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 agematched 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 cMet levels contributes to the prognostic evaluation of tumor progression in the preoperative period. Furthermore, it is likely that HGF oversupply-associated cMet downregulation occurs in colorectal cancer via autocrine, paracrine and endocrine mechanisms.

Clinical significance of hepatocyte growth factor/c-Met expression in the assessment of gastric cancer progression

“…Three fields of each section were observed at 200× magnification using a BHS/System Living microscope (Olympus Corp., Tokyo, Japan) and the results were classified as positive when the ratio of stained cancer cells was >25%, according to previous studies that were analyzed for comparison ( Fig. 1 ) ( 8 , 29 – 31 ).…”

“…In a previous study by our group, an association between elevated pre-operative serum HGF levels and advanced disease stages in colon cancer was identified, mainly regarding the depth of tumor invasion into the wall and liver metastasis, which suggested the expression of the HGF/c-Met pathway as a potential predictive factor of colon cancer progression ( 8 ). In the present study, serological and immunohistological analyses were conducted in order to evaluate the clinical significance of the expression of the HGF/c-Met pathway in assessing the stage of gastric cancer progression.…”

“…Among the mechanisms that mediate cancer progression, cell mobility is a significant factor necessary for liberation from the primary focus and infiltration. Various cell growth factors ( 1 – 5 ), including epidermal growth factor, transforming growth factor β ( 6 , 7 ) and hepatocyte growth factor (HGF) ( 8 ), are known to facilitate cell mobility.…”

Clinical significance of fibronectin expression in colorectal cancer

“…Investigating the relationship between CRC and HGF and mesenchymal epithelial transition factor (c-Met), we found higher preoperative levels of expression of circulating HGF/c-Met in patients with hepatic metastases. The results of the immune staining were, however, unpredicted, demonstrating increased expression of HGF and decreased expression of c-Met as disease staging progressed (6). Our present understanding of this phenomenon suggests that the production of HGF by both paracrine and endocrine mechanisms leads to the supersaturation and downregulation of c-Met (6).…”

“…The results of the immune staining were, however, unpredicted, demonstrating increased expression of HGF and decreased expression of c-Met as disease staging progressed (6). Our present understanding of this phenomenon suggests that the production of HGF by both paracrine and endocrine mechanisms leads to the supersaturation and downregulation of c-Met (6). In another study, we found that TGF-ß1 expression within CRC tissue was significantly higher in patients with lymphatic metastases and high-grade venous infiltration, and that serum TGF-ß1 levels were also significantly higher in patients with CRC than in the controls.…”