Expression of hepatocyte growth factor activator inhibitor type 1 in human hepatocellular carcinoma and postoperative outcomes.

Abstract

Hepatocyte growth factor activator inhibitor type 1 (HAI-1), one of the Kunitz-type serine protease inhibitors, has an important role in cancer progression through regulation of the activity of hepatocyte growth factor. HAI-1 is expressed in hepatocellular carcinoma (HCC) to various degrees. Investigation of the relationship between HAI-1 expression and clinicopathological features of HCC may contribute to improved treatment outcomes for HCC through understanding the mechanism of tumor progression or improvement in the prediction of tumor malignancy. The study included 121 HCC patients treated surgically from 1996 to 2005. We performed immunohistological examination for HAI-1 in resected HCC specimens by use of anti-human HAI-1 monoclonal antibody. Clinicopathological features, including postoperative overall survival (OS) and disease-free survival (DFS) rates, were compared between the immunoreaction positive and negative groups. The immunoreaction positive group included 38 patients (31%), and the negative group included 83 patients (69%). OS and DFS rates were significantly higher in the HAI-1 negative group than in the positive group. HAI-1 positivity related to multiplicity, vascular invasion, and characteristics of advanced tumor stage. In multivariate analysis, expression of HAI-1 was a significant independent prognostic tumor factor. Expression of HAI-1 in HCC cells is associated with poor prognosis for HCC patients. HAI-1 may be important in HCC progression and may be a new prognostic factor for HCC.