Association between VEGFR-3 expression and lymph node metastasis in non-small-cell lung cancer

Abstract

Vascular endothelial growth factor receptor (VEGFR)-3 is considered to be associated with lymphangiogenesis. The aim of the present study was to identify the clinical significance of VEGFR-3 expression and lymph node metastasis in patients with non-small-cell lung cancer (NSCLC). Lung tumor tissue samples and 196 lymph nodes from 52 patients with NSCLC were analyzed. In addition, lung tissue samples and 8 lymph nodes from 10 patients with lung diseases other than cancer were included as controls. Semiquantitative multiplex reverse transcription technology was applied to measure the mRNA expression levels of VEGFR-3, while VEGFR-3 protein expression levels were assessed immunohistochemically. The total number of lymphatic vessels was counted and the microlymphatic vessel density (MLVD) was calculated. The results indicated that the VEGFR-3 mRNA expression level in lymph node tissue from the group with lymph node metastasis was significantly lower compared with the group without lymph node metastasis (0.281±0.166 vs. 0.158±0.158; t=4.849; P<0.001). The VEGFR-3 mRNA expression levels in the lung tumor tissue of the NSCLC patients exhibited no statistically significant difference between the lymph node metastasis and lymph node non-metastasis groups (0.139±0.137 vs. 0.142±0.123; t=0.08; P>0.05). In addition, in the lymph node metastasis group, there was no statistically significant difference between the metastasis-positive and -negative lymph nodes (0.158±0.158 vs. 0.123±0.115; t=0.993; P>0.05) with regard to VEGFR-3 mRNA expression. Morphologically, VEGFR-3 immunoreactivity was primarily localized in the cytoplasm of the lymphatic endothelial cells, as well as a number of the cancer cells. MLVD was much higher in the lung tissue surrounding the tumor than in the tumor tissue, and was significantly higher in the lymph node metastasis group than in the lymph node non-metastasis group. VEGFR-3 expression levels were shown to correlate with lymph node metastasis in NSCLC patients, thus, may be a useful biomarker for lymph node metastasis prediction in NSCLC. MLVD is a key indictor of lymphatic vessel metastasis in NSCLC. An enhanced MLVD indicates lymphangiogenesis and lymphatic node metastasis, and may be an important predictor for tumor monitoring and prognosis.