Correlation between lymph node metastasis and the expression of VEGF-C, VEGF-D and VEGFR-3 in T1 lung adenocarcinoma.

Vascular endothelial growth factor (VEGF)-C and VEGF-D influence lymphangiogenesis through the activation of the vascular endothelial growth factor receptor (VEGFR)-3. They have been implicated in lymphatic tumor spread, which is an important prognostic factor in patients with non-small cell lung carcinoma (NSCLC). Whether or not the expression of VEGF-C, -D, and VEGFR-3 correlates with clinicopathological factors in patients with T1 lung adenocarcinoma was analysed. The tumor specimens were homogenized to determine the protein expression of VEGF-C, -D, and VEGFR-3 by enzyme-linked immunosorbent assay (ELISA). RNA fractions extracted from the tumor tissues were subjected to real-time reverse transcription-polymerase chain reaction (RT-PCR) to assess the mRNA levels of VEGF-C, -D, and VEGFR-3. The expression of VEGF-D protein and mRNA levels in patients without lymph node metastasis were significantly higher than those with metastasis (p=0.013, p=0.0494, respectively). However, the protein and mRNA levels of VEGF-C and VEGFR-3 were not significantly different in patients with or without metastasis. The 5-year survival rates of the patients with high VEGF-D levels were significantly higher than those of patients with low levels (p =0.0221). No significant difference in the survival rates was observed for VEGF-C and VEGFR-3. VEGF-D may be downregulated in NSCLC tissues in comparison to adjacent normal tissue, resulting in lymph node metastasis and poor prognosis.