Cytoplasmic hepatocyte growth factor immunoreactivity predicting lymph node metastasis in esophageal squamous cell carcinoma

Abstract

Esophageal squamous cell carcinoma (ESCC) is a highly malignant disease because of its aggressive biological behavior and metastatic potential. Although several molecular markers have been identified as prognostic factors and/or clinicopathological correlation for the patients of ESCC, it has not been established as the effective new treatment for ESCC patients yet. Hepatocyte growth factor (HGF) is a biomarker as known to promote cell proliferation, motility, and invasion in various human malignancies. But the correlation with cytoplasmic HGF and ESCC has been unclear in details. We studied the correlation of HGF expression in ESCC tumor cells from 83 ESCC patients who were operated in our hospital using immunohistochemistry. High cytoplasmic HGF expression was detected in 50.6 % (42/83) of ESCC cases examined. HGF immunoreactivity was also focally detected in some cancer-associated fibroblasts. High HGF expression group was significantly correlated with lymph node metastasis (P = 0.029) and tumor differentiation (P = 0.018). Increased HGF immunoreactivity was also correlated with clinicopathological features associated with invasiveness of carcinoma cells (lymphatic invasion, venous invasion, distant metastasis, and pathological stage) but not with actual clinical outcome of the patients. Results of our present study indicated that HGF cytoplasmic expression in ESCC was associated with increased potential for lymph node metastasis and carcinoma differentiation. These findings indicated that endogenous HGF did play an important role in progression and invasion of ESCC via c-Met/HGF autocrine loop together with HGF paracrine mechanisms.