Vegf-c, Vegf-d And Its Receptor Expression Of Vegfr-3 In Non - Small Cell Lung Cancer And Relationship With Lymph Node Metastasis

Objective: Both vascular endothelial growth factor (VEGF)-C and (VEGF)-D are ligands of VEGF receptor (VEGFR)-3 (Flt-4) and are supposed to participate in lymphangiogenesis. The purpose of this study was to clarify the clinical significance of the expression of these factors and to evaluate their relationship with lymph node metastasis in patients with non-small cell lung cancer.Methods: The subjects were 62 patients (52 with non-small cell lung cancer and 10 with benign pulmonary lesion). Tissue samples were immediately frozen in liquid nitrogen and stored in it until RNA extraction. A semiquantitative multiplex RT-PCR was designed to compare the RT-PCR products of each VEGF mRNA withβ–actin mRNA products to determine the relative expression. In addition, VEGF-C and VEGFR-3 protein expressions were assessed immunohistochemically.Result: The VEGF-C mRNA level in primary tumors correlated with VEGF-C protein expression,lymph node metastasis. 24 of 25 patients with lymph node metastasis showed VEGF-C mRNA overexpression. The VEGF-C mRNA level in positive lymph node was higher than the negetive. Interestingly, the VEGF-D,VEGFR-3 mRNA level in positive lymph node had significantly lower than the negative (P< 0.05). There was no significant correlation between VEGF-C,VEGFR-3,VEGF-D mRNA and the other clinicopathological factors, including age, gender, T-factor, N-factor ,stage and differentiation. Morphologically, VEGF-C protein expression in primary tumors showed a statiscally significant relationship with lymph nod metastasis. Among the 30 lung cancer specimens,15 cases (50%) had positive results for VEGF-C immunoreactivity in the cytoplasm of cancer cells. In the lung cancer specimen, VEGFR-3 immunoreactivity was present in the cytoplasm of endothelial cells in the small lymphatic vessels. we could not divide tumors into 2 groups on the basis of positive or negative VEGFR-3 immunoreactivity because some of the endothelial cells in the small blood vessels had positive results for VEGFR-3 and weak to moderate VEGFR-3 immunoreactivity was also present in the cytoplasm of some cancer cells.Conclusion: The result of the study indicate that VEGF-C,VEGF-D and VEGFR-3 expression levels can predict lymph node metastasis. They can be a useful predictor of lymph node metastasis in NSCLC.