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目的分析候选抑癌基因FHIT及其蛋白表达在中国人膀胱移行细胞癌(transitionalcellcarcinoma,TCC)中的异常改变,探讨其潜在的临床意义。方法选取两个位于FHIT基因第5内含子的微卫星多态标记,对40例膀胱TCC患者的肿瘤组织和尿沉渣DNA进行杂合性缺失(lossofheterozygosity,LOH)分析,同时对相应的组织病理切片进行FHIT蛋白的免疫组化染色。结果在40例膀胱TCC患者的肿瘤组织中,两个微卫星多态标记D3S1234和D3S1300中至少有一个发生LOH的频率为57.8%;而在相应的尿沉渣DNA中,这两个位点中至少有一个发生LOH的频率为55.8%。同时在62.5%(2540)的膀胱TCC肿瘤组织检出FHIT蛋白表达缺失;而在FHIT蛋白表达缺失的25例肿瘤组织中,有20例存在一个或两个上述微卫星位点的LOH。结论FHIT基因在膀胱TCC患者的肿瘤组织和尿沉渣DNA中存在高频率LOH,提示这一基因在膀胱TCC的发生发展中可能起重要作用;杂合性缺失可能是膀胱TCC中FHIT蛋白表达下调的重要机理之一。而尿沉渣DNA中FHIT基因的LOH则有可能成为膀胱TCC早期诊断的潜在分子标志之一。
Objective To analyze the abnormal changes of candidate tumor suppressor gene FHIT and its protein expression in Chinese patients with transitional cell carcinoma (TCC) and to explore its potential clinical significance. Methods Two microsatellite markers were located in the fifth intron of FHIT gene, and the loss of heteozygosity (LOH) of tumor tissue and urinary sediment DNA in 40 patients with bladder TCC was analyzed. The corresponding histopathology FHIT protein immunohistochemical staining. Results The frequency of LOH was 57.8% in at least one of the two microsatellite polymorphism markers D3S1234 and D3S1300 in the tumor tissues of 40 patients with bladder TCC. In the corresponding urine sediment DNA, at least one of these two sites One occurrence of LOH occurred at a frequency of 55.8%. Meanwhile, the expression of FHIT protein was detected in 62.5% (2540) of bladder TCC tumor tissues, while in 25 tumor tissues lacking FHIT protein expression, there were 20 cases of LOH with one or two microsatellite loci. Conclusions FHIT gene has high frequency of LOH in bladder cancer TCC and urinary sediment DNA, suggesting that this gene may play an important role in the occurrence and development of bladder TCC. The loss of heterozygosity may be the down-regulation of FHIT protein expression in bladder TCC One of the important mechanisms. Urine sediment DNA FHIT gene LOH may be one of the potential molecular markers of bladder TCC early diagnosis.