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Fluorescence In Situ Hybridization (FISH) Testing in Urinary Tract Cytology

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Molecular Diagnostics in Cytopathology

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Abstract

Urothelial carcinoma (UC) is responsible for the majority of carcinomas arising in the urinary tract. Currently, the gold standard for detecting UCs and monitoring patients for recurrent UCs is cystoscopy with urinary cytology (UCyt). While historically many ancillary methods have been tested, including ImmunoCyt, BTA, and NMP22, none has been found to be sensitive, specific, and cost-effective enough to be routinely used. Of the ancillary methods, UroVysion® assay has been the most commonly used. UroVysion® is a fluorescence in situ hybridization (FISH) test that utilizes four single-stranded fluorescently labeled nucleic acid probes – three chromosome enumeration probes (CEP) for the chromosomes 3, 7, and 17 and the single locus-specific identifier (LSI) probe 9p21. The DNA probes are directly labeled with four different fluorescent dyes: SpectrumRed (CEP3), SpectrumGreen (CEP7), SpectrumAqua (CEP17), and SpectrumGold (LSI 9p21). UroVysion® should only be used in cases with equivocal urine cytology (i.e., atypical urothelial cells), since it does not add additional information when the urine cytology is negative (negative for high-grade urothelial carcinoma) or positive (positive for high-grade urothelial carcinoma). Even then, one should be cognizant of false-positive results, as can arise from tetraploid umbrella cells and polyomavirus cytopathic changes. It is also noteworthy that in cases of equivocal UCyt, a negative UroVysion® test does not rule out low-grade or high-grade urothelial carcinoma. An awareness of the limitations of this test (including conditions leading to false-positive interpretations and cost) with the judicious use of this test in select clinical circumstances is recommended.

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Abbreviations

AMH:

Asymptomatic microscopic hematuria

AUC:

Atypical urothelial cells

CEP:

Centromere enumeration probes

DAPI:

4′6-Diamidino-2-phenylindole

FISH:

Fluorescence in situ hybridization

H&E:

Hematoxylin and eosin

HGUC:

High-grade urothelial carcinoma

HPF:

High-power field

LGUN:

Low-grade urothelial neoplasia

LSI:

Locus-specific identifier

NHGUC:

Negative for high-grade urothelial carcinoma

QNS:

Quantity not sufficient

RBC:

Red blood cell

SHGUC:

Suspicious for high-grade urothelial carcinoma

TPS:

The Paris System for reporting urinary cytopathology

References

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017;67(1):7–30.

    Article  Google Scholar 

  2. Power NE, Izawa J. Comparison of guidelines on non-muscle invasive bladder Cancer (EAU, CUA, AUA, NCCN, NICE). Bladder Cancer. 2016;2(1):27–36.

    Article  Google Scholar 

  3. Yafi FA, Brimo F, Auger M, Aprikian A, Tanguay S, Kassouf W. Is the performance of urinary cytology as high as reported historically? A contemporary analysis in the detection and surveillance of bladder cancer. Urol Oncol. 2014;32(1):27.e21–6.

    Google Scholar 

  4. Amin MB, Smith SC, Reuter VE, et al. Update for the practicing pathologist: the international consultation on urologic disease-European association of urology consultation on bladder cancer. Mod Pathol. 2015;28(5):612–30.

    Article  Google Scholar 

  5. Wojcik EM. Urine cytology, DNA ploidy and morphometry. In: Lokeshwar VB, editor. Bladder tumors: molecular aspects and clinical management, cancer drug discovery and development. New York: Springer Science+Business Media; 2011. p. 79–90.

    Chapter  Google Scholar 

  6. Cajulis RS, Haines GK 3rd, Frias-Hidvegi D, McVary K, Bacus JW. Cytology, flow cytometry, image analysis, and interphase cytogenetics by fluorescence in situ hybridization in the diagnosis of transitional cell carcinoma in bladder washes: a comparative study. Diagn Cytopathol. 1995;13(3):214–23; discussion 224

    Article  CAS  Google Scholar 

  7. Meloni AM, Peier AM, Haddad FS, et al. A new approach in the diagnosis and follow-up of bladder cancer. FISH analysis of urine, bladder washings, and tumors. Cancer Genet Cytogenet. 1993;71(2):105–18.

    Article  CAS  Google Scholar 

  8. Cajulis RS, Haines GK 3rd, Frias-Hidvegi D, McVary K. Interphase cytogenetics as an adjunct in the cytodiagnosis of urinary bladder carcinoma. A comparative study of cytology, flow cytometry and interphase cytogenetics in bladder washes. Anal Quant Cytol Histol. 1994;16(1):1–10.

    CAS  PubMed  Google Scholar 

  9. Pycha A, Mian C, Haitel A, Hofbauer J, Wiener H, Marberger M. Fluorescence in situ hybridization identifies more aggressive types of primarily noninvasive (stage pTa) bladder cancer. J Urol. 1997;157(6):2116–9.

    Article  CAS  Google Scholar 

  10. Zhang FF, Arber DA, Wilson TG, Kawachi MH, Slovak ML. Toward the validation of aneusomy detection by fluorescence in situ hybridization in bladder cancer: comparative analysis with cytology, cytogenetics, and clinical features predicts recurrence and defines clinical testing limitations. Clin Cancer Res. 1997;3(12 Pt 1):2317–28.

    CAS  PubMed  Google Scholar 

  11. Sokolova IA, Halling KC, Jenkins RB, et al. The development of a multitarget, multicolor fluorescence in situ hybridization assay for the detection of urothelial carcinoma in urine. J Mol Diagn. 2000;2(3):116–23.

    Article  CAS  Google Scholar 

  12. Halling KC, King W, Sokolova IA, et al. A comparison of cytology and fluorescence in situ hybridization for the detection of urothelial carcinoma. J Urol. 2000;164(5):1768–75.

    Article  CAS  Google Scholar 

  13. Narayan VM, Adejoro O, Schwartz I, Ziegelmann M, Elliott S, Konety BR. The prevalence and impact of urinary marker testing in patients with bladder Cancer. J Urol. 2018;199(1):74–80.

    Article  Google Scholar 

  14. Sanli O, Dobruch J, Knowles MA, et al. Bladder cancer. Nat Rev Dis Primers. 2017;3:17022.

    Article  Google Scholar 

  15. Clinton T, Lotan Y. Review of the clinical approaches to the use of urine-based tumor markers in bladder cancer. Rambam Maimonides Med J. 2017;8(4):1–10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5652931/pdf/rmmj-8-4-e0040.pdf.

    Article  Google Scholar 

  16. Moyer VA, Force USPST. Screening for bladder cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2011;155(4):246–51.

    Article  Google Scholar 

  17. Steiner H, Bergmeister M, Verdorfer I, et al. Early results of bladder-cancer screening in a high-risk population of heavy smokers. BJU Int. 2008;102(3):291–6.

    Article  Google Scholar 

  18. Pesch B, Taeger D, Johnen G, et al. Screening for bladder cancer with urinary tumor markers in chemical workers with exposure to aromatic amines. Int Arch Occup Environ Health. 2014;87(7):715–24.

    Article  CAS  Google Scholar 

  19. Vickers AJ, Bennette C, Kibel AS, et al. Who should be included in a clinical trial of screening for bladder cancer?: a decision analysis of data from the prostate, lung, colorectal and ovarian Cancer screening trial. Cancer. 2013;119(1):143–9.

    Article  Google Scholar 

  20. Davis R, Jones JS, Barocas DA, et al. Diagnosis, evaluation and follow-up of asymptomatic microhematuria (AMH) in adults: AUA guideline. J Urol. 2012;188(6 Suppl):2473–81.

    Article  Google Scholar 

  21. Ordell Sundelin M, Jensen JB. Asymptomatic microscopic hematuria as a predictor of neoplasia in the urinary tract. Scand J Urol. 2017;51(5):373–5.

    Article  Google Scholar 

  22. Committee on Gynecologic Practice AUS. Committee opinion No.703: asymptomatic microscopic hematuria in women. Obstet Gynecol. 2017;129(6):e168–72.

    Article  Google Scholar 

  23. Linder BJ, Bass EJ, Mostafid H, Boorjian SA. Guideline of guidelines: asymptomatic microscopic haematuria. BJU Int. 2018;121(2):176–83.

    Article  Google Scholar 

  24. Schmitz-Drager BJ, Kuckuck EC, Zuiverloon TC, et al. Microhematuria assessment an IBCN consensus-based upon a critical review of current guidelines. Urol Oncol. 2016;34(10):437–51.

    Article  Google Scholar 

  25. Nepple KG, O’Donnell MA. The optimal management of T1 high-grade bladder cancer. Can Urol Ass J. 2009;3(6 Suppl 4):S188–92.

    Google Scholar 

  26. Chang SS, Boorjian SA, Chou R, et al. Diagnosis and treatment of non-muscle invasive bladder Cancer: AUA/SUO guideline. J Urol. 2016;196(4):1021–9.

    Article  Google Scholar 

  27. Liem E, Baard J, Cauberg ECC, et al. Fluorescence in situ hybridization as prognostic predictor of tumor recurrence during treatment with Bacillus Calmette-Guerin therapy for intermediate- and high-risk non-muscle-invasive bladder cancer. Medical Oncol (Northwood, London, England). 2017;34(10):172.

    Article  Google Scholar 

  28. Bubendorf L, Piaton E. UroVysion(R) multiprobe FISH in the triage of equivocal urinary cytology cases. Ann Pathol. 2012;32(6):e52–6, 438–43

    Article  Google Scholar 

  29. 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(3):273–7.

    Article  Google Scholar 

  30. Virk RK, Abro S, de Ubago JMM, et al. The value of the UroVysion(R) FISH assay in the risk-stratification of patients with “atypical urothelial cells” in urinary cytology specimens. Diagn Cytopathol. 2017;45(6):481–500.

    Article  Google Scholar 

  31. Bubendorf L, Grilli B. UroVysion multiprobe FISH in urinary cytology. Methods Mol Med. 2004;97:117–31.

    CAS  PubMed  Google Scholar 

  32. Savic S, Bubendorf L. Common fluorescence in situ hybridization applications in cytology. Arch Pathol Lab Med. 2016;140(12):1323–30.

    Article  Google Scholar 

  33. Zellweger T, Benz G, Cathomas G, et al. Multi-target fluorescence in situ hybridization in bladder washings for prediction of recurrent bladder cancer. Int J Cancer. 2006;119(7):1660–5.

    Article  CAS  Google Scholar 

  34. Moatamed NA, Apple SK, Bennett CJ, et al. Exclusion of the uniform tetraploid cells significantly improves specificity of the urine FISH assay. Diagn Cytopathol. 2013;41(3):218–25.

    Article  Google Scholar 

  35. Zhou AG, Liu Y, Cyr MS, et al. Role of Tetrasomy for the diagnosis of urothelial carcinoma using UroVysion fluorescent in situ hybridization. Arch Pathol Lab Med. 2016;140(6):552–9.

    Article  CAS  Google Scholar 

  36. Wojcik EM, Brownlie RJ, Bassler TJ, Miller MC. Superficial urothelial (umbrella) cells. A potential cause of abnormal DNA ploidy results in urine specimens. Anal Quant Cytol Histol. 2000;22(5):411–5.

    CAS  PubMed  Google Scholar 

  37. Mischinger J, Guttenberg LP, Hennenlotter J, et al. Comparison of different concepts for interpretation of chromosomal aberrations in urothelial cells detected by fluorescence in situ hybridization. J Cancer Res Clin Oncol. 2017;143(4):677–85.

    Article  CAS  Google Scholar 

  38. Hajdinjak T. UroVysion FISH test for detecting urothelial cancers: meta-analysis of diagnostic accuracy and comparison with urinary cytology testing. Urol Oncol. 2008;26(6):646–51.

    Article  CAS  Google Scholar 

  39. Horstmann M, Todenhofer T, Hennenlotter J, et al. Influence of age on false positive rates of urine-based tumor markers. World J Urol. 2013;31(4):935–40.

    Article  CAS  Google Scholar 

  40. Yoder BJ, Skacel M, Hedgepeth R, 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(2):295–301.

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, Loyola University Medical Center, Maywood, IL, USA

    Güliz A. Barkan & Stefan E. Pambuccian

Authors
  1. Güliz A. Barkan
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  2. Stefan E. Pambuccian
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Corresponding author

Correspondence to Güliz A. Barkan .

Editor information

Editors and Affiliations

  1. MD Anderson Cancer Center, The University of Texas, Houston, TX, USA

    Sinchita Roy-Chowdhuri

  2. Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

    Paul A. VanderLaan

  3. MD Anderson Cancer Center, The University of Texas, Houston, TX, USA

    John M. Stewart

  4. Department of Laboratory Medicine, University of Toronto, Toronto, ON, Canada

    Gilda da Cunha Santos

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Barkan, G.A., Pambuccian, S.E. (2019). Fluorescence In Situ Hybridization (FISH) Testing in Urinary Tract Cytology. In: Roy-Chowdhuri, S., VanderLaan, P., Stewart, J., Santos, G. (eds) Molecular Diagnostics in Cytopathology. Springer, Cham. https://doi.org/10.1007/978-3-319-97397-5_16

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  • DOI: https://doi.org/10.1007/978-3-319-97397-5_16

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  • Publisher Name: Springer, Cham

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  • Online ISBN: 978-3-319-97397-5

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