Comparison of fluorescence <italic style="font-style: italic">in situ</italic> hybridization (FISH) and urine cytology in diagnosing urothelial carcinoma: a single-center retrospective cohort study

Zhiting WANG; Min REN; Tian XUE; Haochen WANG; Heng CHANG; Qianming BAI; Xiaoyan ZHOU; Xiaoli ZHU

doi:10.19401/j.cnki.1007-3639.2024.12.002

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Comparison of fluorescence in situ hybridization (FISH) and urine cytology in diagnosing urothelial carcinoma: a single-center retrospective cohort study

Article | 更新时间：2025-12-31

- Comparison of fluorescence in situ hybridization (FISH) and urine cytology in diagnosing urothelial carcinoma: a single-center retrospective cohort study
- China Oncology Vol. 34, Issue 12, Pages: 1080-1089(2024)
- 作者机构：
  
  1. 复旦大学附属肿瘤医院病理科，复旦大学上海医学院肿瘤学系，上海 200032
  2. 复旦大学病理研究所，上海 200032
- 作者简介：
  
  ZHU Xiaoli
- 基金信息：
- DOI：10.19401/j.cnki.1007-3639.2024.12.002
  CLC：
- Received：28 August 2024，
  
  Published：30 December 2024
- 稿件说明：
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Zhiting WANG, Min REN, Tian XUE, et al. Comparison of fluorescence in situ hybridization (FISH) and urine cytology in diagnosing urothelial carcinoma: a single-center retrospective cohort study[J]. China Oncology, 2024, 34(12): 1080-1089.
DOI：

Zhiting WANG, Min REN, Tian XUE, et al. Comparison of fluorescence in situ hybridization (FISH) and urine cytology in diagnosing urothelial carcinoma: a single-center retrospective cohort study[J]. China Oncology, 2024, 34(12): 1080-1089. DOI： 10.19401/j.cnki.1007-3639.2024.12.002.

摘要

背景与目的：

尿路上皮癌是泌尿系统常见的恶性肿瘤，其早期诊断对改善患者预后至关重要。本研究比较了荧光原位杂交（fluorescence

in situ

hybridization，FISH）、尿脱落细胞学及二者联合检测在尿路上皮癌及其不同亚型中的诊断效能。

方法：

本研究纳入了2022年1月—2023年12月行经尿道膀胱肿瘤切除术（transurethral resection of bladder tumor，TURBT）且符合入组标准及排除标准的患者，且获得复旦大学附属肿瘤医院伦理委员会批准（伦理批号：050432-4-2307E）。收集患者本次TURBT后病理学诊断结果及术前1周的FISH和脱落细胞学检测结果，对FISH、脱落细胞学及二者联合检测在尿路上皮癌中的诊断准确率、灵敏度和特异度进行统计学分析。本研究属于观察性研究，严格遵循《加强流行病学中观察性研究报告质量》（Strengthening the Reporting of Observational Studies in Epidemiology，STROBE）指南及《诊断准确性研究报告规范》（Standards for Reporting of Diagnostic Accuracy，STARD）中的各项条目。

结果：

本研究共纳入283例TURBT术后患者，其中136例为尿路上皮癌，147例为良性病变。136例尿路上皮癌中，根据病理学亚型分组，79（58.09%）例为浸润性尿路上皮癌，57（41.91%）例为非浸润性尿路上皮癌。根据恶性程度分组，112（82.35%）例为高级别尿路上皮癌，24（17.65%）例为低级别尿路上皮癌。以组织病理学诊断结果为金标准，136例尿路上皮癌中FISH、脱落细胞学、联合检测的准确率分别为79.51%、72.08%、77.39%，灵敏度分别为72.06%、58.82%、78.68%，特异度分别为86.39%、84.35%、76.19%。FISH、联合检测的曲线下面积（area under the curve，AUC）差异无统计学意义，但均高于脱落细胞学（0.792

0.7

16，

=0.006;0.774

0.716，

=0.004）;FISH与脱落细胞学相比，净重分类改善（net reclassification improvement，NRI）提升15.28%（

=0.006）。79例浸润性尿路上皮癌中，FISH的准确率高于脱落细胞学（86.28%

78.32%，

=0.011）;FISH、联合检测的灵敏度均高于脱落细胞学（86.08%

67.09%，

=0.004;91.14%

67.09%，

0.001），AUC值也高于脱落细胞学（0.808

0.713，

=0.004;0.784

0.713，

=0.007）;FISH与脱落细胞学相比，NRI值提升21.03%（

=0.003）。57例非浸润性尿路上皮癌中，3种检测方法的AUC值均较低（AUC

0.700）。112例高级别尿路上皮癌中，FISH的准确率、联合检测的灵敏度均高于脱落细胞学（84.94%

76.45%，

=0.005;89.29%

66.07%，

0.001），FISH及联合检测的AUC值也均高于脱落细胞学（0.847

0.752，

=0.002;0.827

0.752，

=0.001），FISH比脱落细胞学的NRI值提升19.01%（

=0.003）。24例低级别尿路上皮癌中，3种检测方法的AUC值均较低（AUC

0.600）。

结论：

尿路上皮癌中，尤其是浸润性和高级别尿路上皮癌，FISH的诊断效能优于脱落细胞学;FISH单独检测的准确率、灵敏度与联合检测相当，且特异性高于联合检测。在非浸润性或低级别尿路上皮癌中，3种检测方法的诊断效能均较低。

Abstract

Background and purpose:

Urothelial carcinoma (UC) is a prevalent malignant tumor of the urinary system

and early diagnosis is crucial for improving patient prognosis. This study evaluated the diagnostic efficacy of fluorescence in situ hybridization (FISH)

urine cytology and their combination for UC

as well as for its different subtypes.

Methods:

This study included patients who underwent transurethral resection of bladder tumor (TURBT) from January 2022 to December 2023 and approved by Ethics Commetce of Fudan Univesity Shanghai Cancer Center

No.: 050432-4-2307E) that met the inclusion and exclusion criteria. We collected TURBT pathological results and pre-procedure FISH and cytology results. Diagnostic accuracy

sensitivity and specificity of FISH

cytology an

d their combination were analyzed and compared for urothelial carcinoma. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist and Standards for Reporting of Diagnostic Accuracy (STARD) were followed for this study.

Results:

A total of 283 patients were enrolled in this study

136 were diagnosed with UC

and 147 were not. Of the 136 UC cases

79 (58.09%) were invasive and 57 (41.91%) were non-invasive. In terms of malignancy grade

112 (82.35%) were high-grade UC and 24 (17.65%) were low-grade UC. Using histopathology as the gold standard

the accuracy of FISH

cytology and their combination in diagnosing UC was 79.51%

72.08% and 77.39%

respectively; sensitivity was 72.06%

58.82% and 78.68%

respectively; specificity was 86.39%

84.35% and 76.19%

respectively. The area under the curve (AUC) for FISH and the combination was similar but higher than that for cytology (0.792

0.716

=0.006; 0.774

0.716

=0.004); the Net Reclassification Improvement (NRI) for FISH compared to cytology was 15.28% (

=0.006). In the 79 cases of invasive UC

FISH had higher accuracy than cytology (86.28%

78.32%

=0.011). The sensitivity of FISH and the combination was higher than that of cytology (86.08%

67.09%

=0.004; 91.14%

67.09%

0.001)

and the AUC values were also higher (0.808

0.713

=0.004; 0.784

0.713

=0.007). The NRI for FISH compared to cytology was 21.03% (

=0.003). In the 57 cases of non-invasive UC

the AUC values for all three methods were low (AUC

0.700). Among the 112 cases of high-grade UC

FISH had higher accuracy (84.94%

76.45%

=0.005)

and the combination had higher sensitivity (89.29%

66.07%

0.001) compared to cytology. The AUC values for FISH and the combination were also superior to that for cytology (0.847

0.752

=0.002; 0.827

0.752

=0.001). The NRI for FISH compared to cytology was 19.01% (

=0.003). In the 24 cases of low-grade UC

the AUC values for all three methods were low (AUC

0.600).

Conclusion:

For UC

particularly invasive and high-grade subtypes

FISH shows superior diagnostic efficacy compared to cytology. FISH alone offers accuracy and sensitivity comparable to the combination test

with higher specificity. In cases of non-invasive or low-grade UC

however

all three diagnostic methods demonstrate relatively low efficacy.

关键词

Keywords

references

BABJUK M , BURGER M , CAPOUN O , et al . European association of urology guidelines on non-muscle-invasive bladder cancer (Ta, T1, and carcinoma in situ ) [J ] . Eur Urol , 2022 , 81 ( 1 ): 75 - 94 .

SUNG H , FERLAY J , SIEGEL R L , et al . Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J ] . CA Cancer J Clin , 2021 , 71 ( 3 ): 209 - 249 .

ROUPRÊT M , BABJUK M , BURGER M , et al . European association of urology guidelines on upper urinary tract urothelial carcinoma: 2020 update [J ] . Eur Urol , 2021 , 79 ( 1 ): 62 - 79 . DOI: 10.1016/j.eururo.2020.05.042 http://doi.org/10.1016/j.eururo.2020.05.042

刘坤 . 超声对膀胱肿瘤诊断价值的评估 [D ] . 大连 : 大连医科大学 , 2018 .

LIU K . Evaluation of ultrasonography in the diagnosis of bladder tumors [D ] . Dalian Medical University , 2018 .

KONG C F , ZHANG S H , LEI Q F , et al . State-of-the-art advances of nanomedicine for diagnosis and treatment of bladder cancer [J ] . Biosensors , 2022 , 12 ( 10 ): 796 .

LIU C L , TSAI H W , PENG S L , et al . CDCP1 (CUB domain containing protein 1) is a potential urine-based biomarker in the diagnosis of low-grade urothelial carcinoma [J ] . PLoS One , 2023 , 18 ( 3 ): e0281873 .

YANG T , LI Y , LI J , et al . Diagnostic value comparison of urothelium carcinoma among urine exfoliated cells fluorescent in situ hybridization (FISH) examination, computerized tomography (CT) scan, and urine cytologic examination [J ] . Med Sci Monit , 2018 , 24 : 5788 - 5792 .

PYCHA S , TRENTI E , MIAN C , et al . Diagnostic value of Xpert® BC Detection, Bladder Epicheck®, Urovysion® FISH and cytology in the detection of upper urinary tract urothelial carcinoma [J ] . World J Urol , 2023 , 41 ( 5 ): 1323 - 1328 . DOI: 10.1007/s00345-023-04350-x http://doi.org/10.1007/s00345-023-04350-x

ZHANG J J , ZHENG S , GAO Y N , et al . A partial allelotyping of urothelial carcinoma of bladder in the Chinese [J ] . Carcinogenesis , 2004 , 25 ( 3 ): 343 - 347 . DOI: 10.1093/carcin/bgh015 http://doi.org/10.1093/carcin/bgh015

SOKOLOVA I A , HALLING K C , JENKINS R B , et al . The development of a multitarget, multicolor fluorescence in situ hybridization assay for the detection of urothelial carcinoma in urine [J ] . J Mol Diagn , 2000 , 2 ( 3 ): 116 - 123 .

TODENHÖFER T , HENNENLOTTER J , ESSER M , et al . Stepwise application of urine markers to detect tumor recurrence in patients undergoing surveillance for non-muscle-invasive bladder cancer [J ] . Dis Markers , 2014 , 2014 : 973406 .

GOMELLA L G , MANN M J , CLEARY R C , et al . Fluorescence in situ hybridization (FISH) in the diagnosis of bladder and upper tract urothelial carcinoma: the largest single-institution experience to date [J ] . Can J Urol , 2017 , 24 ( 1 ): 8620 - 8626 .

LAVERY H J , ZAHARIEVA B , MCFADDIN A , et al . A prospective comparison of UroVysion FISH and urine cytology in bladder cancer detection [J ] . BMC Cancer , 2017 , 17 ( 1 ): 247 . DOI: 10.1186/s12885-017-3227-3 http://doi.org/10.1186/s12885-017-3227-3

AALAMI A H , AALAMI F . Diagnostic performance of fluorescence in situ hybridization (FISH) in upper tract urothelial carcinoma (UTUC): a systematic review and meta-analysis [J ] . Int J Clin Oncol , 2022 , 27 ( 10 ): 1605 - 1615 .

JIN H Y , LIN T H , HAO J Q , et al . A comprehensive comparison of fluorescence in situ hybridization and cytology for the detection of upper urinary tract urothelial carcinoma: a systematic review and meta-analysis [J ] . Medicine , 2018 , 97 ( 52 ): e13859 .

SCIARRA A , LASCIO G D , DEL GIUDICE F , et al . Comparison of the clinical usefulness of different urinary tests for the initial detection of bladder cancer: a systematic review [J ] . Curr Urol , 2021 , 15 ( 1 ): 22 - 32 .

SASSA N , IWATA H , KATO M , et al . Diagnostic utility of UroVysion combined with conventional urinary cytology for urothelial carcinoma of the upper urinary tract [J ] . Am J Clin Pathol , 2019 , 151 ( 5 ): 469 - 478 . DOI: 10.1093/ajcp/aqy170 http://doi.org/10.1093/ajcp/aqy170

NAGAI T , OKAMURA T , YANASE T , et al . Examination of diagnostic accuracy of UroVysion fluorescence in situ hybridization for bladder cancer in a single community of Japanese hospital patients [J ] . Asian Pac J Cancer Prev , 2019 , 20 ( 4 ): 1271 - 1273 .

TODENHÖFER T , HENNENLOTTER J , ESSER M , et al . Combined application of cytology and molecular urine markers to improve the detection of urothelial carcinoma [J ] . Cancer Cytopathol , 2013 , 121 ( 5 ): 252 - 260 . DOI: 10.1002/cncy.21247 http://doi.org/10.1002/cncy.21247

KNOWLES M A , HURST C D . Molecular biology of bladder cancer: new insights into pathogenesis and clinical diversity [J ] . Nat Rev Cancer , 2015 , 15 ( 1 ): 25 - 41 . DOI: 10.1038/nrc3817 http://doi.org/10.1038/nrc3817

SHANG D H , LIU Y T , XU X H , et al . Diagnostic value comparison of CellDetect, fluorescent in situ hybridization (FISH), and cytology in urothelial carcinoma [J ] . Cancer Cell Int , 2021 , 21 ( 1 ): 465 .

COLLÀ RUVOLO C , WÜRNSCHIMMEL C , WENZEL M , et al . Comparison between 1973 and 2004/2016 World Health Organization grading in upper tract urothelial carcinoma treated with radical nephroureterectomy [J ] . Int J Clin Oncol , 2021 , 26 ( 9 ): 1707 - 1713 . DOI: 10.1007/s10147-021-01941-9 http://doi.org/10.1007/s10147-021-01941-9

STEWART B , WILD C . World cancer report 2014 [M ] . Lyon : IARC Press , 2014 : 738 - 750 .

HALLING K C , KING W , SOKOLOVA I A , et al . A comparison of cytology and fluorescence in situ hybridization for the detection of urothelial carcinoma [J ] . J Urol , 2000 , 164 ( 5 ): 1768 - 1775 .

MOONEN P M , MERKX G F , PEELEN P , et al . UroVysion compared with cytology and quantitative cytology in the surveillance of non-muscle-invasive bladder cancer [J ] . Eur Urol , 2007 , 51 ( 5 ): 1275 - 1280 ;discussion1280. DOI: 10.1016/j.eururo.2006.10.044 http://doi.org/10.1016/j.eururo.2006.10.044

NAGAI T , NAIKI T , ETANI T , et al . UroVysion fluorescence in situ hybridization in urothelial carcinoma: a narrative review and future perspectives [J ] . Transl Androl Urol , 2021 , 10 ( 4 ): 1908 - 1917 . DOI: 10.21037/tau-20-1207 http://doi.org/10.21037/tau-20-1207

COMPÉRAT E , AMIN M B , BERNEY D M , et al . What’s new in WHO fifth edition-urinary tract [J ] . Histopathology , 2022 , 81 ( 4 ): 439 - 446 .

SYDÉN F , BAARD J , BULTITUDE M , et al . Consultation on UTUC Ⅱ Stockholm 2022: diagnostics, prognostication, and follow-up-where are we today? [J ] . World J Urol , 2023 , 41 ( 12 ): 3395 - 3403 .

SAROSDY M F , SCHELLHAMMER P , BOKINSKY G , et al . Clinical evaluation of a multi-target fluorescent in situ hybridization assay for detection of bladder cancer [J ] . J Urol , 2002 , 168 ( 5 ): 1950 - 1954 .

HALLING K C , KING W , SOKOLOVA I A , et al . A comparison of BTA stat, hemoglobin dipstick, telomerase and Vysis UroVysion assays for the detection of urothelial carcinoma in urine [J ] . J Urol , 2002 , 167 ( 5 ): 2001 - 2006 .

SAVIC S , ZLOBEC I , THALMANN G N , et al . The prognostic value of cytology and fluorescence in situ hybridization in the follow-up of nonmu scle-invasive bladder cancer after intravesical Bacillus Calmette-Guérin therapy [J ] . Int J Cancer , 2009 , 124 ( 12 ): 2899 - 2904 .

鲁颂献 . 荧光原位杂交(FISH)技术在诊断尿路上皮癌中的研究 [D ] . 吉林大学 , 2013 .

LU S X . Study on fluorescence in situ hybridization (FISH) technique in diagnosis of urothelial carcinoma [D ] . Jilin University , 2013 .

熊钻 , 梅玉峰 , 王春阳 , 等 . 荧光原位杂交技术联合尿脱落细胞学、膀胱肿瘤抗原对尿路上皮细胞肿瘤的诊断效能分析 [J ] . 国际检验医学杂志 , 2019 , 40 ( 10 ): 1201 - 1204 .

XIONG Z , MEI Y F , WANG C Y , et al . Performance analysis of fluorescence in situ hybridization combined with urinary exfoliative cytology and bladder tumor antigen in the diagnosis of urothelial cell carcinoma [J ] . Int J Lab Med , 2019 , 40 ( 10 ): 1201 - 1204 .

KE C J , HU Z Q , YANG C G . UroVysion TM fluorescence in situ hybridization in urological cancers: a narrative review and future perspectives [J ] . Cancers , 2022 , 14 ( 21 ): 5423 .

MOATAMED N A , APPLE S K , BENNETT C J , et al . Exclusion of the uniform tetraploid cells significantly improves specificity of the urine FISH assay [J ] . Diagn Cytopathol , 2013 , 41 ( 3 ): 218 - 225 . DOI: 10.1002/dc.21831 http://doi.org/10.1002/dc.21831

DALQUEN P , KLEIBER B , GRILLI B , et al . DNA image cytometry and fluorescence in situ hybridization for noninvasive detection of urothelial tumors in voided urine [J ] . Cancer , 2002 , 96 ( 6 ): 374 - 379 .

TAPIA C , GLATZ K , OBERMANN E C , et al . Evaluation of chromosomal aberrations in patients with benign conditions and reactive changes in urinary cytology [J ] . Cancer Cytopathol , 2011 , 119 ( 6 ): 404 - 410 . DOI: 10.1002/cncy.20171 http://doi.org/10.1002/cncy.20171

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Comparison of fluorescence in situ hybridization (FISH) and urine cytology in diagnosing urothelial carcinoma: a single-center retrospective cohort study

DOI：10.19401/j.cnki.1007-3639.2024.12.002

摘要

Abstract

关键词

Keywords

references