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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 investigate the promoter methylation status of FHIT gene in bladder transitional cell carcinoma (BTCC) and its relationship with FHIT protein expression. Methods: The methylation status and FHIT protein expression of FHIT gene in 62 BTCC tissues and 10 normal bladder tissues were detected by methylation-specific PCR (MS-PCR) and immunohistochemical S-P method. Results: The promoter methylation frequencies of FHIT gene in BTCC tissues and normal bladder tissues were 19.4% (12/62) and 0 (0/10), respectively. The positive rates of FHIT protein in normal bladder tissues and BTCC were 100.0% (10/10) and 46.77% (29/62), respectively. There was a significant difference in the expression of FHIT protein among the different grades of malignant tumors, The difference was statistically significant (P <0.05). The expression of Tis ~ T 1 and T 2 ~ T 4 in different clinical stages was increased with the increase of staging. There was no significant difference between Tis ~ T 1 and T 2 ~ T 4 (P> 0.05). FHIT gene promoter methylation and protein expression were correlated (P <0.05). CONCLUSION: Promoter methylation of FHIT gene may be one of the important mechanisms of gene inactivation. Methylation and expression of FHIT gene promoter play an important role in the occurrence and development of BTCC.