Abstract
Purpose
Urine fluorescence in situ hybridization (FISH) has become a broadly used marker for noninvasive detection of bladder cancer (BC). However, it has been discussed whether the interpretation algorithm proposed by the manufacturer could be improved. Aim of the present study was to compare alternative evaluation strategies of FISH for detection of BC.
Methods
We included 1048 patients suspicious for BC, who underwent urine FISH examination before cystoscopy (diagnostic cohort). Herefrom, we selected 122 patients (prognostic cohort) with a history of non-muscle-invasive BC who were cystoscopically tumor free and received FISH analysis ahead of a follow-up period of 24 months. FISH results were interpreted by the algorithms of UroVysion™, Bubendorf et al. and Zellweger et al.
Results
In the diagnostic cohort, 228 patients (21.8%) had BC at time of evaluation; in the prognostic cohort 39 patients (32.0%) experienced tumor recurrence. Alterations in chromosome 3, 7 and 17 correlated with the presence of BC. Relative loss of 9p21 was associated with BC and higher risk for progression. The evaluation strategy proposed by Zellweger et al. showed highest accuracy of all FISH assessments. Performance of evaluation strategies differed in voided urine samples and samples obtained after mechanical manipulation.
Conclusions
The performance of FISH in BC diagnosis strongly depends on the interpretation criteria. Alternative evaluation methods partly show superior diagnostic performance compared to the manufacturer’s algorithm. The introduction of specific cutoffs for tetraploid cells improves specificity. Further modifications of the interpretation algorithm of the Urovysion® FISH assay have the potential to positively affect the value of this test in diagnosis and surveillance of BC.
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References
Babjuk M, Böhle A, Burger M, Capoun O, Cohen D, Compérat EM, Hernández V, Kaasinen E, Palou J, Rouprêt M, van Rhijn BW, Shariat SF, Soukup V, Sylvester RJ, Zigeuner R (2016) EAU Guidelines on Non–Muscle-invasive Urothelial Carcinoma of the Bladder: Update 2016. Eur Urol. doi:10.1016/j.eururo.2016.05.041
Bonberg N, Taeger D, Gawrych K et al (2013) Chromosomal instability and bladder cancer: the UroVysion(TM) test in the UroScreen study. BJU Int 112:372–382
Bonberg N, Pesch B, Behrens T et al (2014) Chromosomal alterations in exfoliated urothelial cells from bladder cancer cases and healthy men: a prospective screening study. BMC Cancer 14:854
Bubendorf L, Grilli B (2004) UroVysion multiprobe FISH in urinary cytology. Methods Mol Med 97:117–131
Bubendorf L, Grilli B, Sauter G et al (2001) Multiprobe FISH for enhanced detection of bladder cancer in voided urine specimens and bladder washings. Am J Clin Pathol 116:79–86
Budman LI, Kassouf W, Steinberg JR (2008) Biomarkers for detection and surveillance of bladder cancer. Can Urol Assoc J 2:212–221
Burger M, Catto JW, Dalbagni G et al (2013) Epidemiology and risk factors of urothelial bladder cancer. Eur Urol 63:234–241
Dimashkieh H, Wolff DJ, Smith TM et al (2013) Evaluation of urovysion and cytology for bladder cancer detection: a study of 1835 paired urine samples with clinical and histologic correlation. Cancer Cytopathol 121:591–597
Esposti PL, Moberger G, Zajicek J et al (1970) The cytologic diagnosis of transitional cell tumors of the urinary bladder and its histologic basis. A study of 567 cases of urinary-tract disorder including 170 untreated and 182 irradiated bladder tumors. Acta Cytol 14:145–155
Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C et al. (2014) Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet], GLOBOCAN 2012 v1.1, Lyon, France: International Agency for Research on Cancer. IOP Publishing Globocan. http://globocan.iarc.fr, Accessed 16 Jan 2015 and 8 sept 2015
https://www.abbottmolecular.com/en-us/staticAssets/pdfs/us/urovysion-package-insert.pdf, Accessed on 04 May 2016
Layfield LJ, Elsheikh TM, Fili A et al (2004) Papanicolaou Society of Cytopathology. 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 30:24–30
Lokeshwar VB, Getzenberg RH (2006) Voided Urine Markers, Biomarkers and early detection dilemma, Multitarget fluorescence in situ hybridization (Urovysion test). In: Lerner SP, Schoenberg MP, Sternberg CN (eds) Textbook of bladder cancer. Taylor & Francis, London, pp 211–223
Lokeshwar VB, Habuchi T, Grossman HB et al (2005) Bladder tumour markers beyond cytology: international consensus panel on bladder tumour markers. Urology 66:35–63
Moatamed NA, Apple SK, Moatamed F et al (2010) Inclusion of the uniform tetraploid cells reduces the specificity of the urine FISH assay. Mod Pathol 23:102A
Moatamed NA, Apple SK, Bennett CJ et al (2013) Exclusion of the uniform tetraploid cells significantly improves specificity of the urine FISH assay. Diagn Cytopathol 41:218–225
Riesz P, Lotz G, Paska C et al (2007) Detection of bladder cancer from the urine using fluorescence in situ hybridization technique. Pathol Oncol Res 13:187–194
Sarosdy MF, Schellhammer P, Bokinsky G et al (2002) Clinical evaluation of a multi-target fluorescent in situ hybridization assay for detection of bladder cancer. J Urol 168:1950–1954
Seideman C, Canter D, Kim P et al (2015) Multicenter evaluation of the role of UroVysion FISH assay in surveillance of patients with bladder cancer: does FISH positivity anticipate recurrence? World J Urol 33:1309–1313
Sokolova IA, Halling KC, Jenkins RB et al (2000) The development of a multitarget, multicolor fluorescence in situ hybridization assay for the detection of urothelial carcinoma in urine. J Mol Diagn 2:116–123
Stadler WM, Steinberg G, Yang X et al (2001) Alterations of the 9p21 and 9q33 chromosomal bands in clinical bladder cancer specimens by fluorescence in situ hybridization. Clin Cancer Res 6:1676–1682
Stenzl A, Hennenlotter J, Schilling D et al (2008) Can we still afford bladder cancer? Curr Opin Urol 18:488–492
Tilki D, Burger M, Dalbagni G (2011) Urine markers for detection and surveillance of non-muscle-invasive bladder cancer. Eur Urol 60:484–492
Todenhöfer T, Hennenlotter J, Kühs U et al (2012) Influence of urinary tract instrumentation and inflammation on the performance of urine markers for the detection of bladder cancer. Urology 79:620–624
Yoder BJ, Skacel M, Hedgepeth R et al (2007) 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 127:295–301
Zellweger T, Benz G, Cathomas G et al (2006) Multi-target fluorescence in situ hybridization in bladder washings for prediction of recurrent bladder cancer. Int J Cancer 119:1660–1665
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Mischinger, J., Guttenberg, L.P., 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 143, 677–685 (2017). https://doi.org/10.1007/s00432-016-2310-5
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DOI: https://doi.org/10.1007/s00432-016-2310-5