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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 analyze the characteristics of microsatellite anomalous changes in bladder transitional cell carcinoma (TCC) and sporadic bladder cancer (TCC) associated with aromatic amine exposure and to explore the potential value of microsatellite analysis in the diagnosis of bladder cancer. Methods Five microsatellite loci (D17S695, D9S162, D3S1295, DBH and D3S1234) with high loss of heterozygosity (LOH) in sporadic bladder TCC were selected. Six of the six aromatic amine The frequencies of LOH in the diseased tissues of patients with related bladder diseases were compared, and the coincidence rates of LOH pattern and pathological diagnosis were compared to detect the changes of these 5 microsatellite loci in postoperative urinary sediments. Results The DNA of 16 patients with occupational bladder disease had polymorphism in at least one of the 5 loci tested. The frequency of LOH occurred in at least 1 of the 5 bladder TCC tissues Up to 62.50% (10/16). Compared with the sporadic bladder TCC, the LOH frequency of D3S1295 was increased. The incidence of LOH in at least one locus of bladder cancer tissue was 81.25% (13/16) in accordance with the histopathological diagnosis. At least one site of LOH was also found in postoperative urinary sediment in 8 patients with bladder TCC. Conclusions Occupational exposure-associated bladder TCC may have microsatellite LOH pattern different from that of sporadic bladder TCC. Genes related to the development of bladder cancer TCC may be present near D3S1295.