MP71-06 PROGNOSTIC SIGNIFICANCE OF EZH2 EXPRESSION IN UPPER TRACT UROTHELIAL CARCINOMA

Abstract

You have accessJournal of UrologyBladder Cancer: Upper Tract Transitional Cell Carcinoma I1 Apr 2017MP71-06 PROGNOSTIC SIGNIFICANCE OF EZH2 EXPRESSION IN UPPER TRACT UROTHELIAL CARCINOMA Ahmet Aydin, Nirmish Singla, Vandana Panwar, Ryan Hutchinson, Solomon Woldu, Christopher Wood, Jose Karam, Alon Weizer, Jay Raman, Mesut Remzi, Nathalie Rioux-Leclercq, Andrea Haitel, Marco Roscigno, Christian Bolenz, Karim Bensalah, Arthur Sagalowsky, Shahrokh Shariat, Yair Lotan, Aditya Bagrodia, Payal Kapur, Vitaly Margulis, and Laura-Maria Krabbe Ahmet AydinAhmet Aydin More articles by this author , Nirmish SinglaNirmish Singla More articles by this author , Vandana PanwarVandana Panwar More articles by this author , Ryan HutchinsonRyan Hutchinson More articles by this author , Solomon WolduSolomon Woldu More articles by this author , Christopher WoodChristopher Wood More articles by this author , Jose KaramJose Karam More articles by this author , Alon WeizerAlon Weizer More articles by this author , Jay RamanJay Raman More articles by this author , Mesut RemziMesut Remzi More articles by this author , Nathalie Rioux-LeclercqNathalie Rioux-Leclercq More articles by this author , Andrea HaitelAndrea Haitel More articles by this author , Marco RoscignoMarco Roscigno More articles by this author , Christian BolenzChristian Bolenz More articles by this author , Karim BensalahKarim Bensalah More articles by this author , Arthur SagalowskyArthur Sagalowsky More articles by this author , Shahrokh ShariatShahrokh Shariat More articles by this author , Yair LotanYair Lotan More articles by this author , Aditya BagrodiaAditya Bagrodia More articles by this author , Payal KapurPayal Kapur More articles by this author , Vitaly MargulisVitaly Margulis More articles by this author , and Laura-Maria KrabbeLaura-Maria Krabbe More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2262AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Enhancer of zeste homolog 2 is a methyltransferase encoded by the EZH2 gene. The role of EZH2 upregulation has been studied in several malignancies, including bladder cancer, though its role in upper tract urothelial carcinoma (UTUC) is poorly understood. We sought to evaluate the prognostic value of EZH2 expression in UTUC. METHODS We reviewed a multi-institutional cohort of patients who underwent radical nephroureterectomy (RNU) for high-grade UTUC from 1990-2008. Immunohistochemistry for EZH2 was performed on tissue microarrays from RNU specimens. The percentage of staining was evaluated, with EZH2 positivity defined as >20% staining present. Clinicopathologic characteristics and oncologic outcomes including recurrence-free (RFS), cancer-specific (CSS), and overall survival (OS) were compared between patients stratified by EZH2 positivity. Prognostic role of EZH2 was assessed using Kaplan-Meier (KM) analysis. Predictors of oncologic outcomes were identified using univariate (UVA) and multivariate (MVA) Cox regression analysis. Significance was defined for p<0.05. RESULTS 402 patients were included for analysis, with median follow-up 35.5 months. 313 (77.9%) patients were EZH2-negative and 89 (22.1%) were EZH2-positive. While gender, pT stage, pN stage, and prior bladder cancer were similar between groups, EZH2 expression was more often associated with ureteral location, sessile architecture, necrosis, and CIS (Table). On UVA, EZH2 was a significant predictor for worse RFS (HR 1.63, p=0.019), CSS (HR 1.87, p=0.004), and OS (HR 1.97, p<0.001). On MVA adjusted for age, pT, pN, and LVI, EZH2 remained a significant predictor for worse OS (HR 1.65, p=0.005), while significance was lost for RFS and CSS. KM curves are shown (Figure). CONCLUSIONS EZH2 expression appears to be associated with adverse pathologic features and may predict worse oncologic outcomes in patients with high-grade UTUC. The role of EZH2 pathways in UTUC pathogenesis remains to be further elucidated. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e947 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Ahmet Aydin More articles by this author Nirmish Singla More articles by this author Vandana Panwar More articles by this author Ryan Hutchinson More articles by this author Solomon Woldu More articles by this author Christopher Wood More articles by this author Jose Karam More articles by this author Alon Weizer More articles by this author Jay Raman More articles by this author Mesut Remzi More articles by this author Nathalie Rioux-Leclercq More articles by this author Andrea Haitel More articles by this author Marco Roscigno More articles by this author Christian Bolenz More articles by this author Karim Bensalah More articles by this author Arthur Sagalowsky More articles by this author Shahrokh Shariat More articles by this author Yair Lotan More articles by this author Aditya Bagrodia More articles by this author Payal Kapur More articles by this author Vitaly Margulis More articles by this author Laura-Maria Krabbe More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...