芳香胺暴露相关性膀胱癌微卫星改变的初步研究

Abnormalities of microsatellite in transitional cell carcinoma of urinary bladder related with aromatic amine exposure

目的分析芳香胺暴露相关性膀胱移行细胞癌(TCC)与散发性膀胱TCC微卫星异常改变的特点,探讨微卫星分析在职业性膀胱TCC诊断中的潜在应用价值。方法选择在散发性膀胱TCC中杂合性缺失(LOH)频率较高的5个微卫星位点(D17S695、D9S162、D3S1295、DBH及D3S1234),盲法检测这5个位点在16例芳香胺暴露相关性膀胱疾病患者病变组织中的LOH频率,比较其组合LOH缺失模式与病理诊断的符合率,检测患者术后尿沉渣中这5个微卫星位点的改变情况。结果16例职业性膀胱疾病患者的DNA在被测的5个位点中至少有1个位点存在多态性;14例膀胱TCC组织中这5个位点中至少有1个发生LOH的频率达62.50%(10/16)。与散发性膀胱TCC相比,D3S1295的LOH频率增高;被检膀胱病变组织DNA至少1个位点发生LOH的病例,与其组织病理学诊断的符合率达81.25%(13/16)。在8例膀胱TCC患者术后尿沉渣中亦发现了至少1个位点的LOH。结论职业暴露相关性膀胱TCC可能存在不同于散发性膀胱TCC的微卫星LOH模式;D3S1295附近可能存在与芳香胺暴露性膀胱TCC发生相关的基因。

Objective To study the mierosatellite abnormalities of the aromatic amine exposure-associated transitional cell eareinoma（TCC）and sporadic TCC of urinary bladder,and to evaluate the potential of mierosatellite analysis on detection of this diseases. Methods Based on our previous investigations, 5 mierosatellite markers （D17S695, D9S162, D3S1295,DBH and D3S1234） that had high frequencies of loss of heterozygosity（LOH） in sporadic TCC, were selected for analysis with the bladder lesions derived from 16 patients with aromatic amine exposure history. The mierosatellite analysis with urine sediments from the post-operated patients was also carried out. Results There was at least one informative marker out of the 5 mierosatellite loci showed polymorphism in the DNA derived from 16 patients examined. Within 62.50% （10/16） patients, LOH was detected in the bladder lesions at least with one mierosatellite marker. The LOH frequency of D3S1295 was higher in oceupatonal TCC patients than that in sporadic TCC patients. The diagnostic accordance rote of patients showed LOH in at least one mierosatellite marker with patients diagnosed by pathology was 81 . 25 % （13/16）. In the urine sediments from 8 TCC post-operated patients, LOH was found at least with one mierosatellite marker. Conclusion There could be a different LOH pattern in aromatic amine exposure-associated TCC,and genes near D3S1295 might play a role in the occupational exposure-associated TCC.