膀胱移行细胞癌中FHIT基因启动子甲基化及其蛋白的表达

Aberrant Methylation of FHIT Gene Promoter and its Protein Expression in Bladder Transitional Cell Carcinoma

目的:探讨膀胱移行细胞癌(BTCC)FHIT基因启动子甲基化状态及其与FHIT蛋白表达的关系。方法:采用甲基化特异性PCR(MS-PCR)方法及免疫组织化学S-P法检测62例BTCC组织和10例正常膀胱组织中FHIT基因启动子甲基化状态及FHIT蛋白表达。结果:BTCC组织、正常膀胱组织FHIT基因启动子甲基化频率分别为19.4%(12/62),0(0/10)。FHIT蛋白在正常膀胱组织、BTCC中阳性表达率分别为100.0%(10/10)和46.77%(29/62),肿瘤不同分级中随恶性程度的增高,表达减少,Ⅰ级与Ⅲ级比较,差异有统计学意义(P<0.05),不同临床分期中随分期的增高,表达减少,Tis～T_1与T_2～T_4比较,差异无统计学意义(P>0.05)。FHIT基因的启动子甲基化和蛋白阳性表达有相关(P<0.05)。结论:FHIT基因的启动子甲基化可能是基因失活重要机制之一,FHIT基因启动子甲基化及表达在BTCC的发生、发展中起重要作用。

Objective：To study the relationship between aberrant methylation of FHIT gene promoter and its protein expression in bladder transitional cell carcinoma （BTCC）. Methods： Methylation-specific PCR （MS-PCR） and immunohistochemical S-P technique were used to detect the aberrant methylation of FHIT gene promoter and its protein expression in 62 cases of BTCC and 10 cases of normal urinary bladder tissues. Results：The frequencies of FHIT gene promoter in normal urinary bladder tissue and BTCC were 19.4 % （12/62） ,0 （0/10） respectively. The positive rate of FHIT expression in normal urinary bladder tissue and BTCC was 100.0% （t0/10） and 46. 77% （29/62） respectively. The expression of FHIT protein decreased with the high grade. Compared Ⅰ and Ⅲ grade, it had marked statistical significance （P〈0.05）, the difference of positive rate between Tis T1 and T2-T4 cases showed a trend of decreasing, but there was no statistically significant difference （P〉0.05）. There was correlation between methylation of FHIT gene promoter and expression of its protein （P〈0.05）. Conclusions： Abet rant methylation of FHIT gene promoter might be one of important factors of inactivation of FHIT gene. Aberrant methylation of FHIT gene promoter and its protein expression play important role in the occurrence and develop- ment of the BTCC.