Association between expression of vascular endothelial growth factor c, chemokine receptor CXCR4 and lymph node metastasis in colorectal cancer

Objectives: Lymph node metastasis is one of the determining factors of a poor prognosis for colorectal cancer. Recent studies have reported that cancer cells can promote lymphangiogenesis and that chemokine receptors expressed by cancer cells might play a role in metastasis. In this study, we examined the correlation between the expression of vascular endothelial growth factor ( VEGF) C, the chemokine receptor CXCR4 and lymph node metastasis in colorectal cancer. Methods: One hundred and sixty- one consecutive patients who underwent resection at our department were studied. Lymph node metastasis was observed in 69 cases ( 43%) and lymphatic involvement was present in 105 cases ( 65%). Immunohistochemical staining was performed using antibodies for VEGF- C and CXCR4. Moreover, lymphatic vessel density ( LVD) was evaluated within the tumor by immunostaining with a D2- 40 antibody. Results: VEGF- C expression was found in 81 cases ( 50%) and CXCR4 expression in 87 cases ( 54%). Regarding the correlation between nodal metastasis and the expression of CXCR4 and VEGF- C, the incidence of nodal metastasis was significantly ( p < 0.01) higher in patients with CXCR4- positive tumors than in those with CXCR4- negative tumors. In addition, a significant correlation was observed between CXCR4 and VEGF- C expression and lymphatic invasion ( p < 0.01). LVD was significantly higher in VEGF- C- positive tumors compared with VEGF- Cnegative tumors. However, there was no significant correlation between LVD and CXCR4 expression. Using multivariate analysis, VEGF- C, CXCR4, lymphatic invasion and wall invasion were found to be independent risk factors for lymph node metastasis. Conclusions: This study suggests that although the mechanism that promoted lymph node metastasis was different between VEGF- C and CXCR4, both VEGF- C and CXCR4 contributed to lymphatic involvement and nodal metastasis in colorectal cancer.