膀胱移行细胞癌微卫星不稳定性及其机制的研究

目的　探讨膀胱移行细胞癌 (BTCC)染色体微卫星不稳定性的表现及与基因突变的关系。方法　采用聚合酶链反应 (PCR)方法检测 4 0例 BTCC患者 5个微卫星位点的改变 ,同时用同样的方法检测癌组织中BAX基因和转化生长因子 (TGF) - β 型受体基因移码突变的情况。结果　至少发生一个微卫星位点改变的阳性率为 82 % (33/ 4 0 ) ,D9S16 2、D16 S4 76、D9S5 4、FGA和干扰素 (IFN) - A1位点改变各自的阳性率分别为 5 8%(2 3/ 4 0 )、 4 2 % (17/ 4 0 )、 38% (15 / 4 0 )、 4 8% (19/ 4 0 )和 5 5 % (2 2 / 4 0 ) ,阳性检出率与良性病变差异有显著性 ,与肿瘤的分期分级无显著相关性。发生微卫星改变的 33例中 ,33% (11/ 33)和 4 2 % (14 / 33)分别可见 TGF- β 型受体基因和 BAX基因的移码突变。结论　检测染色体微卫星的改变是 BTCC早期诊断、监测复发的有效手段 ,染色体微卫星改变可能是 BTCC发生过程中多基因突变的一种表现形式

Microsatellite change in bladder transitional cell carcinoma and its mechanism

Objective To study the expression of microsatellite change in bladder transitional cell carcinoma(BTCC) and its relationship with gene mutation.Methods Tumor samples from 40 patients with BTCC were analyzed for microsatellite change by PCR. The same way was used to check the mutations of BAX gene and TGF-βⅡ gene in BTCC.Results In 33 of 40 BTCC patients (82%) loss of heterozygosity(LOH) or microsatellite instability(MSI) were found on at least one microsatellite locus.The positive rate of D9S162,D16S476,D9S54,FGA and IFN-A1 was 58%(23/40),42%(17/40),38% (15/40),48%(19/40) and 55%(22/40) respectively, which was higher than of the benign diseases. However,it had no relationship with staging and grading of BTCC. Frameshift mutation of BAX gene and TGF-βⅡ gene was found in 14 and 11 of the 33 cases with microsatellite change respectively,but it was not found in microsatellite change-negative BTCC and control tissue.Conclusion It is an efficient way to diagnose BTCC early and supervise its recurrence through detecting the microsatellite changes.Chromosomal microsatellite change may be a manifestation pattern of polygenic mutation in the BTCC genesis.