荧光原位杂交法在膀胱尿路上皮癌诊断中的应用

目的：探讨荧光原位杂交法（FISH）在膀胱尿路上皮癌诊断中的应用。方法：选取20例非尿路上皮癌和40例膀胱尿路上皮癌的人群尿液作常规尿脱落细胞学检查和FISH检测。结果：FISH技术的敏感性为82．5％,显著高于常规尿脱落细胞学的敏感性25．0％（P〈0．05）;FISH技术和常规脱落尿细胞学检查的特异性均为100％,两者在特异性方面差异无统计学意义（P〉0．05）。结论：荧光原位杂交法在膀胱尿路上皮癌诊断中的特异性与常规尿脱落细胞学检查一致,但其敏感性显著高于常规尿脱落细胞学检查,所以,FISH技术更有望成为膀胱尿路上皮癌无创性的诊断和检测手段。     

荧光原位杂交技术在膀胱尿路上皮癌诊断中的应用价值

目的 探讨荧光原位杂交技术(fluorescence in situ hybridization,FISH)在膀胱尿路上皮癌诊断中的应用价值. 方法 收集81例膀胱尿路上皮癌患者的新鲜尿液标本,分别行FISH和尿细胞学检测,并行膀胱镜检查;病理诊断泌尿系良性疾病12例合并8例临床诊断泌尿系良性疾病患者的尿液标本作对照.统计学分析FISH和尿细胞学检测诊断的特征值. 结果 81例均经病理检查确诊膀胱尿路上皮癌.非肌层浸润性膀胱尿路上皮癌34例,肌层浸润性癌14例;低级别42例,高级别24例;由于送检组织不完整,无法准确分期、分级者分别为33例和15例.FISH、尿细胞学和膀胱镜检查诊断膀胱尿路上皮癌的敏感性分别为72.8％ (59/81) 、27.2％ (22/81)和97.5％ (79/81),FISH诊断敏感性高于尿细胞学检测(P＜0.05),但低于膀胱镜检查(P ＜0.05);FISH和尿细胞学检测诊断特异性分别为85.0％(17/20)、100.0％ (20/20),二者比较差异无统计学意义(P＞0.05).FISH和尿细胞学检测诊断符合率分别为75.2％ (76/101)、41.6％(42/101),二者比较差异有统计学意义(P＜0.05). 结论 FISH检测诊断膀胱尿路上皮癌敏感性高、特异性强、无创,临床应用价值高.     

荧光原位杂交在膀胱尿路上皮癌诊断中的应用

目的评价尿脱落细胞荧光原位交(fluorescenceinsituhybridization,FISH)检测在膀胱肿瘤诊断中的应用价值。方法分别对69例疑似膀胱尿路上皮癌及20例对照组的尿液标本进行FISH及细胞学检测,比较两者诊断的敏感性及特异性,统计膀胱尿路上皮癌各个染色体畸变的几率。结果 FISH诊断膀胱尿路上皮癌的总的敏感度高于尿脱落细胞学检查(分别为79.7%、22.0%,P<0.05),两者的特异度分别为93.3%、100%(P>0.05)。结论 FISH在诊断膀胱尿路上皮癌中敏感性高于尿细胞学检查,同时其特异性亦较高,在早期诊断中具有重要意义。     

荧光原位杂交技术在膀胱尿路上皮癌诊断中的临床应用

目的 探讨荧光原位杂交(FISH)技术运用于膀胱尿路上皮癌的诊断价值.方法 收集20例健康志愿者的新鲜晨尿,运用荧光标记的3号、7号、17号染色体着丝粒探针及9号染色体p16位点探针,对尿液标本中的脱落细胞染色体进行FISH技术检测,建立正常人群的阈值.收集158例怀疑为膀胱尿路上皮癌患者的新鲜晨尿,在行膀胱镜检查前,同期进行FISH技术与尿脱落细胞学检测,运用统计学方法,比较FISH技术与尿脱落细胞学检测的敏感性与特异性.结果 FISH与尿脱落细胞学的敏感性分别为84.8%和43.8%,FISH敏感性高于尿脱落细胞(P<0.05),FISH与尿脱落细胞学特异性分别为89.1%和87.0%,两者无统计学差异(P>0.05),在不同的肿瘤病理分级中,FISH的敏感性都高于尿脱落细胞,并且FISH敏感性随肿瘤分级逐级升高(P<0.05).结论 FISH技术具有较高的敏感性和特异性,可以作为国人膀胱尿路上皮癌筛查、诊断的新方法.     

荧光原位杂交技术在膀胱尿路上皮癌中的临床应用研究

目的:本研究旨在利用荧光原位杂交技术(FISH)辅助诊断膀胱尿路上皮癌,以探讨其作为一种替代尿脱落细胞学的无创性检查在膀胱尿路上皮癌诊断中的应用价值。方法:收集30例健康志愿者的新鲜尿液,应用3、7、17号染色体及9号染色体p16位点探针标记,进行FISH检测,建立正常人群阈值;再收集95例因血尿或影像学检查拟诊为膀胱肿瘤的患者晨尿标本,分别作常规尿脱落细胞学检查和FISH检测,其中79例膀胱镜下活检或术后标本病理确诊为膀胱尿路上皮癌。FISH检测统计目标染色体畸变情况,并进一步分析与病理分级的关系。结果:FISH检测设定的正常阈值为3号染色体:3%;7号染色体:4%;17号染色体:3%;9号染色体p16位点:10%。FISH检测技术的敏感性为74.68%(59/79),高于尿脱落细胞学检查的35.44%(28/79),差异具有统计学意义(P>0.001),而FISH检测的特异性为93.75%(15/16),尿脱落细胞学检查特异性为87.50%(14/16),两者差异无统计学意义(P>0.05)。不同病理分级下FISH检测的敏感性呈现为高级别高阳性率:低度恶性倾向的尿路上皮肿瘤为58.33%(7/12),尿路上皮癌Ⅰ级为54.17%(13/24),尿路上皮癌Ⅰ～Ⅱ级为86.36%(19/22),尿路上皮癌Ⅱ级和Ⅱ～Ⅲ级为94.44%(17/18),尿路上皮癌Ⅲ级为100%(3/3),敏感性随着病理分级的提高而呈现增高趋势。结论:FISH检测技术具备无创、高敏感性的特点,优于传统的尿脱落细胞学检查。不同分级的膀胱尿路上皮肿瘤其FISH检测的敏感性不同,表现为高级别高敏感性。FISH检测上述位点在低级别膀胱尿路上皮肿瘤中敏感性较高,大大提高了低级别尿路上皮肿瘤的检出率,有望成为一种常规的膀胱肿瘤复查指标。     

荧光原位杂交在非肌层浸润行膀胱尿路上皮癌术后随访中的应用

目的:研究多色荧光原位杂交探针(FISH)在非肌层浸润性膀胱尿路上皮癌术后监洲的应用价值,并与尿细胞学检查相比较.方法:应用FISH和尿细胞学检查分析215例非肌层浸润性膀胱尿路上皮癌术后随访尿沉渣标本.FISH探针是用随机引物法标记3、7、17号染色体着丝粒及9p21区带.比较分析两种检查结果.结果:215例中有58例患者病理证实膀胱尿路上皮癌复发.FISH对膀胱尿路上皮癌诊断高于尿脱落细胞学检查(71.4%和26.2 %),并有统计学差异(P<0.05),特异性分别为90%和95%,无统计学差异;阳性预测值分别是95.5%和95.7%,阴性预测值分别为52.9%和34.5%.结论:FISH检查可以作为非肌层浸润性尿路上皮癌术后随访的手段,并且敏感性高于尿细胞学检查.     

荧光原位杂交技术在尿路上皮癌诊断中的应用

目的 探讨荧光原位杂交技术( FISH)在尿路上皮癌诊断中的应用价值.方法 采用FISH检测100例血尿患者尿脱落细胞中第3、7、17号染色体和第9号染色体p16位点异常,以组织病理学确诊尿路上皮癌为金标准,评估FISH诊断的敏感度和特异度,并与尿细胞学检查结果进行比较.结果 FISH检测和尿细胞学检查诊断尿路上皮癌的敏感度分别为82.5％和49.2％, 差异有统计学意义(P＜0.05)；特异度分别为86.7％和96.6％,差异无统计学意义(P＞0.05).结论 与尿细胞学比较,FISH诊断尿路上皮癌具有较高的敏感度和相似的特异度.     

血尿的病因分析及荧光原位杂交技术用于诊断尿路上皮癌的价值

目的总结并分析初发血尿的病因,同时比较荧光原位杂交技术(FISH)与尿脱落细胞学检查技术在诊断尿路上皮癌(UC)中的敏感性和特异性,从而进一步评估FISH用于筛查尿路上皮癌的临床价值。方法回顾性分析500例入院诊断为"血尿待查"患者的最终出院诊断结果,同时记录其中每例患者的检查诊治经过。计算比较FISH与尿脱落细胞学检查的敏感性与特异性。结果 500例初次诊断血尿待查患者中最终诊断为尿路上皮癌130例、泌尿系结石30例、泌尿系感染135例、前列腺癌12例、前列腺增生(BPH)相关出血66例、乳糜血尿23例、特发性血尿60例、其他44例。有218例诊疗过程中同时采用了FISH检测和尿脱落细胞学检查;FISH敏感性明显优于脱落细胞学(75.4%vs.33.9%,P0.001),两者特异性无明显差异(96%vs.99%,P=0.837)。对于上尿路尿路上皮癌(UTUC)的诊断,FISH和尿脱落细胞学检查敏感性分别为80.4%和34.8%(P0.001)。结论血尿待查病因复杂多样,需要临床医生扎实的基础和临床理论知识及正确的临床思维能力。FISH对于尿路上皮癌尤其是上尿路尿路上皮癌的诊断具有重要价值。     

荧光原位杂交(FISH)技术在尿路上皮癌诊断中的应用研究

目的探讨荧光原位杂交(fluorescence in situ hybridization,FISH)技术在尿路上皮肿瘤诊断中的价值。方法以89例血尿待查患者作为研究对象,分别进行尿脱落细胞学检查和FISH检测,并对其结果进行分析和对比。结果尿脱落细胞学检查和FISH检测对于诊断尿路上皮肿瘤的总敏感性分别为52.2%和89.6%(P<0.05),特异性分别为95.5%和90.9%(P=0.546),诊断符合率分别为62.9%和89.9%(P<0.05)。两种检测方法在尿路上皮肿瘤的诊断总敏感性和诊断符合率方面的差异均具有统计学意义;而在特异性方面的差异则无统计学意义。结论对于尿路上皮癌的检测,FISH检测的敏感性明显高于尿脱落细胞学检查,而两者特异性的差异不具统计学意义。FISH技术是一种尿路上皮癌早期诊断及术后监测的新方法。     

荧光原位杂交(FISH)技术对尿路上皮癌诊断价值的Meta分析

目的对国内已发表的应用荧光原位杂交(FISH)技术对尿路上皮癌患者的临床试验进行综合评价,对FISH技术与传统尿脱落细胞学检查进行比较,评价其对尿路上皮癌的诊断价值方法检索相关文献,根据纳入标准筛选文献,利用Meta-DiSc软件分别计算FISH检测组和尿脱落细胞学检查组敏感性、特异性、似然比和诊断性比数比,绘制总受试者工作特征(SROC)曲线,计算曲线下面积,并比较。结果有8篇文献被纳入,FISH检测尿路上皮癌的总敏感性为0.83(95%CI 0.79～0.86),特异性为0.90(95%CI 0.85～0.93),SROC曲线下面积为0.9278。尿脱落细胞学检查的总敏感性为0.51(95%CI0.47～0.56),特异性为0.93(95%CI 0.90～0.96),SROC曲线下面积为0.8501。FISH检查在总体诊断效能上较尿脱落细胞学检查更高,且具有统计学意义(P0.05)。结论就本次Meta分析的结果而言,可以认为FISH检测较尿脱落细胞学检查在尿路上皮癌的诊断中具有更高的价值。     

荧光原位杂交技术在膀胱尿路上皮癌诊断中的应用价值

目的:评估荧光原位杂交技术(FISH)在膀胱尿路上皮癌诊断中的应用价值。方法:收集60例疑似膀胱癌的血尿患者的尿液标本,分别作尿细胞学检测和荧光原位杂交分析。20例正常人尿液标本,用于建立FISH阀值,作为阳性判断的标准。结果:细胞学和FISH的总敏感性分别为42.0%、82.2%,特异性分别为:93.3%、86.7%。细胞学和FISH在低级别及非肌层浸润性肿瘤等敏感性的均差异有统计学意义(P<0.05)。结论:FISH技术能明显提高膀胱尿路上皮癌的检出率,尤其是早期和低级别病变,可以成为筛查膀胱尿路上皮癌的一种新的无创性检查方法。     

A comparative study of the sensitivity of bladder washing flow cytometry, voided urine cytology and bladder washing cytology in the detection of bladder carcinoma

In order to evaluate flow cytometric deoxyribonucleic acid measurement (FCM) of bladder washing in the diagnosis of bladder carcinoma, the sensitivity of voided urine cytology, bladder washing cytology and bladder washing FCM was tested in 76 samples from 56 patients with histologically proven bladder carcinomas. The positive rates were 43.2% and 75.7% in bladder washing cytology and bladder washing FCM, respectively. On the other hand, 36.5% and 57.1% positive rates for once- and three-times-voided urine cytology, respectively, were obtained. Bladder washing cytology and bladder washing FCM were positive in 20% and 70% patients with a histological diagnosis of atypia or dysplasia, respectively. The sensitivity of bladder washing FCM according to the tumor grade was 33.3%, 81.9% and 88.9% for grade-1 (G-1), G-2 and G-3 tumors, respectively. The sensitivity of bladder washing cytology according to the tumor grade was 0, 40.9% and 77.8% for G-1, G-2 and G-3 tumors, respectively. The sensitivity of three-times-voided urine cytology was 25.0%, 55.6% and 83.3% for G-1, G-2 and G-3 bladder tumors, respectively, and it was superior to that of single bladder washing cytology. These results indicate that FCM is more sensitive than voided urine cytology and/or bladder washing cytology in patients with bladder carcinoma. FCM may indicate urothelial neoplasia before it is apparent on urine cytology, especially against a background of inflammation. Therefore, FCM is valuable for case finding in suspect populations or for follow-up cases with diagnosed bladder cancer.     

A comparison of cytology and fluorescence in situ hybridization for the detection of urothelial carcinoma

PURPOSE: We determine the relative sensitivities of cytology and fluorescence in situ hybridization (FISH) for the detection of urothelial carcinoma. MATERIALS AND METHODS: A mixture of fluorescent labeled probes to the centromeres of chromosomes 3, 7 and 17, and band 9p21 (P16/CDKN2A gene) was used to assess urinary cells for chromosomal abnormalities indicative of malignancy. A total of 280 urine specimens from 265 patients, including 150 with a history of urothelial carcinoma and 115 without a history of urothelial carcinoma, were analyzed. FISH analysis was performed without prior knowledge of clinical findings, that is biopsy, cystoscopy and cytology results. A positive result was defined as 5 or more urinary cells with gains of 2 or more chromosomes. RESULTS: A total of 75 biopsies showed urothelial carcinoma at FISH analysis among the 265 patients. The sensitivity of urine cytology for pTa (36 cases), pTis (18) and pT1-pT4 (15) tumors was 47%, 78% and 60%, respectively, for an overall sensitivity of 58%. The sensitivity of FISH for pTa (37 cases), pTis (17) and pT1-pT4 (19) tumors was 65%, 100% and 95%, respectively, for an overall sensitivity of 81%. FISH was significantly more sensitive than cytology for pTis (p = 0.046), pT1-pT4 (p = 0.025), grade 3 (p = 0.003) and all tumors (p = 0.001). The specificity of cytology and FISH among patients without cystoscopic evidence of urothelial carcinoma and no history of urothelial carcinoma was 98% and 96%, respectively (p = 0.564). CONCLUSIONS: The sensitivity of FISH for the detection of urothelial carcinoma is superior to that of cytology, and the specificity of FISH and cytology for urothelial carcinoma are not significantly different. Further prospective studies are required but FISH has the potential to improve significantly the management of urothelial carcinoma.     

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

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％,G1-3各级的敏感度分别为76．1％、90．9％、100％,Ta、Tis、T1、T2-4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％,G1-3各级的敏感度分别为0％、33．3％、78．3％,Ta、Tis、T1、T2-4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。     

Study on the diagnosis of urothelial cancer using multi-colour fluorescence in situ hybridization (FISH)--comparative analysis between FISH and cytology

To determine the diagnostic merit or demerit of genetic procedures using fluorescence in situ hybridization (FISH) for detecting both new and recurrent urothelial cancer, we analyzed the specimens from 81 out-patients with asymptomatic haematuria, aged over 40, in comparison with urine cytology. Of 10 with atypical cytology, 6 showed positive for FISH, and of these, 4 manifested urothelial cancer. FISH showed higher sensitivity in low/intermediate grade cases compared with cytology (FISH; 66.7% vs cytology; 11.1%). Of 15 primary bladder cancer, 4 showed recurrence, and all of these cases showed a positive FISH reaction, but only 1 in cytology. The sensitivity, specificity and accuracy of FISH tests were 81.2, 72.3 and 74.1%, respectively, and these of cytology were 37.5, 98.5 and 86.4% respectively. The FISH test was superior to cytology for sensitivity, but specificity and accuracy were inferior. The FISH tests could be a potent procedure for detecting urothelial cancer in cases of low/intermediate grade, atypical cytology and surveillance setting.     

自噬相关基因 LC3、Beclin-1与凋亡相关基因BCL-2在膀胱尿路上皮癌中的表达

目的 检测自噬相关基因LC3、Beclin-1与凋亡相关基因BCL-2在膀胱尿路上皮癌和膀胱正常组织中的表达情况,探讨其与膀胱尿路上皮癌发生、发展的相关性。 方法 应用免疫组化SP法检测10例正常膀胱组织及56例膀胱尿路上皮癌组织中LC3、Beclin-1及BCL-2 蛋白的表达水平,并结合临床病理因素进行分析。结果 LC3在膀胱癌的阳性表达率高于正常膀胱组织( P＜0. 05),且与膀胱尿路上皮癌的组织学分化程度及肿瘤分期相关( P ＜0. 05)。Beclin-1在膀胱尿路上皮癌组织中的表达高于正常膀胱组织( P ＜0. 05),且与膀胱尿路上皮癌的组织学分化程度相关（P＜0.01）。BCL-2在膀胱癌组织中的表达显著高于正常膀胱组织( P＜0. 01),且与膀胱尿路上皮癌淋巴结转移相关( P＜0. 05)。经Spearman秩相关检验,LC3蛋白、Beclin-1蛋白的表达均与BCL-2蛋白的表达呈正相关,相关系数分别为0.3436（P＜0. 05)和0.3593（P＜0. 01)。结论 在膀胱尿路上皮癌中,自噬活性的上调与凋亡能力的下调并存,自噬相关基因LC3、Beclin-1与凋亡相关基因BCL-2在膀胱尿路上皮癌的发生、发展中起协调作用,对其联合检测有助于判断膀胱尿路上皮癌的进展程度及患者的预后情况。     

荧光原位杂交技术在尿路上皮癌预警诊断中的应用

目的：探讨使用荧光原位杂交技术对尿路上皮癌进行预警诊断的可行性和有效性。方法：采用3、7、17号染色体着丝粒探针和9p21区带探针对30例影像学检查、膀胱镜检查、尿脱落细胞学检查均为阴性的高度可疑的尿路上皮癌的血尿患者尿液脱落细胞核行荧光原位杂交检测。结果：30例血尿患者中,11例FISH结果阳性。随访3～13个月。有5例确诊为膀胱尿路上皮癌,2例确诊为肾盂癌。19例FISH检测阴性的患者无一例患病。结论：尿脱落细胞荧光原位杂交技术对膀胱镜和尿脱落细胞学检查阴性的早期尿路上皮癌患者有预警诊断作用．具有重要的临床应用价值。