FAK Ezrin和PTEN蛋白的表达与肝癌生物学行为的关系

Significance of FAK,Ezrin,and PTEN Expression in Hepatocellular Carcinoma

目的: 探讨肝癌中Ezrin、FAK和PTEN的表达及其与肝癌发生及进展的关系。方法:应用免疫组织化学SP法原位观察上述3个蛋白在正常肝组织、肝癌及相应癌旁组织中的表达,分析其与各临床病理参数间的关系。结果:1)Ezrin、FAK和PTEN在肝癌中的阳性表达率分别为66.00%、48.00%及64.00%。2)Ezrin和FAK在肝癌组织中的阳性表达率明显高于正常肝组织(P<0.05,P<0.01),PTFN则相反,其在肝癌组织中的阳性表达率明显低于相应的癌旁组织及正常肝组织(P<0.01)。Ezrin和PTEN的表达均与肝癌的组织分级、血管浸润及卫星灶有关(P<0.05,P<0.01)。FAK的表达与血管浸润及卫星灶有关(P<0.05,P<0.01),但与组织学分级及肝硬化无关。Ezrin、FAK及PTEN的表达均与患者的年龄、性别和肿瘤大小无关(P>0.05)。3)Ezrin与FAK的表达呈正相关(r=0.445,P=0.001),Ezrin和FAK均与PTEN的表达呈负相关(r=-0.475,P=0.001;r=-0.364,P=0.009)。结论:Ezrin和FAK过表达与PTEN表达的下调,可能在肝癌的发生和浸润过程中扮演重要角色。三者的异常表达可能是肝癌发生的一个信号。

Objective： To investigate the protein expression of the membrane cytoskeleton cross linker protein （Ezrin）, focal adhesion kinase （ FAK ）, and phosphates and tensin homolog deleted on chromosome ten （ PTEN ） in hepatocellular carcinoma （HCC） and determine their relationships. Methods： The expression profiles of Ezrin, FAK, and PTEN in 20 cases of normal liver tissues, 50 cases of HCC, and adjacent hepatic tissues were investigated in situ via SP immunohistochemistry （ IHC ）. The relationship between the expression profile and the biological behavior of HCC development and invasion was also analyzed. Results： The protein expression levels of Ezrin and FAK were significantly higher in HCC than in normal liver tissues （ P 〈 0.05 and P 〈 0.01, respectively ）. At a high Ezrin concentration, an FAK expression level was observed in 33 （ 66.0% ） HCC and 24 （ 48.0% ） normal cases. The strong expression of Ezrin （ P 〈 0.05 ） and FAK （ P 〈 0.01 ） were significantly correlated with histological grade, vascular invasion, and HCC satellite lesions. On the other hand, in 32 ot 50 cases （ 64.0% ）, a significantly lower PTEN level was found in the HCC tissue compared with those of adjacent hepatic tissues and normal liver tissues （ P 〈 0.01 ）. No correlation between histological grade and liver cirrhosis was observed, even though the expression level of FAK was associated with vascular invasion and satellite lesions （ P 〈 0.05 or P 〈 0.01 ）. Furthermore, no correlation between the Ezrin, FAK, and PTEN expression levels and patient age, gender, and tumor size was observed （ P 〉 0.05 ）. A significant positive relationship was found between Ezrin and FAK expressions （ r = 0.445, P = 0.001 ）, and an inverse correlation was detected between the expression of Ezrin and PTEN （ r= 0.475, P = 0.001 ） and FAK and PTEN （ r = -0.364, P = 0.009 ）. Conclusion： Further studies need to be conducted to fully understand the strong expression of Ezrin and FAK, the weak expression of PTEN, and the underlying mechanism of HCC invasion and metastasis. In addition, a novel association between the abnormal expression of Ezrin, PTEN, and FAK and hepatocarcinogenesis possibly exists.