Hepatocyte growth factor in human esophageal squamous cell carcinomas is an independent prognostic factor

Abstract

Purpose Hepatocyte growth factor/scatter factor (HGF/SF) and its receptor c-Met, play important roles in tumor development and progression. In this study, we measured the serum HGF levels in patients with esophageal squamous cell carcinoma (ESCC) to evaluate its relationships with clinicopathologic features, prognosis, and angiogenic factors.

Experimental design One hundred and forty-nine patients with ESCC were included in the study. Pre-therapy serum was collected and ELISA was used to detect the concentrations of HGF, vascular endothelial growth factor (VEGF) and interleukin 8 (IL-8). HGF and c-Met in tissue specimens and cell lines were assayed by immunohistochemical staining and flow cytometry, respectively.

Results Pre-therapy serum HGF was found to be significantly higher in patients with ESCC than in healthy subjects. The levels of HGF correlated significantly with M stage, advanced TNM stage and survival. Multivariate analyses showed that serum HGF level, TNM stage, surgical resection, and the use of chemoradiation therapy were independent prognostic factors. Increased HGF serum levels also correlated positively with serum levels of VEGF and IL-8. Immunohistochemical staining showed that the onco-protein c-Met was expressed in esophageal tumor cells from esophagectomy specimens and ESCC cell lines, while HGF was mainly expressed by tumor cells and stromal cells such as infiltrated cells, endothelial cells and fibroblasts.

Conclusion Our results suggest that HGF may be involved in the progression of ESCC as a autocrine/paracrine factor. These findings also indicate that serum HGF may be a useful biomarker of tumor progression and a valuable independent prognostic factor in patients with ESCC.