MP01-09 CAN A GENE METHYLATION ASSAY IMPROVE THE PERFORMANCE OF CYTOLOGY?

Abstract

You have accessJournal of UrologyBladder Cancer: Epidemiology & Evaluation I1 Apr 2016MP01-09 CAN A GENE METHYLATION ASSAY IMPROVE THE PERFORMANCE OF CYTOLOGY? Thomas Longo, Ajay Gopalakrishna, Joseph Fantony, Richmond Owusu, Raymond Lance, Wen-Chi Foo, Brant Inman, and Michael Abern Thomas LongoThomas Longo More articles by this author , Ajay GopalakrishnaAjay Gopalakrishna More articles by this author , Joseph FantonyJoseph Fantony More articles by this author , Richmond OwusuRichmond Owusu More articles by this author , Raymond LanceRaymond Lance More articles by this author , Wen-Chi FooWen-Chi Foo More articles by this author , Brant InmanBrant Inman More articles by this author , and Michael AbernMichael Abern More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1839AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Detection and surveillance of bladder cancer is a physical, financial, and psychological stress on the patient. Cytology is well established, but has suboptimal performance. Medicine has moved beyond single tests to panels of biomarkers. We have looked at two novel markers, TWIST1 and NID2, using gene methylation. Using data from our clinical trial, we have tried to improve urine cytology by combining it with our panel. METHODS After IRB approval, we conducted a multi-institutional prospective trial of subjects undergoing initial hematuria evaluation or surveillance for bladder cancer (9/2008-12/2010). Subjects underwent standard cystoscopy to determine the presence or absence of a bladder tumor. A voided urine specimen was also collected for the DNA methylation assay and for voided urine cytology. Specimens were blinded and processed at a central lab. Genomic DNA was isolated and analysis done with real-time methylation-specific PCR using specific primers and probes for NID2, TWIST1, and β-actin. Gene copy numbers of methylated NID2 and TWIST1 were later dichotomized as a methylated (TWIST1 ≥ 37 or NID2 ≥ 21) or not methylated. An assay was considered adequate if each sample had at least 10 copies of the β-actin gene isolated from the urine. Receiver operating characteristic curves were constructed and areas under the curve were calculated for cytology, the methylation assay, and the combination of cytology with the methylation assay. RESULTS Originally 222 subjects were tested with the assay, but 13 were inadequate samples, and 37 were missing a cystoscopy or cytology. Overall, 37% of subjects were undergoing a hematuria workup and 63% were on surveillance for NMIBC. Approximately 75% were male with the majority of prior cancers were Ta low-grade. The sensitivity and specificity for the methylation assay were 57% and 72% respectively. Interestingly, the methylation assay performed better in subjects with hematuria than in subjects undergoing NMIBC surveillance (sensitivity 74% versus 48%, specificity 81% versus 63%). The separate AUC for the methylation assay was calculated as 0.669. With the addition of the assay, the AUC for cytology increased from 0.704 to 0.773 (p < 0.01). CONCLUSIONS DNA methylation has shown promise as a tool for screening and surveillance. Our multi-institutional study has validated the methodology of this novel test. It suggests that it is applicable as an adjunct to cytology and offers a clinically meaningful improvement. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e4 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Thomas Longo More articles by this author Ajay Gopalakrishna More articles by this author Joseph Fantony More articles by this author Richmond Owusu More articles by this author Raymond Lance More articles by this author Wen-Chi Foo More articles by this author Brant Inman More articles by this author Michael Abern More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...