肝细胞癌整合蛋白α5β1、纤维连接蛋白及其降解片段的表达

Expression and detection of integrin α5β1,fibronectin and its fragment in patients with hepatocellular carcinoma.

目的探讨整合蛋白α５β１、纤维连结蛋白（ＦＮ）及其降解片段——恶性疾病相关性ＤＮＡ结合蛋白２（ＭＡＤ２）与肝细胞癌（ＨＣＣ）生物学行为间的关系及血浆ＭＡＤ２检测的意义。方法应用免疫组化及图像分析技术对４０例ＨＣＣ组织作整合蛋白α５β１、ＦＮ和ＭＡＤ２定位和定量分析，并以酶联免疫吸附法检测３０／４０例ＨＣＣ患者血浆中ＭＡＤ２和ＦＮ浓度。结果高分化ＨＣＣ组织整合蛋白α５β１、ＦＮ和ＭＡＤ２表达与正常及癌旁组织相近，而中、低分化ＨＣＣ中三者均明显减弱或消失；肿瘤浸润包膜处三种蛋白表达减少，但血管内癌栓外侧缘癌细胞整合蛋白α５β１和ＦＮ表达较强，并与相应血管内皮的强表达相映。ＨＣＣ患者血浆ＭＡＤ２平均浓度显著高于慢性肝病及正常对照者。结论整合蛋白α５β１和ＦＮ表达可能在ＨＣＣ分化、浸润及转移中起作用；ＨＣＣ患者血浆ＭＡＤ２含量的检测可能有一定临床意义。

Objective\ To study the relationship between the expression of integrin α5β1,fibronectin(FN)and its fragment(malignant disease associated DNA binding protein 2 MAD2)and the biologicbehavior of human hepatocellular carcinoma(HCC)as well as the significance of MAD2 detection in plasma.Methods\ Integrin α5β1,FN and MAD2 were localized by immunohistochemical methods and quantified by image analysis in tumor and peripheral liver tissues from 40 HCC cases.The concentration of FN and MAD2 in the plasma samples from 30/40 cases were examined using the ELISA method.Results\ The expression of integrin α5β1,FN and MAD2 in well differentiated HCC were not significantly different from that of normal tissues,while they were markedly decreased or undetectable in moderately and poorly differentiated HCC.Decr eased expression of integrin α5β1 and FN atsites where HCC invaded the connective tissue and enhanced expression on the HCC cells around cancerous emboli were also noted.The mean concentration of plasma MAD2 in patients with HCC were significantly in crease d when compared to those with chronic liverdisease and normal subjects.Conclusions\ The changes in integrin α5β1 and FN expression may be associated with HCC differentiation,invasi on and metastasis.The detection of plasma MAD2 in patients with HCC may have clinical significance.