荧光原位杂交技术在血尿待诊病因诊断中的临床应用分析

Clinical application of fluoresence in situ hybridization in the etiological diagnosis of hematuria

目的：评价非侵袭性尿脱落细胞学和荧光原位杂交技术（fluorescence in situ hybridzation,FISH）在血尿待诊病因诊断中的应用价值,为建立和完善血尿待诊病因诊断提供理论依据。方法：选取2011年8月~2013年12月因血尿体检的正常人10例,通过FISH技术检测9号染色体p16号位点、3号染色体、7号染色体、17号染色体,建立FISH检测方法并确立阈值。同时收集185例血尿患者晨尿同步进行尿脱落细胞学分析及FISH检测。以病理诊断尿路上皮癌为金标准,评估FISH诊断的特异性和敏感性及与膀胱癌发生和发展的关系。结果：FISH检测尿路上皮癌患者的特异性为91.8%,敏感度为94.3%;尿脱落细胞学诊断的特异性为97.3%,敏感性为36.1%。两者相比,敏感性差异有统计学意义（P〈0.05）,而特异性差异无统计学意义。结论：与尿脱落细胞学相比,FISH在血尿病因学膀胱癌患者的诊断中具有较高灵敏度,而特异度两者相近。FISH使低级别浅表型尿路上皮癌的准确率明显提高,几乎能检测出所有高级别的浸润性膀胱癌。FISH的染色体3、7、9和17是血尿恶性疾病鉴别诊断尿路上皮癌的一种有前途、无创性分子检测方法。

Objective：To evaluate the clinical value of cytological examination and fluorescence in situ hybrid- ization （FISH） as non-invasive molecular tests in the etiological diagnosis of hematuria so as to provide the theo- retical basis for establishing and improving the diagnosis of malignant hematuria. Method：Labeled probes for chro- mosomes 3, 7, 17 and 9 （p16） were used to assess chromosomal abnormalities by FISH from ten people without hematuria and established the threshold from August 2011 to December 2013, and the other 185 urine samples from people with hematuria were analyzed by FISH and cytology at the same time. The specificity and sensitivity of FISH and its relationship with carcinogenesis and tumor progression of bladder cancer were evaluated. Result： The specificity of FISH and cytology in detecting urothelial cancer （UC） were 91.8% and 97.3% respectively, and the sensitivity were 94.3 % and 36.1% respectively. There is a significant difference between the sensitivity of FISH and cytology （P〈0.05）, but no significant difference was found in specificity between two methods. Con- clusion：Compared with cytological examination, FISH assay has a higher sensitivity and a similar specificity in the detection of bladder cancer. FISH significantly increases the accurate rate of low grade superficial UC, and can de- tect almost all the high level of invasive bladder cancer. FISH of chromosomes 3, 7, 9 and 17 may be a promising non-invasive molecular test in the differential diagnosis of UC from benign diseases with hematuria.