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

ABSTRACT

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-C-negative 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.