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Open Access Research article

Expression of ezrin is associated with invasion and dedifferentiation of hepatitis B related hepatocellular carcinoma

Chun-Nan Yeh1, See-Tong Pang2, Tsung-Wen Chen1, Ren-Ching Wu3, Wen-Hui Weng4 and Miin-Fu Chen1*

Author Affiliations

1 Department of Surgery, Chang Gung Memorial Hospital; Chang Gung University, Taoyuan, Taiwan, Republic of China

2 Department of Urology, Chang Gung Memorial Hospital; Chang Gung University, Taoyuan, Taiwan, Republic of China

3 Department of Pathology, Chang Gung Memorial Hospital; Chang Gung University, Taoyuan, Taiwan, Republic of China

4 Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, Taipei City, Taiwan, Republic of China

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BMC Cancer 2009, 9:233  doi:10.1186/1471-2407-9-233

Published: 15 July 2009

Abstract

Background

Hepatocellular carcinoma (HCC) is the fifth most common malignancy in the world and constitutes the leading cause of cancer-related death among men, and second among women in Taiwan. Liver cirrhosis and HCC are relatively prevalent, and 80% to 85% of the patients with these conditions have positive results for hepatitis B surface antigen in Taiwan. Only 5% of the general population is seronegative for all hepatititis B virus (HBV) markers. This is the first study to determine the role of ezrin upon HBV HCC cell and patients with HBV HCC undergoing hepatectomy

Methods

Immunohistochemical study with ezrin in 104 human HBV-HCC cases were carried out to investigate its association with the clinicopathological features and the outcomes of 104 HBV-HCC patients undergoing hepatetomy. In addition, DNA constructs including the wild type ezrin (wt-ezrin) and mutant ezrin Tyr353 (Y353) were transfected into Hep3B cell to study its role in tumor invasion and differentiation.

Results

HBV HCC patients with ezrin over-expression independently have smaller tumor size, cirrhotic liver background, poor tumor differentiation, and more vascular invasion. Ezrin expression status has no impact on survival for HBV-HCC patients undergoing hepatectomy. The in vitro assay showed that wt-ezrin Hep3B cells have a significant higher level of AFP secretion and higher invasion ability as compared with the control and Y353- ezrin Hep3B cells.

Conclusion

Ezrin over-expression contributed to de-differentiation and invasion of HBV-HCC cell. HBV-HCC patients with ezrin over-expression were independently associated with tumor with smaller size, cirrhotic liver background, poor differentiation, and vascular invasion.