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Urine Cytology and Emerging Biomarkers

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Management of Urothelial Carcinoma

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Abstract

About 70% of bladder cancer diagnosis has non-muscle invasive character; however, 31–78% of them experiences recurrence and 1–45% of them progression within 5 years. For this reason, close monitoring for early detection of recurrence is essential in following up of NMIBC patients. Current gold standard for surveillance of NMIBC is based on visual inspection through cystoscopy and concurrent urine cytology examination. Urine cytology offers high specificity (83–99%) and sensitivity (84%) in high-grade lesion of UCC; however it affords only 16% of sensitivity for low-grade lesion. To overcome this limitation of urine cytology, many novel urine-based biomarkers have been developed, and some of them successfully settle on clinical practice. NMP22 (nuclear matrix protein 22), BTA (bladder tumor antigen), FDP (fibrin/fibrinogen degradation products), UroVysion (FISH), and ImmunoCyt are currently FDA (Food and Drug Administration)-approved biomarkers for detection of UCC in bladder. Most of these novel biomarkers show higher sensitivity but lower specificity than conventional urine cytology. Thus, a study for finding another useful marker and improving shortcoming of currently available biomarkers is actively on progress.

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References

  1. Raitanen MP, Aine R, Rintala E, Kallio J, Rajala P, Juusela H, et al. Differences between local and review urinary cytology in diagnosis of bladder cancer. An interobserver multicenter analysis. Eur Urol. 2002;41:284–9. https://doi.org/10.1016/S0302-2838(02)00006-4.

    Article  PubMed  Google Scholar 

  2. Yafi FA, Brimo F, Steinberg J, Aprikian AG, Tanguay S, Kassouf W. Prospective analysis of sensitivity and specificity of urinary cytology and other urinary biomarkers for bladder cancer. Urol Oncol. 2015;33:66e25–31. https://doi.org/10.1016/j.urolonc.2014.06.008.

    Article  Google Scholar 

  3. Lotan Y, Roehrborn CG. Sensitivity and specificity of commonly available bladder tumor markers versus cytology: results of a comprehensive literature review and meta-analyses. Urology. 2003;61:109–18. https://doi.org/10.1016/S0090-4295(02)02136-2.

    Article  PubMed  Google Scholar 

  4. Alberto P, Margarita A. Correlation between the cytology of urine sediment in fresh sample and smears stained by Papanicolaou and Giemsa methods. J Cytol. 2014;31:25. https://doi.org/10.4103/0970-9371.130666.

    Article  Google Scholar 

  5. Viswanath S, Zelhof B, Ho E, Sethia K, Mills R. Is routine urine cytology useful in the haematuria clinic? Ann R Coll Surg Engl. 2008;90:153–5. https://doi.org/10.1308/003588408X242006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Ok BG, Ji YS, Ko YH, Song PH. Usefulness of urine cytology as a routine work-up in the detection of recurrence in patients with prior non-muscle-invasive bladder cancer: practicality and cost-effectiveness. Korean J Urol. 2014;55:650–5. https://doi.org/10.4111/kju.2014.55.10.650.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Keller AK, Jensen JB. Voided urine versus bladder washing cytology for detection of urothelial carcinoma: which is better? Scand J Urol. 2017;51:290–2. https://doi.org/10.1080/21681805.2017.1310130.

    Article  PubMed  Google Scholar 

  8. Zhang ML, Rosenthal DL, VandenBussche CJ. The cytomorphological features of low-grade urothelial neoplasms vary by specimen type. Cancer Cytopathol. 2016;124:552–64. https://doi.org/10.1002/cncy.21716.

    Article  CAS  PubMed  Google Scholar 

  9. Powsner SM, Costa J, Homer RJ. Clinicians are from mars and pathologists are from venus: clinician interpretation of pathology reports. Arch Pathol Lab Med. 2000;124:1040–6. https://doi.org/10.1043/0003-9985(2000)124<1040:CAFMAP>2.0.CO;2.

    Article  CAS  PubMed  Google Scholar 

  10. Layfield LJ, Elsheikh TM, Fili A, Nayar R, Shidham V. Review of the state of the art and recommendations of the Papanicolaou society of cytopathology for urinary cytology procedures and reporting: the Papanicolaou society of cytopathology practice guidelines task force. Diagn Cytopathol. 2004;30:24–30. https://doi.org/10.1002/dc.10401.

    Article  PubMed  Google Scholar 

  11. Barkan GA, Wojcik EM, Nayar R, Savic-Prince S, Quek ML, Kurtycz DFI, et al. The Paris system for reporting urinary cytology: the quest to develop a standardized terminology. Acta Cytol. 2016;60:185–97. https://doi.org/10.1159/000446270.

    Article  PubMed  Google Scholar 

  12. Hassan M, Solanki S, Kassouf W, Kanber Y, Caglar D, Auger M, et al. Impact of implementing the Paris system for reporting urine cytology in the performance of urine cytology. Am J Clin Pathol. 2016;146:384–90. https://doi.org/10.1093/ajcp/aqw127.

    Article  PubMed  Google Scholar 

  13. Cowan ML, Rosenthal DL, VandenBussche CJ. Improved risk stratification for patients with high-grade urothelial carcinoma following application of the Paris system for reporting urinary cytology. Cancer Cytopathol. 2017;125:427–34. https://doi.org/10.1002/cncy.21843.

    Article  CAS  PubMed  Google Scholar 

  14. Bertsch EC, Siddiqui MT, Ellis CL. The Paris system for reporting urinary cytology improves correlation with surgical pathology biopsy diagnoses of the lower urinary tract. Diagn Cytopathol. 2018;46:221–7. https://doi.org/10.1002/dc.23878.

    Article  PubMed  Google Scholar 

  15. Wang Y, Auger M, Kanber Y, Caglar D, Brimo F. Implementing the Paris system for reporting urinary cytology results in a decrease in the rate of the “atypical” category and an increase in its prediction of subsequent high-grade urothelial carcinoma. Cancer Cytopathol. 2018;126(3):207–14. https://doi.org/10.1002/cncy.21958.

    Article  CAS  PubMed  Google Scholar 

  16. Parker J, Spiess PE. Current and emerging bladder Cancer urinary biomarkers. Sci World J. 2011;11:1103–12. https://doi.org/10.1100/tsw.2011.104.

    Article  CAS  Google Scholar 

  17. Carpinito GA, Stadler WM, Briggman JV, Chodak GW, Church PA, Lamm DL, et al. Urinary nuclear matrix protein as a marker for transitional cell carcinoma of the urinary tract. J Urol. 1996;156:1280–5.

    Article  CAS  Google Scholar 

  18. Jamshidian H, Kor K, Djalali M. Urine concentration of nuclear matrix protein 22 for diagnosis of transitional cell carcinoma of bladder. Urol J. 2008;5:243–7.

    PubMed  Google Scholar 

  19. Chou R, Gore JL, Buckley D, Fu R, Gustafson K, Griffin JC, et al. Urinary biomarkers for diagnosis of bladder cancer: a systematic review and meta-analysis. Ann Intern Med. 2015;163:922–31. https://doi.org/10.7326/M15-0997.

    Article  PubMed  Google Scholar 

  20. Schmitz-Dräger BJ, Todenhöfer T, van Rhijn B, Pesch B, Hudson MA, Chandra A, et al. Considerations on the use of urine markers in the management of patients with low−/intermediate-risk non-muscle invasive bladder cancer. Urol Oncol. 2014;32:1061–8. https://doi.org/10.1016/j.urolonc.2013.10.010.

    Article  PubMed  Google Scholar 

  21. Chang SS, Boorjian SA, Chou R, Clark PE, Daneshmand S, Konety BR, et al. Diagnosis and treatment of non-muscle invasive bladder cancer: AUA/SUO guideline. J Urol. 2016;196:1021–9. https://doi.org/10.1016/j.juro.2016.06.049.

    Article  PubMed  Google Scholar 

  22. Urology P, Nordwest H, Hospital A. A comparison of urinary nuclear matrix protein-22 and bladder tumour antigen tests with voided urinary cytology in detecting and following bladder cancer: the prognostic value of false-positive results. BJU Int. 2001;88(7):692–701.

    Google Scholar 

  23. Frantzi M, Latosinska A, Flühe L, Hupe MC, Critselis E, Kramer MW, et al. Developing proteomic biomarkers for bladder cancer: towards clinical application. Nat Rev Urol. 2015;12:317–30. https://doi.org/10.1038/nrurol.2015.100.

    Article  PubMed  Google Scholar 

  24. Lu J, Getz G, Miska EA, Alvarez-saavedra E, Lamb J, Peck D, et al. MicroRNA expression profiles classify human cancers. Nature. 2005;435:834–48. https://doi.org/10.1038/nature03702.

    Article  CAS  PubMed  Google Scholar 

  25. Mantripragada K, Caley M, Stephens P, Jones C, Kluwe L, Guha A, et al. Telomerase activity is a biomarker for high grade malignant peripheral nerve sheath tumors in neurofibromatosis type 1 individuals. Genes Chromosomes Cancer. 2008;47:238–46. https://doi.org/10.1002/gcc.

    Article  CAS  PubMed  Google Scholar 

  26. Zhang J, Zhao H, Gao Y, Zhang W. Secretory miRNAs as novel cancer biomarkers. Biochim Biophys Acta. 1826;2012:32–43. https://doi.org/10.1016/j.bbcan.2012.03.001.

    Article  CAS  Google Scholar 

  27. Hanke M, Hoefig K, Merz H, et al. A robust methodology to study urine microRNA as tumor marker: microRNA-126 and microRNA-182 are related to urinary bladder cancer. Urol Oncol. 2010;28:655–61. https://doi.org/10.1016/j.urolonc.2009.01.027.

    Article  CAS  PubMed  Google Scholar 

  28. Snowdon J, Boag S, Feilotter H, Izard J, Siemens DR. A pilot study of urinary microRNA as a biomarker for urothelial cancer. Can Urol Assoc J. 2013;7:28–33.

    Article  Google Scholar 

  29. Yamada Y, Enokida H, Kojima S, Kawakami K, Chiyomaru T, Yoshino H, et al. MiR-96 and miR-183 detection in urine serve as potential tumor markers of urothelial carcinoma: correlation with stage and grade, and comparison with urinary cytology. Cancer Sci. 2010;102:522–9. https://doi.org/10.1111/j.1349-7006.2010.01816.x.

    Article  CAS  PubMed  Google Scholar 

  30. Wang G, Chan ES, Kwan BC, Li PK, Yip SK, Szeto C, et al. Expression of microRNAs in the urine of patients with bladder cancer. Clin Genitourin Cancer. 2012;10(2):106–13. https://doi.org/10.1016/j.clgc.2012.01.001.

    Article  PubMed  Google Scholar 

  31. Yun SJ, Jeong P, Kim W, Kim TAEH, Lee Y, Song PH, et al. Cell-free microRNAs in urine as diagnostic and prognostic biomarkers of bladder cancer. Int J Oncol. 2012;41:1871–8. https://doi.org/10.3892/ijo.2012.1622.

    Article  CAS  PubMed  Google Scholar 

  32. Cheng Y, Deng X, Yang X, Li P, Zhang X, Li P, Tao J, Lu Q, Wang Z. Urine microRNAs as biomarkers for bladder cancer: a diagnostic meta-analysis. Onco Targets Ther. 2015;8:2089–96.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Mlcochova H, Hezova R, Stanik M, Slaby O. Urine microRNAs as potential noninvasive biomarkers in urologic cancers. Urol Oncol. 2014;32:1–9. https://doi.org/10.1016/j.urolonc.2013.04.011.

    Article  CAS  Google Scholar 

  34. Têtu B, Tiguert R, Harel F, Fradet Y. ImmunoCyt/uCyt+™ improves the sensitivity of urine cytology in patients followed for urothelial carcinoma. Mod Pathol. 2005;18:83–9. https://doi.org/10.1038/modpathol.3800262.

    Article  CAS  PubMed  Google Scholar 

  35. He H, Han C, Hao LIN, Zang G. ImmunoCyt test compared to cytology in the diagnosis of bladder cancer: a meta-analysis. Oncol Lett. 2016;12:83–8. https://doi.org/10.3892/ol.2016.4556.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Chee C, Ho K, Tan WP, Pathmanathan R, Tan K, Tan HM. Fluorescence-in-situ-hybridization in the surveillance of urothelial cancers: can use of cystoscopy or ureteroscopy be deferred? Asian Pacific J Cancer Prev. 2013;14:4057–9.

    Article  Google Scholar 

  37. Black PC, Brown GA, Dinney CP. Molecular markers of urothelial cancer and their use in the monitoring of superficial urothelial Cancer. J Clin Oncol. 2015;24:5528–35. https://doi.org/10.1200/JCO.2006.08.0895.

    Article  CAS  Google Scholar 

  38. 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. https://doi.org/10.1309/ADJL7E810U1H42BJ.

    Article  PubMed  Google Scholar 

  39. Hajdinjak T, Ph D. UroVysion FISH test for detecting urothelial cancers: meta-analysis of diagnostic accuracy and comparison with urinary cytology testing. Urol Oncol. 2008;26:646–51. https://doi.org/10.1016/j.urolonc.2007.06.002.

    Article  CAS  PubMed  Google Scholar 

  40. Hautmann SH, Iii GPH, Bono AV, Getzenberg RH, Goebell P, Schmitz-dräger BJ, et al. Bladder tumor markers beyond cytology: international consensus panel on bladder tumor markers. Urology. 2005;66:35–63. https://doi.org/10.1016/j.urology.2005.08.064.

    Article  PubMed  Google Scholar 

  41. Whitson J, Berry A, Carroll P, Konety B. A multicolour fluorescence in situ hybridization test predicts recurrence in patients with high-risk superficial bladder tumours undergoing intravesical therapy. BJU Int. 2009;104:336–9. https://doi.org/10.1111/j.1464-410X.2009.08375.x.

    Article  PubMed  Google Scholar 

  42. Savic S, Zlobec I, Thalmann GN, Engeler D, Schmauss M, Lehmann K, et al. The prognostic value of cytology and fluorescence in situ hybridization in the follow-up of nonmuscle-invasive bladder cancer after intravesical Bacillus erin therapy. Int J Cancer. 2009;124:2899–904. https://doi.org/10.1002/ijc.24258.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Urology, Seoul National University Hospital, Seoul, South Korea

    Jungyo Suh

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  1. Jungyo Suh
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  1. Department of Urology, Seoul National University Hospital, Seoul, Korea (Republic of)

    Ja Hyeon Ku

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Suh, J. (2019). Urine Cytology and Emerging Biomarkers. In: Ku, J. (eds) Management of Urothelial Carcinoma. Springer, Singapore. https://doi.org/10.1007/978-981-10-5502-7_5

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  • DOI: https://doi.org/10.1007/978-981-10-5502-7_5

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