Skip to main content
Top
Published in: BMC Cancer 1/2017

Open Access 01-12-2017 | Research article

A prospective comparison of UroVysion FISH and urine cytology in bladder cancer detection

Authors: Hugh J. Lavery, Boriana Zaharieva, Andrew McFaddin, Nyla Heerema, Kamal S. Pohar

Published in: BMC Cancer | Issue 1/2017

Login to get access

Abstract

Background

UroVysion fluorescence in situ hybridization (uFISH) was reported to have superior sensitivity to urine cytology. However uFISH studies are limited by varying definitions of what is considered a positive result, absence of histopathology and small sample size. The aim of our study was to better determine the performance characteristics of uFISH and urine cytology by overcoming some of the deficiencies of the current literature.

Methods

Intraoperative bladder wash cytology and uFISH were collected prospectively on all patients. Strict definitions for positivity of uFISH and cytology were determined before initiating the study. A re-review of false-negative uFISH specimens was performed to analyze potential sources of error. Sixteen bladder tumors embedded in paraffin were analyzed by uFISH and compared with the result in the urine.

Results

One hundred and twenty-nine specimens were analyzed. Sensitivity was 67% and 69% (p = 0.54); specificity was 72% and 76% (p = 1.0), for uFISH and cytology, respectively. Thirty-two false negative uFISH samples were re-reviewed. Low grade tumors often showed cells with abnormal morphology and patchy DAPI staining but diploid chromosomal counts and a few high grade tumors had tetraploid counts but less than needed to interpret uFISH as positive. uFISH study of the tumors revealed three categories; positive in both tumor and urine (9), negative in both tumor and urine (5) and positive in tumor but negative in urine (2).

Conclusion

In a pathologically-confirmed analysis of bladder washed urine specimens, uFISH does not outperform urine cytology in cancer detection.
Literature
1.
go back to reference Sokolova IA, Halling KC, Jenkins RB, Burkhardt HM, Meyer RG, Seeling SA, et al. The development of a multitarget, multicolor fluorescence in situ hybridization assay for the detection of urothelial carcinom in urine. J Mol Diagn. 2000;2:116–23.CrossRefPubMedPubMedCentral Sokolova IA, Halling KC, Jenkins RB, Burkhardt HM, Meyer RG, Seeling SA, et al. The development of a multitarget, multicolor fluorescence in situ hybridization assay for the detection of urothelial carcinom in urine. J Mol Diagn. 2000;2:116–23.CrossRefPubMedPubMedCentral
2.
go back to reference Gofrit ON, Zorn KC, Silvestre J, Shalhav AL, Zagaja GP, Msezane LP, et al. The predictive value of multi-targeted fluorescent in-situ hybridization in patients with history of bladder cancer. Urol Oncol. 2008;26:246–9.CrossRefPubMed Gofrit ON, Zorn KC, Silvestre J, Shalhav AL, Zagaja GP, Msezane LP, et al. The predictive value of multi-targeted fluorescent in-situ hybridization in patients with history of bladder cancer. Urol Oncol. 2008;26:246–9.CrossRefPubMed
3.
go back to reference Maffezzini M, Campodonico F, Capponi G, Canepa G, Casazza S, Bandelloni R, et al. Prognostic significance of fluorescent in situ hybridisation in the follow-up of non-muscle-invasive bladder cancer. Anticancer Res. 2010;30:4761–5.PubMed Maffezzini M, Campodonico F, Capponi G, Canepa G, Casazza S, Bandelloni R, et al. Prognostic significance of fluorescent in situ hybridisation in the follow-up of non-muscle-invasive bladder cancer. Anticancer Res. 2010;30:4761–5.PubMed
4.
go back to reference Lotan Y, Shariat SF, Schmitz-Dräger BJ, Sanchez-Carbayo M, Jankevicius F, Racioppi M, et al. Considerations on implementing diagnostic markers into clinical decision making in bladder cancer. Urol Oncol. 2010;28:441–8.CrossRefPubMed Lotan Y, Shariat SF, Schmitz-Dräger BJ, Sanchez-Carbayo M, Jankevicius F, Racioppi M, et al. Considerations on implementing diagnostic markers into clinical decision making in bladder cancer. Urol Oncol. 2010;28:441–8.CrossRefPubMed
5.
go back to reference Halling KC, King W, Sokolova IA, Meyer RG, Burkhardt HM, Halling AC, et al. A comparison of cytology and fluorescence in situ hybridization for the detection of urothelial carcinoma. J Urol. 2000;164:1768–75.CrossRefPubMed Halling KC, King W, Sokolova IA, Meyer RG, Burkhardt HM, Halling AC, et al. A comparison of cytology and fluorescence in situ hybridization for the detection of urothelial carcinoma. J Urol. 2000;164:1768–75.CrossRefPubMed
6.
go back to reference Sarosdy MF, Schellhammer P, Bokinsky G, Kahn P, Chao R, Yore L, et al. Clinical evaluation of a multi-target fluorescent in situ hybridization assay for the detection of bladder cancer. J Urol. 2002;168:1950–4.CrossRefPubMed Sarosdy MF, Schellhammer P, Bokinsky G, Kahn P, Chao R, Yore L, et al. Clinical evaluation of a multi-target fluorescent in situ hybridization assay for the detection of bladder cancer. J Urol. 2002;168:1950–4.CrossRefPubMed
7.
go back to reference Skacel M, Fahmy M, Brainard JA, Pettay JD, Biscotti CV, Liou LS, et al. Multitarget fluorescence in situ hybridization assay detects transitional cell carcinoma in the majority of patients with bladder cancer and atypical or negative urine cytology. J Urol. 2003;169:2101–5.CrossRefPubMed Skacel M, Fahmy M, Brainard JA, Pettay JD, Biscotti CV, Liou LS, et al. Multitarget fluorescence in situ hybridization assay detects transitional cell carcinoma in the majority of patients with bladder cancer and atypical or negative urine cytology. J Urol. 2003;169:2101–5.CrossRefPubMed
8.
go back to reference Sarosdy MF, Kahn PR, Ziffer MD, Love WR, Barkin J, Abara EO, et al. Use of a multitarget fluorescence in situ hybridization assay to diagnose bladder cancer in patients with hematuria. J Urol. 2006;176:44–7.CrossRefPubMed Sarosdy MF, Kahn PR, Ziffer MD, Love WR, Barkin J, Abara EO, et al. Use of a multitarget fluorescence in situ hybridization assay to diagnose bladder cancer in patients with hematuria. J Urol. 2006;176:44–7.CrossRefPubMed
9.
go back to reference Bergman J, Reznichek RC, Rajfer J. Surveillance of patients with bladder carcinoma using fluorescent in-situ hybridization on bladder washings. BJU Int. 2008;101:26–9.PubMed Bergman J, Reznichek RC, Rajfer J. Surveillance of patients with bladder carcinoma using fluorescent in-situ hybridization on bladder washings. BJU Int. 2008;101:26–9.PubMed
10.
go back to reference Fritsche HM, Burger M, Dietmaier W, Denzinger S, Bach E, Otto W, et al. Multicolor FISH (UroVysion) facilitates follow-up of patients with high-grade urothelial carcinoma of the bladder. Am J Clin Pathol. 2010;134:597–603.CrossRefPubMed Fritsche HM, Burger M, Dietmaier W, Denzinger S, Bach E, Otto W, et al. Multicolor FISH (UroVysion) facilitates follow-up of patients with high-grade urothelial carcinoma of the bladder. Am J Clin Pathol. 2010;134:597–603.CrossRefPubMed
11.
go back to reference Caraway NP, Khanna A, Fernandez RL, Payne L, Bassett Jr RL, Zhang HZ, et al. Fluorescence in situ hybridization for detecting urothelial carcinoma: a clinicopathologic study. Cancer Cytopathol. 2010;118:259–68.CrossRefPubMedPubMedCentral Caraway NP, Khanna A, Fernandez RL, Payne L, Bassett Jr RL, Zhang HZ, et al. Fluorescence in situ hybridization for detecting urothelial carcinoma: a clinicopathologic study. Cancer Cytopathol. 2010;118:259–68.CrossRefPubMedPubMedCentral
12.
go back to reference Galván AB, Salido M, Espinet B, Placer J, Pijuan L, Juanpere N, et al. A multicolor fluorescence in situ hybridization assay: a monitoring tool in the surveillance of patients with a history of non-muscle-invasive urothelial cell carcinoma: a prospective study. Cancer Cytopathol. 2011;119:395–403.CrossRefPubMed Galván AB, Salido M, Espinet B, Placer J, Pijuan L, Juanpere N, et al. A multicolor fluorescence in situ hybridization assay: a monitoring tool in the surveillance of patients with a history of non-muscle-invasive urothelial cell carcinoma: a prospective study. Cancer Cytopathol. 2011;119:395–403.CrossRefPubMed
13.
go back to reference Hajdinjak T. UroVysion FISH test for detecting urothelial cancers: meta-analysis of diagnostic accuracy and comparison with urinary cytology testing. Urol Oncol. 2008;26:646–51.CrossRefPubMed Hajdinjak T. UroVysion FISH test for detecting urothelial cancers: meta-analysis of diagnostic accuracy and comparison with urinary cytology testing. Urol Oncol. 2008;26:646–51.CrossRefPubMed
14.
go back to reference Veeramachaneni R, Nordberg ML, Shi R, Herrera GA, Turbat-Herrera EA. Evaluation of fluorescence in situ hybridization as an ancillary tool to urine cytology in diagnosing urothelial carcinoma. Diagn Cytopathol. 2003;28:301–7.CrossRefPubMed Veeramachaneni R, Nordberg ML, Shi R, Herrera GA, Turbat-Herrera EA. Evaluation of fluorescence in situ hybridization as an ancillary tool to urine cytology in diagnosing urothelial carcinoma. Diagn Cytopathol. 2003;28:301–7.CrossRefPubMed
15.
go back to reference Varella-Garcia M, Akduman B, Sunpaweravong P, Di Maria MV, Crawford ED. The UroVysion fluorescence in situ hybridization assay is an effective tool for monitoring recurrence of bladder cancer. Urol Oncol. 2004;22:16–9.CrossRefPubMed Varella-Garcia M, Akduman B, Sunpaweravong P, Di Maria MV, Crawford ED. The UroVysion fluorescence in situ hybridization assay is an effective tool for monitoring recurrence of bladder cancer. Urol Oncol. 2004;22:16–9.CrossRefPubMed
16.
go back to reference Daniely M, Rona R, Kaplan T, Olsfanger S, Elboim L, Zilberstien Y, et al. Combined analysis of morphology and fluorescence in situ hybridization significantly increases accuracy of bladder cancer detection in voided urine samples. Urology. 2005;66:1354–9.CrossRefPubMed Daniely M, Rona R, Kaplan T, Olsfanger S, Elboim L, Zilberstien Y, et al. Combined analysis of morphology and fluorescence in situ hybridization significantly increases accuracy of bladder cancer detection in voided urine samples. Urology. 2005;66:1354–9.CrossRefPubMed
17.
go back to reference Krause FS, Rauch A, Schrott KM, Engehausen DG. Clinical decisions for treatment of different staged bladder cancer based on multitarget fluorescence in situ hybridization assays? World J Urol. 2006;24:418–22.CrossRefPubMed Krause FS, Rauch A, Schrott KM, Engehausen DG. Clinical decisions for treatment of different staged bladder cancer based on multitarget fluorescence in situ hybridization assays? World J Urol. 2006;24:418–22.CrossRefPubMed
18.
go back to reference Bubendorf L, Grilli B, Sauter G, Mihatsch MJ, Gasser TC, Dalquen P. Multiprobe FISH for enhanced detection of bladder cancer in voided urine specimens and bladder washings. Am J Clin Pathol. 2011;116:79–86.CrossRef Bubendorf L, Grilli B, Sauter G, Mihatsch MJ, Gasser TC, Dalquen P. Multiprobe FISH for enhanced detection of bladder cancer in voided urine specimens and bladder washings. Am J Clin Pathol. 2011;116:79–86.CrossRef
19.
go back to reference Dimashkieh H, Wolff DJ, Smith TM, Houser PM, Nietert PJ, Yang J. Evaluation of urovysion and cytology for bladder cancer detection: a study of 1835 paired urine samples with clinical and histologic correlation. Cancer Cytopathol. 2013;121:591–7.CrossRefPubMedPubMedCentral Dimashkieh H, Wolff DJ, Smith TM, Houser PM, Nietert PJ, Yang J. Evaluation of urovysion and cytology for bladder cancer detection: a study of 1835 paired urine samples with clinical and histologic correlation. Cancer Cytopathol. 2013;121:591–7.CrossRefPubMedPubMedCentral
20.
go back to reference Brimo F, Vollmer RT, Case B, Aprikian A, Kassouf W, Auger M. Accuracy of urine cytology and the significance of an atypical category. Am J Clin Pathol. 2009;132:785–93.CrossRefPubMed Brimo F, Vollmer RT, Case B, Aprikian A, Kassouf W, Auger M. Accuracy of urine cytology and the significance of an atypical category. Am J Clin Pathol. 2009;132:785–93.CrossRefPubMed
21.
go back to reference Dangle PP, Gong MC, Bahnson RR, Pohar KS. How do commonly performed lymphadenectomy templates influence bladder cancer nodal stage? J Urol. 2010;183:499–503.CrossRefPubMed Dangle PP, Gong MC, Bahnson RR, Pohar KS. How do commonly performed lymphadenectomy templates influence bladder cancer nodal stage? J Urol. 2010;183:499–503.CrossRefPubMed
22.
go back to reference UroVysion fluorescence in situ hybridization promotional literature and package insert, Abbott molecular. Des Plaines. IL, USA. UroVysion fluorescence in situ hybridization promotional literature and package insert, Abbott molecular. Des Plaines. IL, USA.
24.
go back to reference Reid-Nicholson MD, Ramalingam P, Adeagbo B, Cheng N, Peiper SC, Terris MK. The use of Urovysion fluorescence in situ hybridization in the diagnosis and surveillance of non-urothelial carcinoma of the bladder. Mod Pathol. 2009;22:119–27.CrossRefPubMed Reid-Nicholson MD, Ramalingam P, Adeagbo B, Cheng N, Peiper SC, Terris MK. The use of Urovysion fluorescence in situ hybridization in the diagnosis and surveillance of non-urothelial carcinoma of the bladder. Mod Pathol. 2009;22:119–27.CrossRefPubMed
25.
go back to reference Yoder BJ, Skacel M, Hedgepeth R, Babineau D, Ulchaker JC, Liou LS, et al. Reflex UroVysion testing of bladder cancer surveillance patients with equivocal or negative urine cytology: a prospective study with focus on the natural history of anticipatory positive findings. Am J Clin Pathol. 2007;127:295–301.CrossRefPubMed Yoder BJ, Skacel M, Hedgepeth R, Babineau D, Ulchaker JC, Liou LS, et al. Reflex UroVysion testing of bladder cancer surveillance patients with equivocal or negative urine cytology: a prospective study with focus on the natural history of anticipatory positive findings. Am J Clin Pathol. 2007;127:295–301.CrossRefPubMed
26.
go back to reference Zellweger T, Benz G, Cathomas G, Mihatsch MJ, Sulser T, Gasser TC, et al. Multi-target fluorescence in situ hybridization in bladder washings for prediction of recurrent bladder cancer. Int J Cancer. 2006;119:1660–5.CrossRefPubMed Zellweger T, Benz G, Cathomas G, Mihatsch MJ, Sulser T, Gasser TC, et al. Multi-target fluorescence in situ hybridization in bladder washings for prediction of recurrent bladder cancer. Int J Cancer. 2006;119:1660–5.CrossRefPubMed
27.
go back to reference Kipp BR, Halling KC, Campion MB, Wendel AJ, Karnes RJ, Zhang J, et al. Assessing the value of reflex fluorescence in situ hybridization testing in the diagnosis of bladder cancer when routine urine cytological examination is equivocal. J Urol. 2008;179:1296–301.CrossRefPubMed Kipp BR, Halling KC, Campion MB, Wendel AJ, Karnes RJ, Zhang J, et al. Assessing the value of reflex fluorescence in situ hybridization testing in the diagnosis of bladder cancer when routine urine cytological examination is equivocal. J Urol. 2008;179:1296–301.CrossRefPubMed
28.
29.
go back to reference Kamat AM, Karam JA, Grossman HB, Kader AK, Munsell M, Dinney CP. Prospective trial to identify optimal bladder cancer surveillance protocol: reducing costs while maximizing sensitivity. BJU Int. 2011;108:1119–23.CrossRefPubMed Kamat AM, Karam JA, Grossman HB, Kader AK, Munsell M, Dinney CP. Prospective trial to identify optimal bladder cancer surveillance protocol: reducing costs while maximizing sensitivity. BJU Int. 2011;108:1119–23.CrossRefPubMed
30.
go back to reference Youssef RF, Schlomer BJ, Ho R, Sagalowsky AI, Ashfaq R, Lotan Y. Role of fluorescence in situ hybridization in bladder cancer surveillance of patients with negative cytology. Urol Oncol. 2012;30:273–7.CrossRefPubMed Youssef RF, Schlomer BJ, Ho R, Sagalowsky AI, Ashfaq R, Lotan Y. Role of fluorescence in situ hybridization in bladder cancer surveillance of patients with negative cytology. Urol Oncol. 2012;30:273–7.CrossRefPubMed
31.
go back to reference Wild PJ, Fuchs T, Stoehr R, Zimmermann D, Frigerio S, Padberg B, et al. Detection of urothelial bladder cancer cells in voided urine can be improved by a combination of cytology and standardized microsatellite analysis. Cancer Epidemiol Biomark Prev. 2009;18:1798–806.CrossRef Wild PJ, Fuchs T, Stoehr R, Zimmermann D, Frigerio S, Padberg B, et al. Detection of urothelial bladder cancer cells in voided urine can be improved by a combination of cytology and standardized microsatellite analysis. Cancer Epidemiol Biomark Prev. 2009;18:1798–806.CrossRef
32.
go back to reference Kehinde EO, Al-Mulla F, Kapila K, Anim JT. Comparison of the sensitivity and specificity of urine cytology, urinary nuclear matrix protein-22 and multitarget fluorescence in situ hybridization assay in the detection of bladder cancer. Scand J Urol Nephrol. 2011;45:113–21.CrossRefPubMed Kehinde EO, Al-Mulla F, Kapila K, Anim JT. Comparison of the sensitivity and specificity of urine cytology, urinary nuclear matrix protein-22 and multitarget fluorescence in situ hybridization assay in the detection of bladder cancer. Scand J Urol Nephrol. 2011;45:113–21.CrossRefPubMed
33.
go back to reference Panzeri E, Conconi D, Antolini L, Redaelli S, Valsecchi MG, Bovo G, et al. Chromosomal aberrations in bladder cancer: fresh versus formalin fixed paraffin embedded tissue and targeted FISH versus wide microarray-based CGH analysis. PLoS One. 2011;6:e24237.CrossRefPubMedPubMedCentral Panzeri E, Conconi D, Antolini L, Redaelli S, Valsecchi MG, Bovo G, et al. Chromosomal aberrations in bladder cancer: fresh versus formalin fixed paraffin embedded tissue and targeted FISH versus wide microarray-based CGH analysis. PLoS One. 2011;6:e24237.CrossRefPubMedPubMedCentral
Metadata
Title
A prospective comparison of UroVysion FISH and urine cytology in bladder cancer detection
Authors
Hugh J. Lavery
Boriana Zaharieva
Andrew McFaddin
Nyla Heerema
Kamal S. Pohar
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2017
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-017-3227-3

Other articles of this Issue 1/2017

BMC Cancer 1/2017 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine