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


CONCLUSIONS
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.
Yeh
Chun-Nan
CN
Department of Surgery, Chang Gung Memorial Hospital; Chang Gung University, Taoyuan, Taiwan, ROC. ycn@adm.cgmh.org.tw
Pang
See-Tong
ST
Chen
Tsung-Wen
TW
Wu
Ren-Ching
RC
Weng
Wen-Hui
WH
Chen
Miin-Fu
MF
D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000150:complications* / Q000378:metabolism; D002454:Cell Differentiation; D003598:Cytoskeletal Proteins / Q000096:biosynthesis*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D006498:Hepatectomy; D006509:Hepatitis B / Q000150:complications* / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000150:complications* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009361:Neoplasm Invasiveness; D016896:Treatment Outcome; D000099149:Ezrin
D003598:Cytoskeletal Proteins; D000099149:Ezrin