| Objective: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and the third leading cause of cancer deaths in the world. China has a high incidence of HCC, and HCC is one of the deadliest cancers, the mortality rate of HCC occupies 43.7 percent of the world death toll. In recent years, trends in Age-adjusted incidence rate(AAIR) rises up and that ranges from age 30 to 44 dead from liver cancer occupies the first place among all of the malignant tumors death. Therefore, research on prevention and therapy of HCC is a key point in nowadays and in the future. Until today, surgery is still the main methods to cure liver cancer. Section, resection and interventional therapy become the mature therapy pattern. But the usual outcome is still very poorly, 5-year survival rate is much lower than the 1-year survival rate because of early metastasis and recurrence after surgery. So it is important to study the mechanism of hepatocarciogenisis, recurrence and metastasis on HCC.Ezrin is product of Vil12 which located at anthropo-chromosome 6q25. 20 years ago, Bretscher, found that ezrin is the main component of the brush border cytoskeleton of small intestine. Some recent research indicates that ezrin plays a crucial role in the metastasis of some pediatric tumors. With more and more evidence in experimental and clinical work show that ezrin and cell adhesion molecules are important substance which affect cell adhesion and malignancy progression. Recent studies suggent many tumors express ezrin, but the role of ezrin in the hepatocarciogenesis and its progression is poorly understood. So our study aims to test ezrin expression in normal liver tissue, liver cirrhosis tissues, HCC tissues and para-cancerous tissues, to understand their difference of expression, to explore the mechanism of ezrin in hepatocarciogenisis and its progression and metastasis.Methods: The whole study has two parts.1. The first part: The study of ezrin expression and it,s clinical significance in human hepatocellular carcinoma 61 cases of liver tissue were selected from removed and biopsied liver tissue from 2005.1 to 2007.8 in the third affiliated hospital of hebei medical university, including 30 cases of HCC diagnosed by pathology, 23 cases of liver cirrhosis, 8 cases of normal hepatic tissue selected from hemangiomas of liver. Immunohistochemical technique was used to estimate the expression of ezrin.2. The second part: The study of ezrin expression and it,s clinical significance in mice hepatocellular carcinoma75 male kunming mice were divided into three groups, weight 18 to 22 grams, 15 cases in normal mice group, 35 cases in HCC group and 25 cases in liver cirrhosis group. The mouse in liver cirrhosis Group was fed solution 0.2 ml with 10% of carbon tetrachloride olive oil gavage, four times a week for 16 weeks, until hepatic Lobules disappear with a pathological false lobules form. The mouse in the HCC model group were injected 5×106 H22 Hepatoma cell into liver along the length the horizontal axis and a 30-degree angle into the liver. Ezrin expression were Observed in tumor tissues on the 7th, 14th, 20th days after injection and the difference of expression were analysis by immunohistochemistry.Results: 1.Using the SP method of immunohistochemistry to test the ezrin expression in 8 cases of normal human liver samples, 30 cases of HCC samples, 30 cases of Para-carcinoma samples and 23 cases of liver cirrhosis samples, and the results show as below: the positive staining rates of ezrin in the HCC samples is 86.67%(26/30), and it is obviously higher than that of normal liver samples, liver cirrhosis samples and Para-carcinoma samples, which is 25.00%(2/8), 43.48%(10/23) and 56.67%(17/30) respectively, The difference of strong ezrin express between the 4 groups has statistic significance(p<0.01). The positive staining rates of ezrin in the poor differentiation HCC samples is 50.00%, and it is obviously higher than that of in high and middle degree which is 14.28% and 20%. The difference of strong ezrin express between the three groups has statistic significance (χ2 = 153.72 to 157.9, P <0.01). The positive staining rates of ezrin in the HCC samples greater than 3 cm is 41.18%, and it is obviously higher than that of less than or equal to 3 cm diameter, which is 22.22%. The difference of strong ezrin express between the two groups has statistic significance (χ2 = 144.60, P <0.01). The positive staining rates of ezrin in the transfer HCC samples is 66.67%, and it is obviously higher than that of no transfer group which is 16.06%, the difference of strong ezrin express between the two groups has statistic significance (χ2 = 144.67, P <0.01).2.Using the SP method of immunohistochemistry to test the ezrin expression in 14 cases of normal mice liver samples, 28 cases of HCC samples and 23 cases of liver cirrhosis samples, and the results show as below: the positive staining rates of ezrin in the HCC samples is 89.28%, and it is obviously higher than that of normal liver samples, liver cirrhosis samples, which is 14.28% and 40% respectively, The difference of strong ezrin express between the three groups has statistic significance (p<0.01). The positive staining rates of ezrin in the 20th day HCC samples is 80.00%, and it is obviously higher than that of the 7th, 14th day HCC samples, which is 33.33% and 55.56% respectively, The difference of strong ezrin express between the three groups has statistic significance(χ2=163.82～165.00,P<0.01).Conclusions: The expression of ezrin is ralated to the vicious development of hepatoma carcinoma cell. Ezrin can sustain special structure of cellular membrane surface, control cellular form, participate in cell adhesion, take part in signal transduction through Rho-GTP and AKT-mediated apoptosis mechanism which take a chance for carcinogenesis, but the complicate mechanism is to be explored in the future.
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