贲门腺癌中RASSF1A基因甲基化与cyclin D1表达的关系  

Relationship between RASSF1A gene methylation and the expression of cyclin D1 in gastric cardiac adenocarci-noma

作　　者：郭炜[1] 杨植彬[1] 范立侨[2] 邝钢[1] 董稚明[1] 

机构地区：[1]河北医科大学第四医院肿瘤研究所病理研究室,石家庄050011 [2]河北医科大学第四医院外三科,石家庄050011

出　　处：《肿瘤》2009年第2期164-167,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:探讨贲门腺癌(gastric cardiac adenocarcinoma,GCA)中RASSF1A基因的甲基化状态及其与cyclinD1蛋白表达之间的相关性。方法:分别应用甲基化特异性PCR(mothylation-specific PCR,MSP)方法和免疫组织化学SP法检测贲门腺癌组织及相应癌旁组织的RASSF1A基因甲基化情况和cyclin D1蛋白表达情况。结果:92例贲门腺癌组织中有54例RASSF1A发生了甲基化,甲基化率为58.7%,显著高于癌旁正常组织(P<0.001)。Ⅲ期和Ⅳ期贲门腺癌患者中RASSF1A基因发生甲基化的比率显著高于Ⅰ期和Ⅱ期患者(P<0.05)。92例贲门腺癌组织中有72例(78.3%)cyclin D1蛋白表达阳性,与相应癌旁正常组织比较,cyclin D1在贲门癌组织中的表达显著升高(P<0.001);且随肿瘤分化程度的降低,cyclin D1的阳性表达率明显升高(P<0.05)。RASSF1A基因在贲门腺癌中的高甲基化与cyclinD1蛋白表达之间有明显的相关性(P<0.05)。结论:RASSF1A基因启动子区的高甲基化以及cyclin D1蛋白的过表达可能参与了贲门腺癌的发生发展过程。Objective：To investigate the relationship between RASSF1A gene methylation and the expression of cyclin D1 in gastric cardiac adenocarcinoma （GCA）. Methods：The methylation of the 5＇ CpG island of RASSF1A was detected by methylation-specific PCR （MSP） and the expression of cyclin D1 was determined by immunohistochemical method in GCA tissues and corresponding paracancerous normal tissues. Results：RASSF1A was methylated in 54/92 （58.7%） tumor specimens, which was significantly higher than that in corresponding normal tissues （P 〈 0. 001 ）. Methylation frequencies of stages Ⅲ and IV tumor tissues were significantly higher than those in stage Ⅰ and Ⅱ tumor tissues （P 〈 0.05）. Positive immunostaining of cyclin D1 was detected in 72/92 （78.3%） tumor tisssues, which was significantly higher than that in corresponding normal tissues （P 〈0. 001 ）. The positivity of cyclin D1 was significantly increased with the decrease in the differentiation degree of GCA （P 〈0.05 ）. Hypermethylation of RASSF1A was correlated with the expression of cyclin D1 in GCA （P 〈 0.05 ）. Conclusion： The hypermethylation in the promoter region of RASSF1A gene and overexpression of cyclin D1 may be involved in the tumorigenesis and progress of GCA.

关 键 词：胃肿瘤 贲门 DNA甲基化 基因 肿瘤抑制 细胞周期蛋白D1 基因  RASSF1A 

分 类 号：R735.2[医药卫生—肿瘤]