Clinical Significance of Hepatocyte Growth Factor and Its Specific Receptor c-Met Expression in Colorectal Cancer Progression

Abstract

To clarify the clinical significance of hepatocyte growth factor (HGF) and its specific receptor c-Met in colorectal cancer, we performed serological analysis of HGF in 108 patients who underwent colon cancer surgery and 200 age-matched control subjects, and immunohistochemical analysis of HGF and c-Met in surgically resected samples in 50 of the 108 patients. Serological analysis demonstrated that preoperative serum HGF level was significantly higher in the cancer group than in the control group (p<0.0001), and increased in patients with advance of depth of invasion (p=0.0173), liver metastasis (p=0.0024), and tumor stage (p=0.0069). Immunohistochemical analysis demonstrated the strong expression and colocalization of HGF and c-Met in the cancer cells. Tissue HGF staining score was increased in patients with advance of venous invasion (p=0.0092), whereas tissue c-Met staining score was decreased in patients with advance of lymphatic invasion (p=0.0234), liver metastasis (p=0.0176), and serum HGF level over 300 pg/mL (p=0.018). The present results suggest that the verification of both preoperative serum HGF level and tissue HGF and c-Met levels contributes to the prognostic evaluation of tumor progression in the preoperative period. Furthermore, it is likely that HGF oversupply-associated c-Met downregulation occurs in colorectal cancer via autocrine, paracrine and endocrine mechanisms.