贲门腺癌中E-钙黏蛋白基因甲基化状态研究  

Methylation status of E-cadherin gene in gastric cardiac adenocarcinoma

作　　者：郭炜[1] 董稚明[1] 杨植彬[1] 邝钢[1] 于凤玲[1] 高国栋[1] 

机构地区：[1]河北医科大学第四医院省肿瘤研究所病理研究室,石家庄050011

出　　处：《肿瘤》2008年第1期53-56,共4页Tumor

基　　金：河北省科技厅科技攻关项目(编号:052761163);河北省强势特色学科基金资助项目(编号:冀教高[2005]52号)

摘　　要：目的:研究贲门腺癌(gastric cardiac adenocarcinoma,GCA)中E-钙黏蛋白(E-cadherin)的基因甲基化状态及其蛋白表达情况。方法:分别应用巢式甲基化特异性PCR(methylation specific PCR,MSP)方法及免疫组织化学SP法检测贲门癌组织及相应癌旁组织的甲基化和蛋白表达情况。结果:92例贲门癌组织中有63例E-cadherin发生了甲基化,甲基化率为68.5%,显著高于癌旁正常组织(P<0.001);Ⅲ期和Ⅳ期的发生率明显高于Ⅰ期和Ⅱ期患者(P=0.01);低分化腺癌组发生甲基化的比率显著高于中、高分化腺癌组(P<0.01)。92例贲门癌组织中有51例蛋白表达呈明显的异质性,贲门癌组织的E-cadherin蛋白表达率为44.6%,与相应癌旁正常组织相比差异有统计学意义(P<0.001)。Ⅲ期和Ⅳ期患者的蛋白表达明显低于Ⅰ期和Ⅱ期患者(P<0.01);低分化腺癌组的蛋白表达率也低于中、高分化腺癌组,差异有统计学意义(P<0.05)。结论:E-cad-herin基因启动子区发生甲基化导致的基因沉默可能是贲门腺癌发生的机制之一,可作为反映贲门腺癌生物学行为的指标。Objective ： To investigate the methylation status of the promoter of E-cadherin gene and its protein expression in gastric cardiac adenocarcinoma（GCA）. Methods： The methylation status of the 5＇CpG island of E-cadherin was determined by a nested methylation specific PCR approach and E-cadherin protein expression was measured by immunohistochemical method in GCA tissues and adjacent tissues. Results： E-cadherin was methylated in 63 of 92 （68.5%） GCA specimens, which was significantly higher than that in paracancerous normal tissues （ P 〈 0. 001 ）. Methylation occurred more frequently in patients at stage Ⅲ and Ⅳ than those at stage Ⅰ and Ⅱ （ P =0.01 ）. The frequency of methylation was significantly higher in poor differentiated group than moderate and well differentiated groups （ P 〈 0.01 ）. Immunohistochemical staining showed that E-cadherin expression was demonstrated heterogeneous,in 51 of 92 （44.6%） GCA specimens which was significantly different from matched paracancerous normal tissues. The positive rate of E-cadherin protein was significantly lower in patients at stage Ⅲ and Ⅳ than those at stage Ⅰ and Ⅱ （P 〈0.01 ）. The positivity of E-cadherin was markedly lower in poor differentiated group compared with moderate and well differentiated groups, and the difference was significant （ P 〈 0.05 ）. Conclusion ： Gene silencing caused by methylation of the 5＇CpG island of E-cadherin gene may be one of the mechanisms for the tumorigenesis and development of GCA. The methylation status of E-cadherin could be used as a marker indicating the biological behaviors of GCA.

关 键 词：消化系统肿瘤 DNA甲基化 聚合酶链反应 基因 E-钙黏蛋白 

分 类 号：R735.2[医药卫生—肿瘤]