The Expression of VEGF-C and It’s Receptor VEGFR-3 Correlates with Lymph Node Metastasis in Gastric Cancer

Abstract

Background: Regional lymph node invasion and metastasis may happen early during the progres-sion of gastric cancer. The lymphadenectomy is still the key method to treat lymph nodemetastasis. In the recent years, scientists have found some growth factors and receptors that can promote angiogenesis which also play an important role in adjusting the formation of the new lymph vessel, and lymphangiogenesis may play a key role in the process of lymph node metastasis. Objectives: This study aims to explore the correlation between the expression of vascular endothelial growth factor-C (VEGF-C), vascular endothelial growth factor receptor 3 (VEGFR-3) and lymph node me-tastasis (LNM), and its impact on prognosis of patients with gastric cancer. Methods: The samples were collected from gastric cancer database of Sichuan Provincial People’s Hospital from 2005 to 2007, which were registered and followed up. The samples were divided into two groups according to situation whether there is lymph node metastasis, which is lymph node metastasis N(+) and without lymph node metastasis N(﹣). The expression of VEGF-C, VEGFR-3 and CD34 were measured by immuno histochemistry staining with monoclonal antibody (anti-VEGF-C, anti-VEGFR-3, and anti-CD34). Kaplan-meier, logistic and Cox regression was performed to explore their impact on the prognosis of patients with gastric cancer. Results: In total 186 cases were collected, 96 cases in N(+) group and 90 cases in N(﹣) group. The percentage of VEGF-C expression is 54.83% (102/186) in all groups, 73.9% (71/96) in N(+) group, and 34.44% (31/90) in N(﹣) group ( p = 0.001). The percentage of VEGFR-3 expression is 33.33% (62/186) in all groups, 44.78% (43/96) in N(+) group, and 21.11% (19/90) in N(﹣) group ( p = 0.001). There are no statistical differences in microvessel density (MVD) between N(﹣) and N(+) group. The average lymphatic vessel density (LVD) was significant different between N(+) and N(﹣) group (26.23 ± 8.2 and 18.46 ± 7.4, t = ﹣2.427, p = 0.016). The five-year overall survival rate of N(+) group is 31% and the N(﹣) group is 66%; there are statistical differences between the two groups (Log rank = 27.15, p = 0.001). The five-year overall survival rates of VEGF-C positive group and VEGF-C negative group are 36% and 59%, with the statistical differences (Log rank = 27.15, p = 0.001). And the five-year overall survival rates of VEGFR-3 positive group and VEGFR-3 negative group are 31% and 43%, also with the statistical differences (Log rank = 5.241, p = 0.041). Conclusions: The expressions of VEGF-C, VEGFR-3 in cell plasma of gastric cancer tissue not only correlate with lymphatic vessel density and lymph node metastasis (LNM), but also are important factors which impact prognosis of gastric cancer patients.