title: Urinary NID2 and TWIST1 methylation to augment conventional urine cytology for the detection of bladder cancer.
abstract: BACKGROUND
  Abnormal methylation of urinary TWIST1 and NID2 conferred high sensitivity and specificity for the detection of urothelial carcinoma.
  
  
  OBJECTIVE
  We examine the performance of the urine-based TWIST1/NID2 methylation assay with the addition of urine cytology for the detection of urothelial carcinoma.
  
  
  METHODS
  A prospective multi-institutional study was conducted to assess the performance of a methylation assay for patients with hematuria or under surveillance for non-muscle invasive bladder cancer (NMIBC). All patients underwent cystoscopy, a methylation assay, and cytology. Receiver operator characteristic (ROC) curves were constructed for cytology alone, the methylation assay alone, and a combined model. Areas under the curve (AUC) were compared using likelihood ratio tests.
  
  
  RESULTS
  A total of 172 patients were enrolled (37% for hematuria and 63% NMIBC). The AUC for cytology alone with equivocal cytologies positive was 0.704, and improved to 0.773 with the addition of the DNA methylation assay (p < 0.001). When the equivocal cytologies were considered negative, the AUC improved from 0.558 to 0.697 with the addition of the DNA methylation assay (p = 0.003).
  
  
  CONCLUSIONS
  Addition of a TWIST1/NID2-based DNA methylation assay adds diagnostic value to urine cytology and the model is sensitive to the classification of equivocal cytology.
authors.affiliation: Division of Urology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Fantony
authors.affiliation: Division of Urology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Longo
authors.affiliation: Division of Urology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Ajay
authors.initials: A
authors.lastname: Gopalakrishna
authors.affiliation: Division of Urology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Richmond
authors.initials: R
authors.lastname: Owusu
authors.affiliation: Division of Urology, Urology of Virginia, Hampton, VA, USA.
authors.forename: Raymond S
authors.initials: RS
authors.lastname: Lance
authors.affiliation: Department of Pathology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Wen-Chi
authors.initials: WC
authors.lastname: Foo
authors.affiliation: Division of Urology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Brant A
authors.initials: BA
authors.lastname: Inman
authors.affiliation: Department of Urology, University of Illinois Chicago, Chicago, IL, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Abern
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000652:urine; D002135:Calcium-Binding Proteins; D002295:Carcinoma, Transitional Cell / Q000235:genetics / Q000473:pathology / Q000652:urine*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000652:urine*; D003558:Cystoscopy; D019175:DNA Methylation / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics / Q000652:urine*; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000652:urine*; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000473:pathology / Q000652:urine*
chemical_list: D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; D015815:Cell Adhesion Molecules; C114729:NID2 protein, human; D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1
keywords: Diagnostic test; epigenetic; sensitivity; smoking; specificity; urothelial carcinoma