荧光原位杂交检测尿路上皮癌分子细胞遗传学变异的临床应用研究*

目的:探讨荧光原位杂交（fluorescence in situ hybridization,FISH）在检测尿路上皮癌患者尿液中脱落细胞核染色体畸变的临床应用价值。方法:采用3 号、7 号及17号染色体着丝粒特异性探针及p16位点特异性DNA探针对20例正常人尿液进行FISH检测,建立阈值。对115 例疑似尿路上皮肿瘤血尿患者的尿液进行FISH检测,以至少两种探针检测结果超过阈值或一种探针检测结果存在至少两种异常为诊断阳性。同时采用常规HE染色法进行尿脱落细胞形态学分析。结果:荧光原位杂交（FISH）技术和尿脱落细胞学诊断尿路上皮癌的灵敏度分别为86.7%（78/90）和10.0%（9/90）（P<0.001）;特异度分别为96.0%（24/25）和100%（25/25）（P>0.05）;阳性预测值分别为98.7%（78/79）和100%（9/9）（P>0.05）;阴性预测值分别为66.7%（24/36）和23.6%（25/106）（P<0.05）。 FISH技术诊断尿路上皮癌的灵敏度与尿路上皮癌的病理分级及分期无关,低级别和高级别尿路上皮癌FISH技术诊断的阳性率分别为85.7% 和87.5%（P>0.05）;非肌层浸润性和肌层浸润性尿路上皮癌的阳性率分别为84.2% 和88.4%（P>0.05）。 结论:尿脱落细胞荧光原位杂交技术诊断尿路上皮癌灵敏度高,特异度强,无创伤性,可作为尿路上皮癌早期诊断的一项重要方法,并可在预测肿瘤生物学行为及预后关系上具有重要的临床意义。      

荧光原位杂交在尿路上皮癌诊断中的应用

目的:检测尿路上皮肿瘤患者尿液脱落细胞染色体的缺失和非整倍异常,探讨FISH技术作为尿路上皮肿瘤患者无创诊断方法的价值.方法:收集可疑尿路上皮肿瘤患者和健康对照人群的新鲜尿液,同步进行细胞形态学分析及荧光原位杂交(Fluorescencein situ hybridization,FISH)检测3号、7号及17号染色体、9号染色体p16位点异常.共入选可疑尿路上皮肿瘤患者100例,正常健康对照组20例,采用正常对照组患者各染色体异常数据设定阈值用于肿瘤患者的实验室诊断.根据检验结果与病理结果对照分别计算FISH和脱落细胞的敏感度和特异度并进行统计学分析.结果:与正常对照组相比,尿路上皮肿瘤患者尿液脱落细胞染色体异常明显增多.尿脱落细胞学的敏感度和特异度分别为71%和80%,FISH的敏感度和特异度分别为88%和80%(P<0.01).根据两种检测方法的敏感度和特异度绘制的接受者工作特征(ROC)曲线显示尿脱落细胞学和FISH的曲线下面积分别为0.758和0.842.结论:对可疑尿路上皮肿瘤的患者进行FISH检测是一种有价值的无创检测方法.FISH的总体敏感度高于尿脱落细胞学,特异度与尿脱落细胞学相当.     

荧光原位杂交在膀胱尿路上皮癌中的应用

目的探讨3,7,17号染色体及9p21(p16基因)组合探针在监测膀胱尿路上皮癌术后复发及诊断膀胱尿路上皮癌的应用价值。方法利用荧光原位杂交（FISH）检测膀胱尿路上皮癌患者的尿脱落细胞及组织切片中3,7,17号染色体及9p21组合的畸变情况。结果FISH监测膀胱尿路上皮癌术后复发的敏感度为87.50%;术前FISH阳性的患者术后更易复发;FISH诊断膀胱尿路上皮癌的阳性率为78.85％。结论利用FISH检测尿脱落细胞中3,7,17号染色体及9p21组合的畸变能有效辅助监测膀胱尿路上皮癌术后复发;并可能在一定程度上预测术后复发;同时利用FISH检测组织切片中3,7,17号染色体及9p21组合的畸变也能有效辅助膀胱尿路上皮癌的诊断。     

荧光原位杂交技术在膀胱尿路上皮肿瘤病理学诊断中的初步应用

目的应用荧光原位杂交（fluorescence in situ hybridization,FISH）技术,了解膀胱尿路上皮肿瘤细胞核染色体畸变情况及其对病理诊断及鉴别诊断的应用价值。方法采用3、7、17号染色体着丝粒及p16基因探针,对33例不同级别膀胱尿路上皮肿瘤组织和10例正常对照膀胱组织进行FISH检测。结果 3、7、17染色体及p16扩增率与缺失率,浸润性尿路上皮癌与其他5组比较均有统计学意义（P〈0.01）;而其他各组间比较无统计学意义（P〉0.05）,4种探针联合检测≥2个指标出现异常,浸润性尿路上皮癌占100%,与其他5组比较有统计学意义（P〈0.01）;该指标对浸润性尿路上皮癌诊断敏感性为81.82%、特异性为91.67%。结论应用FISH技术,可以了解膀胱尿路上皮肿瘤组织3、7、17染色体及p16基因的畸变情况,FISH技术还可作为尿路上皮肿瘤病理学诊断与鉴别诊断及术后监测的重要手段。     

RT-PCR法检测尿脱落细胞中XIAP的表达在膀胱癌诊断中的价值

目的：比较膀胱癌患者尿液脱落细胞中XIAP表达的RT-PCR检测法和常规尿脱落细胞病理学检测在膀胱癌诊断中的临床价值。方法：采用逆转录聚合酶链反应技术（RT-PCR）检测51例膀胱尿路上皮癌患者尿液脱落细胞中XIAP-mRNA的表达,同时行常规尿脱落细胞病理学检测,20例非肿瘤人员作为对照组。结果：实验组51例尿脱落细胞XIAP-mRNA RT-PCR检测阳性27例（53%）,尿脱落细胞学病理学检测阳性12例（24%）,对照组20例尿脱落细胞XIAP-mRNA检测阳性1例（5.0%）,对照组尿脱落细胞病理学检测阳性0例（0%）。实验组RT-PCR检测膀胱尿路上皮癌患者尿脱落细胞中XIAP表达的敏感性高于尿脱落细胞病理学检测,差异有极显著统计学意义（P〈0.01）,实验组RT-PCR检测膀胱尿路上皮癌患者尿中XIAP表达的敏感性显著高于非肿瘤对照组,差异有极显著统计学意义（P〈0.01）。结论：膀胱尿路上皮癌患者尿脱落细胞中XIAP表达的RT-PCR检测法较常规尿脱落细胞病理学检测更敏感,临床上作为膀胱癌的筛选方法,有一定的临床价值。     

支气管刷检液基细胞学在肺癌诊断中的应用价值

目的:探讨支气管刷检液基细胞学在肺癌诊断中的应用价值。方法:支气管刷检标本做液基细胞学检测,剩余标本制作成细胞块切片。结果:液基细胞学诊断肺癌的敏感度、特异度、准确度分别为89.5%、94.3%、91.4%,分型诊断准确率为90.4%。细胞块切片诊断肺癌的敏感度、特异度、准确度分别为95.1%、100%、97.4%,分型诊断准确率为84.6%。两组的敏感度、特异度、准确度及分型诊断准确率比较差异均无统计学意义（P>0.05）。结论:液基细胞学诊断肺癌的敏感度、特异度高,大部分肺癌能准确分型,与细胞块切片合用有互补作用,液基细胞学可作为肺癌早期诊断的有效方法。     

尿脱落细胞FISH检测在膀胱癌诊断中的应用

目的:研究尿脱落细胞FISH检测提高膀胱癌早期诊断的可行;方法:收集68例腺膀胱炎患者晨尿通过FISH检测GLP p16、CSP3、CSP17和CSP7染色体异常信号,并用统计学方法计算出阈值.为了验证FISH检测的优越,实验选取临床诊断膀胱癌最常用的尿脱落细胞学检测作为研究对照方法,收集100例疑似膀胱癌患者尿液标本,分别对尿脱落细胞和FISH检查诊断膀胱癌的敏感、特异、FISH检测与膀胱癌临床及病理特征的关系进行统计学分析.结果:100例疑似膀胱癌患者尿脱落细胞及FISH检测的阳率分别为56.0％ (56/100)和77.0％(77/100),敏感度分别为56.10％(46/82)和82.02％(73/89),经统计学分析两种检查方法之间的差异具有统计学意义.FISH检测的敏感和总阳率明显高于尿脱落细胞,而特异两者差异无统计学意义.FISH检测与膀胱癌的病理分级和临床分期均无相关.结论:FISH检测技术是能够成为提高膀胱癌早期诊断的一种新技术.     

痰液细胞DNA定量分析在原发性肺癌中的诊断价值

目的:探讨痰液细胞DNA定量分析技术(DNA-ICM)在原发性肺癌诊断中的临床意义。方法:分别采用细胞DNA-ICM和液基细胞学技术(LBC)对300例可疑肺癌患者痰液进行检查,并将结果进行比较分析。结果:细胞DNA-ICM在痰液中的阳性检出率为37.3%(112/300),LBC在痰液中的阳性检出率为21.0%(63/300),差异有统计学意义(P＜0.01)。两种方法联合检查的痰检阳性率为38.7%(116/300),高于LBC,差异有统计学意义（P＜0.01）;也高于DNA-ICM,但差异无统计学意义（P＞0.05）。细胞DNA-ICM的敏感度为42.6%(112/263),特异度为100%(37/37);LBC敏感度为23.2%(61/263),特异度为94.6%(35/37),细胞DNA-ICM的敏感度高于LBC,差异有统计学意义(P＜0.01)。在病理组织分型不同的肺癌患者中,DNA-ICM 在鳞癌中的敏感度高于腺癌（P＜0.01）。DNA-ICM在早期肺癌及晚期肺癌检查结果中无统计学差异（P＞0.05）。结论:细胞DNA-ICM技术是一种敏感而特异的肺癌筛查技术,在肺癌早期诊断方面具有一定优势,可与LBC联合应用于肺癌的筛查。     

多发性骨髓瘤常用实验诊断方法评价

目的：比较血清蛋白电泳（琼脂糖凝胶法）、尿本周氏蛋白、骨髓细胞学等实验室指标对多发性骨髓瘤的诊断价值，找出经济、简便、快速的敏感指标。方法：分析多发性骨髓瘤的诊断过程，计算血清蛋白电泳、尿本周氏蛋白、骨髓细胞学诊断的敏感度和特异度。结果：琼脂糖凝胶血清蛋白电泳的敏感度是96．6％，特异度96．4％；尿本周氏蛋白的敏感度是10．5％，特异度98．2％；骨髓细胞学的敏感度是51．7％，特异度100％。结论：琼脂糖凝胶血清蛋白电泳的敏感度最高，且简便、快速、经济实用。     

膜式超薄液基细胞学检测技术在肺癌诊断中的应用

目的 探讨膜式超薄液基细胞学检测技术(TCT)在肺癌诊断中的应用价值.方法 收集143例肺癌患者和139例非肺癌患者的支气管肺泡灌洗液(BALF)和(或)纤维支气管镜刷片标本353个,同时进行TCT和直接涂片法检测,比较两种方法的敏感度和特异度.结果 TCT检测的敏感度为39.6%,特异度为99.4%,直接涂片法检测的敏感度为8.3%,特异度为100%,TCT检测的敏感度高于直接涂片法(P<0.01),特异度差异无统计学意义(P>0.05).BALF的TCT检测敏感度为41.5%,特异度为100%;直接涂片法诊断的敏感度为5.2%,特异度为100%.纤维支气管镜刷片的TCT检测敏感度为35.1%,特异度为96.4%;直接涂片法诊断的敏感度为15.8%,特异度为100%.与直接涂片法比较,两种标本的TCT检测敏感度较高(P<0.01),特异度差异无统计学意义(P>0.05).71例同时采集BALF和纤维支气管镜刷片患者,BALF TCT检测的敏感度(49.0%)高于纤维支气管镜刷片TCT检测的敏感度(32.7%,P<0.05).肺癌患者中,同时有TCT分类诊断和病理组织学诊断结果的标本有69个,TCT分类诊断和病理组织学诊断的总符合率为84.1%.结论 TCT检测能提高肺癌的诊断率,BALF的TCT检测可推广应用于临床.     

荧光原位杂交和尿细胞学检查对膀胱癌诊断意义的Meta分析

背景与目的：目前膀胱癌疗效和监测的主要方法是膀胱镜和尿细胞学检查,前者为侵人性检查,令患者感到不适;后者虽无创且特异性高．但敏感性太低,且受主观因素影响大。本研究拟对中、英文有关比较荧光原位杂交（fluorescence in situ hybridization,FISH）和尿细胞学检查诊断膀胱癌研究的结果进行系统分析,以明确FISH对膀胱癌的诊断意义。方法：采用Cochrane系统评价方法,MEDLINE（1966年1月～2008年6月）、EMBASE（1988年1月。2008年6月）、Cochrane图书馆、中国生物医学期刊文献数据库（CMCC,1979年。2008年6月）、CNKI数字图书馆（1979年1月～2008年6月）进行有关FISH和尿细胞学检查诊断膀胱癌文献的检索、质量评价和资料提取,采用MetaDiScl．4软件进行Meta分析。结果：共检索到相关研究242篇,排除230篇,符合纳入标准12篇进入Meta分析,涉及研究对象3430例。异质性检验提示无阈值效应,但存在其它原因导致的异质性。按随机效应模型进行Meta分析．FISH和尿细胞学诊断膀胱癌的准确度指标敏感度、特异度、阳性似然比、阴性似然比以及诊断优势比等汇总及95％C1分别为74％（71％-77％）VS．57％（54％-61％）、88％（86％-90％）VS．85％ （83％-87％）、6．18（3．56～10．73）VS．4．15（2．78～6．20）、0．29（0．19～0．45）VS．0．51（0．41～0．63）及24．17（9．33～62．64）VS．9．59（5．91～15．57）。FISH和尿脱落细胞学检查的敏感度随肿瘤分级、分期的升高而增高。综合受试者工作特征曲线下面积分别为0．8938、0．8247．Q^＊值分别为0．7847、0．7226。结论：FISH诊断膀胱癌的准确度较高,但对高分期的敏感度较细胞学低,目前尚不能取代传统的尿细胞学检查,但可作为膀胱癌术前诊断、术后监测和随访的指标。     

HER-2/neu amplification detected by fluorescence in situ hybridization in fine needle aspirates from primary breast cancer.

BACKGROUND: The HER-2/neu gene is amplified in 20-30% of human breast cancers and has been shown to have prognostic and predictive value for treatment with chemotherapy, hormone therapy and antibodies against the HER-2/neu domain (trastuzumab). The aim of our study was to evaluate the reliability of HER-2/neu determination by fluorescence in situ hybridization (FISH) on fine-needle aspirates (FNAs) from primary breast cancer patients by comparison with the results obtained by FISH and immunohistochemistry (IHC) on the corresponding histological sections. MATERIALS AND METHODS: HER-2/neu amplification was determined by FISH on 66 breast cancer FNAs. Twenty-three and 36 corresponding formalin-fixed, paraffin-embedded sections were assayed by FISH and by IHC, respectively, in order to detect HER-2/neu amplification and HER-2/neu protein expression. RESULTS: Twenty-seven per cent (18/66) of breast cancer FNAs showed amplification of HER-2/neu by FISH. Paired results by FISH cytology and FISH histology were available in 22 cases. Concordance was 91% (20/22). Paired results by FISH cytology and IHC were available in 36 cases. Concordance was 92% (33/36). Eighteen of 66 breast cancer FNAs were also submitted to flow cytometric DNA analysis. None of the diploid cases showed HER-2/neu amplification by FISH. Six out of the eight aneuploid cases were amplified and two were polysomic. CONCLUSIONS: HER-2/neu gene amplification can be reliably estimated by FISH on breast cancer FNAs and a good correlation has been found between FISH and IHC results from the corresponding histological sections.     

应用荧光原位杂交技术检测膀胱癌的研究

目的应用荧光原位杂交((fluorescence in situ hybridization,FISH)技术检测膀胱癌患者尿液脱落细胞中染色体异常,评估FISH在中国人群中诊断膀胱癌的作用。方法2007年1月至2008年8月,随机留取20例良性前列腺增生症患者的新鲜尿液,用3号和7号、17号及p16位两组混合探针,通过在尿液脱落细胞标本上进行FISH检测,建立正常人群的阈值;其后随机留取30例门诊膀胱镜活检证实的膀胱癌患者的尿液,同时进行尿液脱落细胞的细胞形态学分析及FISH检测,对比检查结果。结果3号、7号和17号染色体非整倍性改变及p16位点异常正常阈值分别为8.5%、7.1%、6.8%和9.2%,FISH与细胞学检查总敏感性分别为76.6%和43.3%(P<0.05)。T_(is)及T_a、T_1患者FISH检测的敏感性分别为80.0%和64.2%,脱落细胞组织学检测显示敏感性分别为40.0%和35.7%;T_(2-3)患者FISH的敏感性为90.9%,而脱落细胞组织学检测为54.7%(P<0.05),低级别尿路上皮癌FISH及细胞学敏感性分别为68.4%和31.6%;高级别分别为90.9%和63.6%。结论与尿液脱落细胞组织学检测相比,对尿液脱落细胞进行FISH检测可以提高膀胱癌的诊断率,FISH可以作为诊断膀胱癌的一种无创伤的新方法。     

Examination of Diagnostic Accuracy of UroVysion Fluorescence In Situ Hybridization for Bladder Cancer in a Single Community of Japanese Hospital Patients

Objective: UroVysion (Abbott Molecular, Inc., Illinois, USA) is based on multicolor fluorescence in situ hybridization(FISH). It has been used successfully in the USA following its Food and Drug Administration approval in 2001. However,the technology was not approved for use in Japan until 2017. Cystoscopy and urine cytology are the most frequentlyused examinations to detect bladder cancer in Japan, and there are only a few reports regarding the performance ofUroVysion. Therefore, the aim of this study is to examine the diagnostic accuracy of UroVysion FISH in Japanesepatients whose tumors are detected by cystoscopy before transurethral resection of bladder tumor (TURBT). Methods:From April 2018 to July 2018, a total of 40 patients who were diagnosed as having bladder tumors by cystoscopy, andtherefore underwent TURBT were registered in this study. One day before TURBT, urine cytology and UroVysionFISH were used in order to compare the accuracy with which they could detect bladder carcinoma, as confirmed bypathological results of TURBT. Results: The pathological results of TURBT showed urothelial carcinoma in 33 cases.Urine cytology showed positive results for 0 cases (0%), suspicious results for 10 cases (30.3%), and negative resultsfor 23 cases (69.7%). On the other hand, UroVysion FISH indicated 9 positive cases (27.3%) and 24 negative cases(72.7%). There were 19 cases of urothelial carcinoma (57.6%) that were not detected by either method. Conclusion:We conclude that UroVysion FISH alone is insufficient to detect bladder cancer and that cystoscopy is essential for theoptimum detection or follow up of bladder cancer cases in our hospital.     

Sensitive detection of tumour cells in effusions by combining cytology and fluorescence in situ hybridisation (FISH)

Diagnosis of malignant cells in effusions is important for staging procedures and resulting therapeutic decisions. Cytodiagnostics in effusions is sometimes difficult since reactive mesothelial cells can mimic malignant cells. We used fluorescence in situ hybridisation (FISH) in single-colour or if appropriate in dual-colour evaluation to detect chromosomal aberrations in effusion cells as markers of malignancy, to raise the diagnostic yield. Cytologic and FISH evaluations--by using probes representing several chromosomes always including chromosomes 11 and 17--were performed in 358 effusion fluids. Cytology was positive for malignancy in 44.4% of all effusions, whereas FISH was positive in 53.9% (P=0.0001). The combination of cytology and FISH was diagnostic for malignancy in 60.9% of effusions. Diagnostic superiority of FISH was demonstrated in effusions from breast cancer, lung cancer, pancreatic cancer, and in effusions from the entire group of gynaecological and gastrointestinal carcinomas. In transudates (effusion protein <2.5 g dl(-1)), malignant cells were detectable by cytology, FISH, and combined use of both methods in 18.6, 30, and 37.1% of effusions, respectively, suggesting that cytologic and molecular analysis should be performed also with transudates. In conclusion, FISH in combination with conventional cytology is a highly sensitive and specific diagnostic tool for detecting malignant cells in effusions.     

荧光原位杂交（FISH）辅助诊断胰胆管癌的技术及判读方法

目前对于临床上怀疑为胰胆管癌的患者,主要通过内窥镜下逆行胰胆管造影术（ERCP）和细胞刷检进行术前诊断。细胞刷检病理诊断虽然特异度高,但灵敏度较低。采用荧光原位杂交（FISH）方法检测胆管脱落细胞中3、7、17号染色体和p16缺失,可以作为临床胆管癌辅助鉴别诊断新的方法。此项技术虽然在国外的应用和研究已超过10年,但是我国尚未见应用于临床胰胆管癌的报道。我院已开展此项技术用于胰胆管癌的辅助诊断,并已发表相应的文章,但是很多希望开展此项技术的医院尚对此项技术的操作和判读存在疑问。本文详细讲解了运用FISH检测胆管脱落细胞中3、7、17号染色体和p16缺失来辅助诊断胰胆管癌的技术和判读方法。     

Concordant HER2 status between metastatic breast cancer cells in CSF and primary breast cancer tissue

It is not known whether the HER2 status of malignant CSF cells coincides with that of the original breast carcinoma cells. We investigated whether CSF cytology specimens were suitable to evaluate HER2 status by fluorescence in situ hybridization (FISH) in patient with leptomeningeal metastasis (LM). Both formalin-fixed paraffin-embedded (FFPE) breast cancer tissue and liquid based CSF cytology specimens were evaluated for HER2 status in 16 patients with LM. We evaluated HER2 gene amplification using FISH on destained CSF cytology slides containing a minimum of 20 malignant cells per slide, and compared these with the HER2 status by immunohistochemistry (IHC) or FISH in FFPE tissues. HER2 was considered positive when the HER2:CEP17 ratio was ≥2.0 or IHC 3+. Of 16 cases, four were HER2 positive and 12 were HER2 negative by FISH analysis in CSF cytology. All CSF-positive cases were HER2 positive by IHC in FFPE tissue. Of 12 HER2 FISH-negative cases in CSF cytology, 10 were HER2 negative (IHC 0 or 1+) and two were IHC 2+ in FFPE tissue. Two IHC 2+ cases had HER2:CEP17 ratios of 1.27 and 2.1, respectively, by FISH in FFPE tissue. As a result, the HER2 status concordance rate between metastatic breast cancer cells in CSF and FFPE primary tissue by IHC and FISH was very high. When CSF cytology specimens were appropriately prepared and had adequate cellularity without dry artifacts, the CSF cytology was suitable to evaluate HER2 status by FISH analysis in patients with LM.     

Combining cytology,TRAP assay,and FISH analysis for the detection of bladder cancer in symptomatic patients

BackgroundThere is a need to improve the performance of urine cytology in bladder cancer diagnosis. We assessed the diagnostic performance of (i) telomerase activity detected by telomeric repeat amplification protocol (TRAP) assay, (ii) cytology and TRAP assay in parallel, (iii) cytology in parallel with the in-series combination of TRAP assay and FISH analysis, and (iv) the in-series combination of TRAP assay and FISH analysis.Patients and methodsCross-sectional study of 289 consecutive patients who presented with urinary symptoms at a north Italian hospital between 2007 and 2008. All underwent cystoscopy and cytology evaluation, and conclusive results were available for TRAP assay and FISH analysis.ResultsSensitivity and specificity were 0.39 and 0.83, respectively, for cytology; 0.66 and 0.72 for TRAP; 0.78 and 0.60 for the combination of cytology and TRAP; 0.78 and 0.78 for the combination of cytology, TRAP, and FISH; and 0.65 and 0.93 for the combination of TRAP and FISH. All differences versus cytology alone were significant (P ≤ 0.011).ConclusionCompared with cytology alone, the combination of cytology, TRAP, and FISH provided the best trade-off between increase in sensitivity and loss in specificity, especially among non-bleeding patients, low-grade cancers, and early-stage cancers.     

膀胱癌荧光原位杂交检测及其临床意义

目的:分析膀胱移行细胞癌的染色体畸变情况,探讨荧光原位杂交(FISH)技术在膀胱癌的临床应用价值.方法:采用3、7、17号染色体着丝粒探针和9号染色体p16基因位点探针对56例膀胱移行细胞癌患者和20名健康人群的新鲜尿液进行FISH检测,统计染色体的畸变并分析其与病理分级、分期的关系.对所有病例同步进行尿细胞学分析.结果:膀胱癌患者尿脱落细胞核中3、7、17号染色体及9号染色体p16基因畸变率分别为58.9%、39.3%、58.9%和75.0%,各染色体畸变在膀胱癌不同分期之间的差异无统计学意义(P>0.05),3、7、17号染色体畸变在不同分级之间的差异具有统计学意义(P<0.05),四染色体探针组合诊断膀胱癌的总阳性率为80.4%;膀胱癌尿脱落细胞的FISH检出率明显高于尿细胞形态学.结论:膀胱癌的发生发展与染色体的畸变有关,膀胱癌尿脱落细胞的FISH检测,对膀胱癌的早期诊断、预后评估及复发监测等具有重要价值.     

The prognostic value of cytology and fluorescence in situ hybridization in the follow‐up of nonmuscle‐invasive bladder cancer after intravesical Bacillus Calmette‐Guérin therapy

Molecular markers reliably predicting failure or success of Bacillus Calmette‐Guérin (BCG) in the treatment of nonmuscle‐invasive urothelial bladder cancer (NMIBC) are lacking. The aim of our study was to evaluate the value of cytology and chromosomal aberrations detected by fluorescence in situ hybridization (FISH) in predicting failure to BCG therapy. Sixty‐eight patients with NMIBC were prospectively recruited. Bladder washings collected before and after BCG instillation were analyzed by conventional cytology and by multitarget FISH assay (UroVysion®, Abbott/Vysis, Des Plaines, IL) for aberrations of chromosomes 3, 7, 17 and 9p21. Persistent and recurrent bladder cancers were defined as positive events during follow‐up. Twenty‐six of 68 (38%) NMIBC failed to BCG. Both positive post‐BCG cytology and positive post‐BCG FISH were significantly associated with failure of BCG (hazard ratio (HR)= 5.1 and HR= 5.6, respectively; p < 0.001 each) when compared to those with negative results. In the subgroup of nondefinitive cytology (all except those with unequivocally positive cytology), FISH was superior to cytology as a marker of relapse (HR= 6.2 and 1.4, respectively). Cytology and FISH in post‐BCG bladder washings are highly interrelated and a positive result predicts failure to BCG therapy in patients with NMIBC equally well. FISH is most useful in the diagnostically less certain cytology categories but does not provide additional information in clearly malignant cytology. © 2009 UICC