膀胱移行细胞癌中FHIT基因异常甲基化及其与临床病理学的关系

目的检测FHIT基因在膀胱移行细胞癌中的异常甲基化及其表达,探讨其与膀胱移行细胞癌临床病理学的关系。方法收集膀胱移行细胞癌新鲜组织标本共49例和10例正常膀胱组织,采用免疫组织化学的方法(S-P法)检测FHIT蛋白表达,用甲基化特异性聚合酶链反应PCR(MS-PCR)方法研究膀胱移行细胞癌组织、正常膀胱组织中FHIT基因启动子区CpG岛甲基化状态。结果FHIT蛋白在正常膀胱组织均为阳性;FHIT蛋白在膀胱移行细胞癌中阳性表达率为47%(23/49),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～T1期与T2～T4期比较,差异无统计学意义(P>0.05)。49例膀胱移行细胞癌组织中,有8例发生了甲基化,阳性率为16%(8/49)。FHIT基因的异常甲基化和蛋白表达无相关性。正常膀胱组织FHIT基因启动子甲基化频率0(0/10)。结论FHIT基因与膀胱移行细胞癌的发生发展有关,FHIT蛋白异常表达可作为膀胱移行细胞癌肿瘤标志物。FHIT基因甲基化及表达缺失参与膀胱移行细胞癌的发生发展,且与其临床病理有一定关系,可能是影响膀胱移行细胞癌预后的重要因素。

Clinicopathological significance of aberrant methylation of the fragile histidine triad in bladder transitional cell carcinoma

Objective To investigate the aberrant methylation of fragile histidine triad (FHIT) gene and to explore possible relationship between the aberrant methylation of FHIT and clinicopathological features in bladder transitional cell carcinoma (HCC). Methods The expression of FHIT was studied by S-P immunohistochemisty in 10 cases of normal urinary bladder tissues and 49 cases of bladder transitional cell carcinoma. The promoter methylation status was tested by methylation-specific PCR. Results All the normal urinary bladder tissues showed positive staining pattern of FHIT protein; 46.9%(23/49) of bladder transitional cell carcinomas (TCC) showed positive staining pattern of FHIT protein, the expression of FHIT protein decreased with the high grade, and 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). The frequencies of hepermethylation of FHIT in normal urinary bladder tissue and bladder transitional cell carcinoma were 16.3%, and 0 respectively. The methylation of FHIT gene is negative-related with the grade of bladder transitional cell carcinoma (P<0.05). The hepermethylation of FHIT gene is no-related with the expression of FHIT protein(P>0.05). Conclusion FHIT gene is related to occurrence and development of the bladder TCC. It can be regarded as a new useful diagnostic marker in the bladder TCC. Hepermethylation of FHIT may play a different role in the bladder TCC, it might play an important role in the prognosis of TCC.