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Validation of a DNA Methylation-Mutation Urine Assay to Select Patients with Hematuria for Cystoscopy

2016; Lippincott Williams & Wilkins; Volume: 197; Issue: 3 Part 1 Linguagem: Inglês

10.1016/j.juro.2016.09.118

1527-3792

Kim E.M. van Kessel, Willemien Beukers, Irene Lurkin, Angelique Ziel‐van der Made, Kirstin A. van der Keur, Joost L. Boormans, Lars Dyrskjøt, Mirari Márquez, Torben F. Ørntoft, Francisco X. Real, Ulrika Segersten, Núria Malats, Per‐Uno Malmström, Wim Van Criekinge, Ellen C. Zwarthoff,

Epigenetics and DNA Methylation

No AccessJournal of UrologyAdult Urology1 Mar 2017Validation of a DNA Methylation-Mutation Urine Assay to Select Patients with Hematuria for Cystoscopy Kim E.M. van Kessel, Willemien Beukers, Irene Lurkin, Angelique Ziel-van der Made, Kirstin A. van der Keur, Joost L. Boormans, Lars Dyrskjøt, Mirari Márquez, Torben F. Ørntoft, Francisco X. Real, Ulrika Segersten, Núria Malats, Per-Uno Malmström, Wim Van Criekinge, and Ellen C. Zwarthoff Kim E.M. van KesselKim E.M. van Kessel Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands More articles by this author , Willemien BeukersWillemien Beukers Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands More articles by this author , Irene LurkinIrene Lurkin Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands More articles by this author , Angelique Ziel-van der MadeAngelique Ziel-van der Made Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands More articles by this author , Kirstin A. van der KeurKirstin A. van der Keur Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands More articles by this author , Joost L. BoormansJoost L. Boormans Department of Urology, Erasmus Medical Center, Rotterdam, The Netherlands More articles by this author , Lars DyrskjøtLars Dyrskjøt Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark More articles by this author , Mirari MárquezMirari Márquez Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre, Madrid More articles by this author , Torben F. ØrntoftTorben F. Ørntoft Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark More articles by this author , Francisco X. RealFrancisco X. Real Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre, Madrid Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain More articles by this author , Ulrika SegerstenUlrika Segersten Department of Surgical Sciences, Uppsala University, Uppsala, Sweden More articles by this author , Núria MalatsNúria Malats Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre, Madrid More articles by this author , Per-Uno MalmströmPer-Uno Malmström Department of Surgical Sciences, Uppsala University, Uppsala, Sweden More articles by this author , Wim Van CriekingeWim Van Criekinge MDxHealth, Inc., Irvine, California Laboratory of Bioinformatics and Computational Genomics, Ghent University, Belgium More articles by this author , and Ellen C. ZwarthoffEllen C. Zwarthoff Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.09.118AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Only 3% to 28% of patients referred to the urology clinic for hematuria are diagnosed with bladder cancer. Cystoscopy leads to high diagnostic costs and a high patient burden. Therefore, to improve the selection of patients for cystoscopy and reduce costs and over testing we aimed to validate a recently developed diagnostic urine assay. Materials and Methods: Included in study were 200 patients from a total of 3 European countries who underwent cystoscopy for hematuria, including 97 with bladder cancer and 103 with nonmalignant findings. Voided urine samples were collected prior to cystoscopy. DNA was extracted and analyzed for mutations in FGFR3, TERT and HRAS, and methylation of OTX1, ONECUT2 and TWIST1. Logistic regression was used to analyze the association between predictor variables and bladder cancer. Results: Combining the methylation and mutation markers with age led to an AUC of 0.96 (95% CI 0.92–0.99) with 93% sensitivity and 86% specificity, and an optimism corrected AUC of 0.95. The AUC was higher for T1 or greater tumors compared to Ta tumors (0.99 vs 0.93). The AUC was also higher for high grade tumors compared to low grade tumors (1.00 vs 0.93). Overall negative predictive value was 99% based on the 5% to 10% prevalence of bladder cancer in patients with hematuria. This would lead to a 77% reduction in diagnostic cystoscopy. Conclusions: Analyzing hematuria patients for the risk of bladder cancer using novel molecular markers may lead to a reduction in diagnostic cystoscopy. 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Link, Google Scholar © 2017 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byvan Kessel K, de Jong J, Ziel-van der Made A, Roshani H, Haensel S, Wolterbeek J, Boevé E, Oomens E, van Casteren N, Krispin M, Boormans J, Steyerberg E, van Criekinge W and Zwarthoff E (2020) A Urine Based Genomic Assay to Triage Patients with Hematuria for CystoscopyJournal of Urology, VOL. 204, NO. 1, (50-57), Online publication date: 1-Jul-2020. Volume 197Issue 3 Part 1March 2017Page: 590-595Supplementary Materials Advertisement Copyright & Permissions© 2017 by American Urological Association Education and Research, Inc.Keywordsurinary bladder neoplasmsurinalysishematuriamethylationtumorbiomarkersMetricsAuthor Information Kim E.M. van Kessel Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands More articles by this author Willemien Beukers Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands More articles by this author Irene Lurkin Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands More articles by this author Angelique Ziel-van der Made Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands More articles by this author Kirstin A. van der Keur Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands More articles by this author Joost L. Boormans Department of Urology, Erasmus Medical Center, Rotterdam, The Netherlands More articles by this author Lars Dyrskjøt Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark More articles by this author Mirari Márquez Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre, Madrid More articles by this author Torben F. Ørntoft Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark More articles by this author Francisco X. Real Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre, Madrid Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain More articles by this author Ulrika Segersten Department of Surgical Sciences, Uppsala University, Uppsala, Sweden More articles by this author Núria Malats Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre, Madrid More articles by this author Per-Uno Malmström Department of Surgical Sciences, Uppsala University, Uppsala, Sweden More articles by this author Wim Van Criekinge MDxHealth, Inc., Irvine, California Laboratory of Bioinformatics and Computational Genomics, Ghent University, Belgium 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 ...