Year: 2018
Type: article
Abstract: You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology III1 Apr 2018MP65-14 UROSEEK: A NOVEL NON-INVASIVE MOLECULAR ASSAY FOR SURVEILLANCE OF BLADDER CANCER Simeon Springer, Maria Del Carmen Rodriguez Pena, Aline Tregnago, Diana Taheri, Stephania Bezerra, Isabela Cunha, Kazutoshi Fujita, Dilek Baydar, Trinity Bivalacqua, Nickolas Papadopoulos, Kenneth W Kinzler, Bert Vogelstein, and George Netto Simeon SpringerSimeon Springer More articles by this author , Maria Del Carmen Rodriguez PenaMaria Del Carmen Rodriguez Pena More articles by this author , Aline TregnagoAline Tregnago More articles by this author , Diana TaheriDiana Taheri More articles by this author , Stephania BezerraStephania Bezerra More articles by this author , Isabela CunhaIsabela Cunha More articles by this author , Kazutoshi FujitaKazutoshi Fujita More articles by this author , Dilek BaydarDilek Baydar More articles by this author , Trinity BivalacquaTrinity Bivalacqua More articles by this author , Nickolas PapadopoulosNickolas Papadopoulos More articles by this author , Kenneth W KinzlerKenneth W Kinzler More articles by this author , Bert VogelsteinBert Vogelstein More articles by this author , and George NettoGeorge Netto More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.2080AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Current non-invasive approaches for bladder cancer (BC) detection are suboptimal. In this study, we report the development of a non-invasive molecular assay (UroSEEK) for detection of BC recurrence during disease surveillance using DNA recovered from cells shed into urine. UroSEEK incorporates assays for mutations in 11 genes and copy number changes on 39 chromosome arms. METHODS Urine samples were collected prospectively from patients with previously established diagnosis of BC from two institutions. Patients with a known history of malignancy other than BC were excluded. Urine samples were analyzed for mutation in three component assays: First, a multiplex PCR was used to detect mutations in regions of CDKN2A, ERBB2, FGFR3, HRAS, KRAS, MET, MLL, PIK3CA, TP53, and VHL. Second, an amplification primer was used to amplify a 73-bp segment containing the region of the TERT promoter. Aneuploidy was assessed with FastSeqS, which uses a single primer pair to amplify ˜38,000 loci scattered throughout the genome. Follow up data was obtained from medical records. RESULTS 322 patients were identified, 187 had biopsy proven recurrence. The multiplex PCR assay detected mutations in 52% patients that developed recurrent BC. The most commonly altered genes were TP53 and FGFR3 (38% and 29% of the 200 mutations; respectively). Mutations in TERT promoter were detected in 57% of samples and aneuploidy was detected in 28% of samples from patients with recurrent disease. The most commonly altered chromosomal arms were 8p, 8q, and 9p. In patients with BC recurrence, 127/187 samples were positive for at least one of the three UroSEEK componont assays for a sensitivity of 68% and a specificity of 80%.In combination with cytology UroSEEK demonstrated 71% sensitivity and 82% specificity. One-hundred patients had “atypical” diagnosis on cytology. Among the latter, UroSEEK was positive in 68% of 71 patients that recurred with a 83% specificity and a mean lead time from biopsy proven recurrence of 6 months (range 0 - 35).Cytology did not detect recurrent low-grade tumors while UroSEEK detected 67% of them. Cytology detected 41% of high-grade tumors while UroSEEK detected 71%. CONCLUSIONS UroSEEK raised the sensitivity of cytology from 25% to 71% and detected recurrence in 68% of atypical cytology patients. UroSEEK positivity preceded clinical diagnosis by months to years. Prospective trials are required to demonstrate the ability of UroSEEK to improve outcome in BC surveillance. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e864 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Simeon Springer More articles by this author Maria Del Carmen Rodriguez Pena More articles by this author Aline Tregnago More articles by this author Diana Taheri More articles by this author Stephania Bezerra More articles by this author Isabela Cunha More articles by this author Kazutoshi Fujita More articles by this author Dilek Baydar More articles by this author Trinity Bivalacqua More articles by this author Nickolas Papadopoulos More articles by this author Kenneth W Kinzler More articles by this author Bert Vogelstein More articles by this author George Netto More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...
Source: The Journal of Urology
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2795649586