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• W1973178538 abstract "You have accessJournal of UrologyBladder Cancer: Metastatic Disease + Staging1 Apr 20131875 METHYLATION OF TUMOR SUPPRESSOR GENES PREDICT RECURRENCE AND SUBCLASSIFY NON MUSCLE-INVASIVE DISEASE: PTA LOW GRADE VERSUS PT1 LOW GRADE AND PT1 HIGH GRADE BLADDER TUMORS Raquel Sacristan, Carolina Gonzalez, Jesus Fernandez-Gomez, Florentino Fresno, Safwan Escaf, and Marta Sanchez-Carbayo Raquel SacristanRaquel Sacristan Madrid, Spain More articles by this author , Carolina GonzalezCarolina Gonzalez Madrid, Spain More articles by this author , Jesus Fernandez-GomezJesus Fernandez-Gomez Oviedo, Spain More articles by this author , Florentino FresnoFlorentino Fresno Oviedo, Spain More articles by this author , Safwan EscafSafwan Escaf Jove, Spain More articles by this author , and Marta Sanchez-CarbayoMarta Sanchez-Carbayo Madrid, Spain More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.2294AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Genetic and epigenetic factors are involved in tumorigenesis and bladder cancer progression. The role of epigenetic factors at distinguishing pathological and clinical subgroups is not well defined. We aimed at evaluating the role of methylation of 25 tumor suppressor genes (TSG) to subclassify non-muscle invasive (NMI) bladder tumor subtypes and as clinical outcome prognosticators. METHODS A retrospective design included paraffin-embedded tumors (n=251) of patients with primary NMI disease: pTa Low Grade (LG)(n=79), PT1LG(n=81), and PT1 High Grade (HG) (n=91). Methylation of 25 TSG was measured using a methylation-specific multiplex ligation-dependent probe amplification assay (MS-MLPA). Recurrence, progression into muscle invasive tumors and disease-specific survival (DSS) rates were analyzed using competing risks regression analysis. RESULTS The TSGs most frequently methylated in the overall series were STK11 (96.8%), MGMT2 (64.5%), RARB (63.0%) and GATA5 (63.0%). TSGs methylation significantly correlated to clinicopathological variables within each specific subgroup and the overall series. Methylation of RARB (p=0.027), CD44 (p=0.002), PAX5A (p=0.018), GSTP1 (p<0.001), IGSF4 (p<0.001), PYCARD (p<0.001), CDH13 (p=0.028), TP53 (p=0.001) and GATA5 (p=0.001) allowed classification of PTa versus PT1 tumors while RARB (p<0.001), CD44 (p<0.001), GSTP1 (p<0.001), IGSF4 (p=0.005), CHFR (p=0.032), PYCARD (p<0.001), TP53 (p<0.001), STK11 (p=0.028) and GATA5 (p<0.001) distinguished LG vs HG tumors. Multivariate analyses indicated that PAX5A (p=0.019), WT1 (p=0.042) and BRCA1 (p=0.023) methylation independently predicted recurrence in pTaLG lesions, PAX6 (p=0.044), ATM (p=0.004), CHFR (p=0.035) and RB1 (p=0.007) in pT1LG tumors, and PYCARD (p=0.035) in pT1HG disease, and PAX5A (p=0.01) and RB1 (p=0.008) in the overall NMI series. CONCLUSIONS Methylation of TSG distinguished NMI bladder tumors depending on their clinicopathological phenotypes. Methylation of TSG correlated to patient outcome and behaved as independent prognosticators of recurrence. Methylation of TSG may select NMI patients who may require closer surveillance and more aggressive therapeutic interventions. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e769 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Raquel Sacristan Madrid, Spain More articles by this author Carolina Gonzalez Madrid, Spain More articles by this author Jesus Fernandez-Gomez Oviedo, Spain More articles by this author Florentino Fresno Oviedo, Spain More articles by this author Safwan Escaf Jove, Spain More articles by this author Marta Sanchez-Carbayo Madrid, Spain More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ..." @default.
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• W1973178538 title "1875 METHYLATION OF TUMOR SUPPRESSOR GENES PREDICT RECURRENCE AND SUBCLASSIFY NON MUSCLE-INVASIVE DISEASE: PTA LOW GRADE VERSUS PT1 LOW GRADE AND PT1 HIGH GRADE BLADDER TUMORS" @default.
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