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

Among the mechanisms that control cancer progression, cell mobility is a significant factor required for cellular liberation from the primary focus and infiltration. Hepatocyte growth factor (HGF) has been shown to facilitate cell mobility. In the present study, the clinical significance of the HGF/c-Met pathway in the assessment of gastric cancer progression was evaluated. From a cohort of patients with gastric cancer who underwent surgical resection between April 1999 and March 2003, 110 subjects were randomly selected. Preoperative serum HGF levels were measured and various pathological factors were analyzed. Furthermore, 50 subjects were randomly selected from within this group and immunohistochemical staining of tissue preparations for HGF and its receptor c-Met were performed. In the infiltrative growth pattern [(INF)α,β vs. INFγ], advanced progression was associated with elevated preoperative serum HGF levels (P<0.001). No correlation was identified between serum HGF levels and immunostaining for HGF or c-Met in the tissue preparations. Immunostaining revealed a significant correlation between c-Met expression and lymphatic vessel invasion (ly0.1 vs. 2.3; P=0.0416), lymph node metastasis (n0.1 vs. 2; P=0.0184) and maximum tumor diameter (≤50 mm vs. >50 mm; P=0.0469). Furthermore, c-Met-positivity was associated with a significant difference in overall survival (P=0.0342), despite stage I and II cases accounting for 82% of the total cohort (41 of 50 cases). These results suggested that the expression of the HGF/c-Met pathway in gastric cancer may be a potential predictive factor for disease progression.