Portal de Periódicos da CAPES

Combinations of Urinary Biomarkers for Surveillance of Patients with Incident Nonmuscle Invasive Bladder Cancer: The European FP7 UROMOL Project

2012; Lippincott Williams & Wilkins; Volume: 189; Issue: 5 Linguagem: Inglês

10.1016/j.juro.2012.11.115

1527-3792

Tahlita C.M. Zuiverloon, Willemien Beukers, Kirstin A. van der Keur, Annemieke J.M. Nieuweboer, Thomas Reinert, Lars Dyrskjøt, Torben F. Ørntoft, Ellen C. Zwarthoff,

Esophageal Cancer Research and Treatment

No AccessJournal of UrologyInvestigative Urology1 May 2013Combinations of Urinary Biomarkers for Surveillance of Patients with Incident Nonmuscle Invasive Bladder Cancer: The European FP7 UROMOL Project Tahlita C.M. Zuiverloon, Willemien Beukers, Kirstin A. van der Keur, Annemieke J.M. Nieuweboer, Thomas Reinert, Lars Dyrskjot, Torben F. Orntoft, and Ellen C. Zwarthoff Tahlita C.M. ZuiverloonTahlita C.M. Zuiverloon Department of Urology, Erasmus Medical Center, Rotterdam, The Netherlands , Willemien BeukersWillemien Beukers Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands , Kirstin A. van der KeurKirstin A. van der Keur Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands , Annemieke J.M. NieuweboerAnnemieke J.M. Nieuweboer Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands , Thomas ReinertThomas Reinert Department of Molecular Medicine, Aarhus University Hospital, Denmark , Lars DyrskjotLars Dyrskjot Department of Molecular Medicine, Aarhus University Hospital, Denmark , Torben F. OrntoftTorben F. Orntoft Department of Molecular Medicine, Aarhus University Hospital, Denmark , and Ellen C. ZwarthoffEllen C. Zwarthoff Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands View All Author Informationhttps://doi.org/10.1016/j.juro.2012.11.115AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: We determined a combination of markers with optimal sensitivity to detect recurrence in voided urine after resection of an incident low grade, nonmuscle invasive bladder tumor. Materials and Methods: A total of 136 patients with G1/G2 nonmuscle invasive bladder tumor were included in the study at transurethral resection of the incident tumor. At least 3 followup urine samples were required for patient selection. DNA was extracted from the incident tumor and cell pellets of subsequently collected urine samples. We performed FGFR3, PIK3CA and RAS mutation analysis, and microsatellite and methylation analysis on tissue and urine DNA samples. Results: We obtained 716 urine samples. The 136 patients experienced a total of 552 recurrences during a median 3-year followup. Sensitivity for detecting a recurrent tumor varied between 66% and 68% for the molecular tests after patient stratification based on tumor DNA analysis. A combination of markers increased sensitivity but decreased the number of patients eligible for a certain test combination. Combining urine cytology with FGFR3 analysis without stratifying for FGFR3 status of the incident tumor increased sensitivity from 56% to 76%. Conclusions: A combination of markers increased the percentage of patients eligible for urine based followup and the sensitivity of recurrence detection. Adding FGFR3 analysis to urine cytology could be valuable for noninvasive followup of patients with nonmuscle invasive bladder cancer. References 1 : EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder. Eur Urol2008; 54: 303. Google Scholar 2 : Improved detection and treatment of bladder cancer using hexaminolevulinate imaging: a prospective, phase III multicenter study. J Urol2005; 174: 862. Link, Google Scholar 3 : The role of hexaminolevulinate fluorescence cystoscopy in bladder cancer. Nat Clin Pract Urol2007; 4: 542. Google Scholar 4 : The health economics of bladder cancer: a comprehensive review of the published literature. Pharmacoeconomics2003; 21: 1315. Google Scholar 5 : The cost of bladder tumour treatment and follow-up. Scand J Urol Nephrol2002; 36: 344. Google Scholar 6 : Detection of recurrent bladder cancer: NMP22 test or urine cytology?. Urol J2012; 9: 367. Google Scholar 7 : Detection of tumours of the urinary tract in voided urine. Scand J Urol Nephrol2008; 42: 147. Google Scholar 8 : Detection of bladder cancer in urine by a tumor suppressor gene hypermethylation panel. Clin Cancer Res2004; 10: 1887. Google Scholar 9 : Detection of methylated apoptosis-associated genes in urine sediments of bladder cancer patients. Clin Cancer Res2004; 10: 7457. Google Scholar 10 : Quantitation of promoter methylation of multiple genes in urine DNA and bladder cancer detection. J Natl Cancer Inst2006; 98: 996. Google Scholar 11 : Identification and validation of the methylated TWIST1 and NID2 genes through real-time methylation-specific polymerase chain reaction assays for the noninvasive detection of primary bladder cancer in urine samples. Eur Urol2010; 58: 96. Google Scholar 12 : Methylational urinalysis: a prospective study of bladder cancer patients and age stratified benign controls. Oncogene2006; 25: 1984. Google Scholar 13 : Comprehensive genome methylation analysis in bladder cancer: identification and validation of novel methylated genes and application of these as urinary tumor markers. Clin Cancer Res2011; 17: 5582. Google Scholar 14 : A methylation assay for the detection of non-muscle-invasive bladder cancer (NMIBC) recurrences in voided urine. BJU Int2012; 109: 941. Google Scholar 15 : Microsatellite analysis of voided-urine samples for surveillance of low-grade non-muscle-invasive urothelial carcinoma: feasibility and clinical utility in a prospective multicenter study (Cost-Effectiveness of Follow-Up of Urinary Bladder Cancer trial [CEFUB]). Eur Urol2009; 55: 659. Google Scholar 16 : Combined microsatellite and FGFR3 mutation analysis enables a highly sensitive detection of urothelial cell carcinoma in voided urine. Clin Cancer Res2003; 9: 257. Google Scholar 17 : Surveillance with microsatellite analysis of urine in bladder cancer patients treated by radiotherapy. Eur Urol2003; 43: 369. Google Scholar 18 : Prediction of progression of non-muscle-invasive bladder cancer by WHO 1973 and 2004 grading and by FGFR3 mutation status: a prospective study. Eur Urol2008; 54: 835. Google Scholar 19 : Prospective study of FGFR3 mutations as a prognostic factor in nonmuscle invasive urothelial bladder carcinomas. J Clin Oncol2006; 24: 3664. Google Scholar 20 : FGFR3 and Ras gene mutations are mutually exclusive genetic events in urothelial cell carcinoma. Oncogene2005; 24: 5218. Google Scholar 21 : PIK3CA mutations are an early genetic alteration associated with FGFR3 mutations in superficial papillary bladder tumors. Cancer Res2006; 66: 7401. Google Scholar 22 : Fibroblast growth factor receptor 3 mutation analysis on voided urine for surveillance of patients with low-grade non-muscle-invasive bladder cancer. Clin Cancer Res2010; 16: 3011. Google Scholar 23 : FGFR3, HRAS, KRAS, NRAS and PIK3CA mutations in bladder cancer and their potential as biomarkers for surveillance and therapy. PLoS One2010; 5: e13821. Google Scholar 24 : Histological typing of urinary bladder tumours. In: International Histological Classification of Tumours, No. 10. Geneva: World Health Organization1973: 485. Google Scholar 25 : A simple and fast method for the simultaneous detection of nine fibroblast growth factor receptor 3 mutations in bladder cancer and voided urine. Clin Cancer Res2005; 11: 7743. Google Scholar 26 : Methylation-specific MLPA (MS-MLPA): simultaneous detection of CpG methylation and copy number changes of up to 40 sequences. Nucleic Acids Res2005; 33: e128. Google Scholar 27 : Optimization of nonmuscle invasive bladder cancer recurrence detection using a urine based FGFR3 mutation assay. J Urol2011; 186: 707. Link, Google Scholar 28 : Urine markers for bladder cancer surveillance: a systematic review. Eur Urol2005; 47: 736. Google Scholar 29 : No mutations of FGFR3 in normal urothelium in the vicinity of urothelial carcinoma of the bladder harbouring activating FGFR3 mutations in patients with bladder cancer. Int J Cancer2009; 125: 2205. Google Scholar © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byBeukers W, van der Keur K, Kandimalla R, Vergouwe Y, Steyerberg E, Boormans J, Jensen J, Lorente J, Real F, Segersten U, Orntoft T, Malats N, Malmström P, Dyrskjot L and Zwarthoff E (2016) FGFR3, TERT and OTX1 as a Urinary Biomarker Combination for Surveillance of Patients with Bladder Cancer in a Large Prospective Multicenter StudyJournal of Urology, VOL. 197, NO. 6, (1410-1418), Online publication date: 1-Jun-2017. Volume 189Issue 5May 2013Page: 1945-1951Supplementary Materials Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.Keywordsreceptor, fibroblast growth factor, type 3neoplasm recurrencebiological markersurinary bladderurinary bladder neoplasmsMetricsAuthor Information Tahlita C.M. Zuiverloon Department of Urology, Erasmus Medical Center, Rotterdam, The Netherlands Equal study contribution. More articles by this author Willemien Beukers Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands Equal study contribution. More articles by this author Kirstin A. van der Keur Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands More articles by this author Annemieke J.M. Nieuweboer Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands More articles by this author Thomas Reinert Department of Molecular Medicine, Aarhus University Hospital, Denmark More articles by this author Lars Dyrskjot Department of Molecular Medicine, Aarhus University Hospital, Denmark More articles by this author Torben F. Orntoft Department of Molecular Medicine, Aarhus University Hospital, Denmark Financial interest and/or other relationship with AROS Applied Biotechnology. More articles by this author Ellen C. Zwarthoff Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands More articles by this author Expand All Advertisement PDF downloadLoading ...