cPTEN+蛋白的表达与肝癌生物学行为的关系

FAK Ezrin 和PTEN 蛋白的表达与肝癌生物学行为的关系*

黄海花①

吴秀浅②郑志超①张薇①

摘要

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），PTEN 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。

关键词

肝细胞肝癌免疫组织化学骨架连接蛋白粘着斑激酶浸润

doi:10.3969/j.issn.1000-8179.2011.14.004

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

Haihua HUANG 1,Xiuqian WU 2,Zhichao ZHENG 1,Wei ZHANG 1

Correspondence to:Xiuqian WU,E-mail:wuxiuqian7311@

1Department of Pathology,Second Affiliated Hospital of Shantou University Medical College,Shantou 515041,China 2

Department of Interventional Therapy,Tumor Hospital of Medical College of Shantou University,Shantou 515041,China

This work was supported by a grant from the Key Technology Projects in Shantou City (No.shan Fu Ke[2009]No70-2)

Abstract

Objective:To investigate the protein expression of the membrane cytoskeleton cross linker protein (Ezrin),focal adhe-

sion 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 20cases of normal liver tissues,50cases of HCC,and adjacent hepatic tissues were investigated in situ via SP immunohistochemistry (IHC ).The relationship between the ex-pression profile and the biological behavior of HCC development and invasion was also analyzed.Results:The protein expression lev-els of Ezrin and FAK were significantly higher in HCC than in normal liver tissues (P <0.05and P <0.01,respectively ).At a high Ez-rin 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 le-sions.On the other hand,in 32of 50cases (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 <0.05or 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 expres-sion 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.

Keywords

Hepatocellular carcinoma;Immunohistochemistry;Ezrin;Focal adhesion kinase;Invasion

作者单位：①汕头大学医学院第二附属医院病理科（广东省汕头市515041）；②汕头大学医学院附属肿瘤医院介入科 本文课题受汕头市重点科技计划项目（编号：汕府科［2009］70号-2）资助

我国是肝癌的高发区，2008年男性的发病率是

37.4/10万人，女性为13.7/10万人［1］。该肿瘤具有发

病率高、进展快、转移早及预后差等特点。治疗方法

主要采用以外科手术为主的综合治疗模式［2］，

虽然通过外科手术有效的提高了患者的生存率，但肝癌术后的复发及转移率仍然较高［3］，即使是小肝癌也存在这个问题。因此肝癌的治疗需要新的思路和方法，这一切有赖于对肝癌发生及侵袭转移机制研究的突