Expression of hepatocyte growth factor and c-Met in non-small-cell lung cancer and association with lymphangiogenesis.

ABSTRACT

Previous experimental studies have demonstrated that hepatocyte growth factor (HGF) and its receptor c­Met serve an important function in lymphangiogenesis, but their biological functions in malignant tumors have remained elusive. The present study aimed to investigate the expression patterns of HGF­α and c­Met and their association with vascular endothelial growth factor (VEGF)­C, lymphatic vessel density and lymph node metastasis in non­small­cell lung cancer (NSCLC). In the present study, the lymphatic microvessel density (LMVD) and the expression levels of HGF­α, its receptor c­Met and VEGF­C were determined in 113 human NSCLC tissues and 113 normal lung tissue samples, using immunohistochemical staining. As a result, it was determined that the expression levels of HGF­α, c­Met and VEGF­C were significantly higher in NSCLC tissues than those in normal lung tissues (HGF­α, 67.3 vs. 20.4%, P<0.001; c­Met, 74.3 vs. 23.0%, P<0.001; and VEGF­C, 65.5 vs. 23.9%, P<0.001). HGF­α expression was observed to be significantly associated with that of VEGF­C (r=0.234, P=0.012) or c­Met (r=0.648, P<0.001). In addition, there was a positive correlation between the expression levels of VEGF­C and c­Met (r=0.224, P=0.017). In NSCLC tissues, the expression of HGF­α, c­Met or VEGF­C was significantly correlated with the LMVD (P=0.045, 0.002 and 0.001, respectively), and lymph node metastasis was more common in HGF­α, c­Met or VEGF­C­positive groups (P=0.020, 0.020 and 0.009, respectively). In addition, the HGF­α or VEGF­C­positive groups presented shorter survival time periods. In conclusion, the expression of HGF­α or c­Met was closely correlated with VEGF­C, LMVD and metastases of lymph nodes, indicating that HGF­α, c­Met and VEGF­C may perform important and collaborative actions in lymphangiogenesis and lymphatic metastasis of primary NSCLC.