Expression of Vascular Endothelial Growth Factor D Is Associated with Lymph Node Metastasis in Human Colorectal Carcinoma

Abstract

OBJECTIVE: Expression of vascular endothelial growth factor (VEGF)-D by tumors is associated with metastasis to lymph nodes in mice. However, there are few reports concerning the clinical significance of VEGF-D protein in human carcinoma. METHODS: After confirming production of VEGF-D by eight colorectal carcinoma cell lines, we investigated relationships between the expression of VEGF-D protein, lymph node metastasis and postoperative survival in 83 colorectal carcinoma patients. mRNA levels in cell lines were evaluated using the real-time reverse transcriptase-polymerase chain reaction, and protein was detected by Western blotting in cell lines and by immunohistochemistry in resected tissues using an antibody recognizing the processed form of the molecule. RESULTS: Immunohistochemistry showed VEGF-D-positive staining in 26 of the 83 carcinomas (31%). There was a significant relationship between the presence of VEGF-D protein and the incidence of lymph node metastasis (p < 0.01). Multivariate logistic regression analysis revealed that VEGF-D protein expression was an independent factor affecting lymph node metastasis (p < 0.01). Nonetheless, the presence or absence of VEGF-D protein had no significant impact on the survival of the patients (p = 0.15). CONCLUSION: These results suggest that the expression of VEGF-D protein could be useful in predicting the nodal status of colorectal carcinoma patients.