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

Previous experimental studies have demonstrated that hepatocyte growth factor (HGF) and its receptor c-Met 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 HGF-α and c-Met and their association with vascular endothelial growth factor (VEGF)-C, lymphatic vessel density and lymph node metastasis in non-small-cell lung cancer (NSCLC). In the present study, the lymphatic microvessel density (LMVD) and the expression levels of HGF-α, its receptor c-Met and VEGF-C 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 HGF-α, c-Met and VEGF-C were significantly higher in NSCLC tissues than those in normal lung tissues (HGF-α, 67.3 vs. 20.4%, P<0.001; c-Met, 74.3 vs. 23.0%, P<0.001; and VEGF-C, 65.5 vs. 23.9%, P<0.001). HGF-α expression was observed to be significantly associated with that of VEGF-C (r=0.234, P=0.012) or c-Met (r=0.648, P<0.001). In addition, there was a positive correlation between the expression levels of VEGF-C and c-Met (r=0.224, P=0.017). In NSCLC tissues, the expression of HGF-α, c-Met or VEGF-C was significantly correlated with the LMVD (P=0.045, 0.002 and 0.001, respectively), and lymph node metastasis was more common in HGF-α, c-Met or VEGF-C-positive groups (P=0.020, 0.020 and 0.009, respectively). In addition, the HGF-α or VEGF-C-positive groups presented shorter survival time periods. In conclusion, the expression of HGF-α or c-Met was closely correlated with VEGF-C, LMVD and metastases of lymph nodes, indicating that HGF-α, c-Met and VEGF-C may perform important and collaborative actions in lymphangiogenesis and lymphatic metastasis of primary NSCLC. [ABSTRACT FROM AUTHOR]