荧光原位杂交技术在血尿患者膀胱尿路上皮癌筛查中的应用

Detection of bladder cancer from the urine using fluorescence in situ hybridization(FISH)technique

目的评价荧光原位杂交(fluorescence in situ hybridization,FISH)技术在血尿患者膀胱尿路上皮癌筛查中的临床应用价值,为从尿液脱落细胞中早期诊断膀胱癌提供新的途径。方法选择20例健康正常人,通过FISH技术检测9号染色体p16位点、3号染色体、7号染色体及17号染色体变异情况,建立阈值。100例血尿患者留取晨尿,分别进行尿脱落细胞学检查和FISH技术检查。统计分析FISH方法的敏感度和特异度。结果探针检测p16基因完全缺失阈值为3.9%,部分缺失为5.4%,扩增为3.2%;3号染色体缺失阈值为4.0%,扩增为3.5%;7号染色体缺失阈值为4.0%,扩增为2.8%;17号染色体缺失阈值为5.8%,扩增为3.4%。以至少两种探针检测结果超过阈值或一种探针检测结果至少存在两种异常为诊断阳性。FISH技术在血尿患者膀胱尿路上皮癌筛查中的敏感度和特异度分别为93.6%和100%,尿脱落细胞学检测分别为46.8%和100%。结论 FISH技术无创快速,对血尿患者膀胱尿路上皮癌筛查的敏感度优于尿脱落细胞学检查方法。

Objective To evaluate the clinical significance of fluorescence in situ hybridization （FISH） technique for screening bladder transitional cell carcinoma with hematuria, provide a new method for early diagnosis of bladder cancer with cytology of the urine. Methods We selected 20 relatively healthy people as control group. The special urine examination method detects genetic al- terations of the urothelial cells found in the urine of the control group, using fluorescent direct la- beled DNA probes binding to the peri-centromeric regions of chromosomes 3, 7 and 17 as well as on the 9p21 locus, respectively. Thresholds were then established. Morning urine samples collecting from 100 patients with hematuria underwent cytology of the urine and FISH examination, respectively. The sensitivity and specificity of both were analyzed statistically. Results The complete absent, the partial absent and amplification thresholds for p16 gene detected by probes were 3.9%, 5. 4% and 3.2%, respectively. The absent and amplification thresholds for chromosome 3 were 4.0% and 3.5 %; 4.0 %and 2.8% for chromosome 7 ; 5.8 %fro and 3.4 %for chromosome 17 respectively. The study rated the specificity and sensitivity of the technique 93.6% and 100%, respectively. The study rated the specificity and sensitivity of the urinary exfoliative cytology 46.8% and 100%, respectively. Conclusions This new non-invasive diagnostic application of the FISH technique with high detection rate in the field of urology is prior to urinary cytology.