cases with primary gastric cancer were immunohistochemically examined for VEGF-C, VEGFR-3 and CNTN-1 expressions. Assessment of lymphatic vessel density (LVD) was undertaken. Then we analyzed their relationships and correlations with clinicopathologic findings.
Results：The positivity rate of VEGF-C, VEGFR-3 and CNTN-1 in the primary tumor was 54.05%, 72.97% and 64.16% respectively. The expression of CNTN-1 significantly correlated with VEGF-C (P＜0.05) and VEGFR-3 (P＜0.05). VEFG-C was correlated to TNM stage, lymphatic vessel invasion and lymph node involvement (P＜0.05). CNTN-1 expression was associated with tumor size, TNM stage, lymphatic vessel invasion and  lymph node metastasis (P＜0.05). Higher expression of VEGFR-3 was detected in the patients with advanced TNM stage and lymphatic node metastasis (P＜0.05). Increased level of LVD was significantly associated with later TNM stage,  lymphatic vessel invasion and lymph node metastasis (P＜0.05). LVD was positively correlated with VEGF-C expression (P＜0.05).
Conclusions：High expression of VEGF-C, VEGFR-3 and CNTN-1 was observed in gastric cancer. The expression of VEGF-C correlates with LVD expression and both of them correlate with the presence of lymphatic vessel invasion and lymph node metastasis. VEGF-C-mediated CNTN-1 overexpression might promote lymphatic vessel invasion and lymph node metastasis via lymphangiogenesis pathway in patients with gastric cancer.