荧光原位杂交技术检测膀胱尿路上皮癌尿液的临床应用研究

Clinical Research of FISH Assay in Voided Urine Specimens for the Detection of Bladder Carcinoma

目的:评价荧光原位杂交技术(fluorescence in situ hybridization,FISH)检测膀胱尿路上皮癌患者尿液的应用价值。方法:收集我院2007年10月～2009年4月期间77例膀胱尿路上皮癌患者、43例非尿路上皮癌的血尿患者(通过膀胱镜检查排除尿路上皮癌)和泌尿系良性疾病患者的晨尿,同时行FISH检测和尿脱落细胞学分析,再结合病理结果将两种方法进行比较。FISH检测使用荧光标记DNA探针混合物与细胞核上3、7、17号染色体着丝粒和9p16位点进行杂交。结果:FISH总的敏感度和特异度分别为89.6%和95.3%,G_(1～3)各级的敏感度分别为76.1%、90.9%、100%,Ta、T_(is)、T_1、T_(2～4)各期的敏感度分别为55.6%、100%、88.9%、97.4%。尿脱落细胞学分析总的敏感度和特异度分别为37.7%和93.0%,G_(1～3)各级的敏感度分别为0%、33.3%、78.3%,Ta、T_(is)、T_1、T_(2～4)各期的敏感度分别为11.1%、100%、14.8%、56.4%。结论:FISH比尿脱落细胞学提高了膀胱癌患者检测的敏感度,而特异度两者相近。FISH使低级别浅表型膀胱癌的准确率明显提高,几乎能检测出所有高级别的浸润型膀胱癌。相对于尿脱落细胞学,FISH检测更佳。

Objective：To evaluate the clinical value of FISH （Fluorescence in Situ Hybridization） assay in voided urine specimens for detection of bladder carcinoma. Methods： From October 2007--April 2009, morning voiding urine of 77 patients with bladder carcinoma and 43 patients with non-urotbelium carcinoma （excluded the possibility of urothelial carcinoma by cystoscopy）, and urologic nonmalignant diseases were obtained for urine cytology and FISH analysis, comparing the pathological results with the cytological and FISH findings. FISH assay was performed using a mixture of fluorescent labeled DNA probes for the centromeric regions of chromosomes 3, 7 and 17, and the 9p16 region. Results：The overall and specificity for FISH were 89.6% and 95.3%, the sensitivity Tis being 76.1% for G1, 90.9% for G2, 100% for G3, and 55.6% for Ta,100% for Tis,88.9% for T1 ,97.4% for T2-4, respectively. The overall and specificity for urinary cytology were 37.7 % and 93.0 %. The sensitiviTis being 0% for G1, 33.3% for G2, 78.3% for G3, and 11.1% for Ta, 100% for Tis, 14.8% for T1, 56.4% for T2-4. Conclusions： FISH improves the sensitivity rates obtained with urine cytology for bladder cancer, and offers similar specificity, and improves accuracy of detection for low grade-stage and superficial badder cancers, and detects all high grade-stage and infiltrating bladder cancers. FISH is better in detecting urine cast-off than cytology.