Expression of Vascular Endothelial Growth Factors C and D Correlates with Lymphangiogenesis and Lymph Node Metastasis in Lung Adenocarcinoma

Background: Vascular endothelial growth factors (VEGF)-C and -D have been reported to be lymphspecific growth factors. In this study we analyzed the intra- and peritumoral microlymphatic vessel density (MLVD) and the expression of VEGF-C and -D in lung adenocarcinoma. Methods: Tissue samples were obtained from 48 patients who underwent surgery for lung adenocarcinoma. The expression of VEGF-C, -D and MLVD was examined by immunohistochemistry, and the correlation with lymph node metastasis and clinicopathological features was evaluated. Results: Immunohistochemical analysis revealed the presence of VEGF-C and -D immunoreactivity in 70.8% (34/48) and 58.3% (28/48) of the tissue samples, respectively. The group with a high expression of VEGF-C and -D in the tumor margins had a higher incidence of lymph node metastasis. MLVD in both the VEGF-C and the VEGF-D positive groups was higher than that in the negative groups, and the lymph node metastasis was likewise higher. Conclusion: VEGF-C and -D may play important roles in lymphangiogenesis and lymph node metastasis in lung adenocarcinoma.