MP7-10 THE PROGNOSTIC IMPACT OF HISTONE H3K27 TRIMETHYLATION REGULATED BY EZH2 IN PATIENTS WITH UPPER URINARY TRACT UROTHELIAL CARCINOMA

Abstract

You have accessJournal of UrologyBladder Cancer: Upper Tract TCC II1 Apr 2015MP7-10 THE PROGNOSTIC IMPACT OF HISTONE H3K27 TRIMETHYLATION REGULATED BY EZH2 IN PATIENTS WITH UPPER URINARY TRACT UROTHELIAL CARCINOMA Yasumasa Miyazaki, Takeo Kosaka, Shuji Mikami, Eiji Kikuchi, Nobuyuki Tanaka, Yota Yasumizu, Akira Miyajima, Yasunori Okada, and Mototsugu Oya Yasumasa MiyazakiYasumasa Miyazaki More articles by this author , Takeo KosakaTakeo Kosaka More articles by this author , Shuji MikamiShuji Mikami More articles by this author , Eiji KikuchiEiji Kikuchi More articles by this author , Nobuyuki TanakaNobuyuki Tanaka More articles by this author , Yota YasumizuYota Yasumizu More articles by this author , Akira MiyajimaAkira Miyajima More articles by this author , Yasunori OkadaYasunori Okada More articles by this author , and Mototsugu OyaMototsugu Oya More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.217AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Enhancer of zeste homolog 2 (EZH2), a histone methyltransferase regulating epigenetic modifications, is overexpressed in various carcinomas and is associated with clinicopathological characteristics and biological behavior. Although EZH2 regulates the trimethylation of lysine 27 on histone H3 (H3K27me3) and epigenetic process in carcinogenesis, it has not been fully characterized yet that these status reflects the activity or the predictor of cancer progression. The aim of this study was to address the prognostic value of EZH2 and H3K27me3 in upper urinary tract urothelial carcinomas (UTUC). METHODS We retrospectively analyzed the clinical records of 173 patients with UTUC (Ta-4N0M0) treated by radical nephroureterectomy (RNU). The median follow-up period was 3.3 years. We immunohistochemically examined the expression of EZH2 and H3K27me3 in tumor cells. The immunohistochemical stain was evaluated by a semi-quantitative assessment including both the intensity of staining and the percentage of positive cells. Then, we analyzed the association between the score and clinical outcomes. RESULTS Thirty-six patients experienced tumor recurrence, and of these 30 died of the disease during follow-up. The expression of EZH2 was observed strongly in the tumor cells and was negative in normal tissue. The methylation of H3K27me3 was observed in all cells of the tissue however was especially strong in tumor cells. The score of EZH2 and H3K27me3 was significantly associated with tumor grade, pathological T stage, and lymphovascular invasion (LVI). Using Spearman's correlation coefficient test, we detected a significant positive correlation between the score of EZH2 and H3K27me3 in the tumor (ρ = 0.414, P < 0.001). The 5-year recurrence-free and cancer-specific survival rates were 59.9% and 65.9% in patients with high EZH2, and 89.5% and 93.3% in their counterparts, respectively (P < 0.001). The 5-year recurrence-free and cancer-specific survival rates were 62.9% and 69.2% in patients with high H3K27me3, and 87.7% and 91.4% in their counterparts, respectively (P < 0.001). Multivariate analyses revealed that high H3K27me3 was an independent prognostic indicator of both tumor recurrence (P = 0.009, HR = 2.77) and cancer-specific survival (P = 0.004, HR = 3.78). CONCLUSIONS These results suggest that epigenetic modifications of H3K27me3 by EZH2 could provide additional prognostic information in patients with UTUC treated by RNU. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e67 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yasumasa Miyazaki More articles by this author Takeo Kosaka More articles by this author Shuji Mikami More articles by this author Eiji Kikuchi More articles by this author Nobuyuki Tanaka More articles by this author Yota Yasumizu More articles by this author Akira Miyajima More articles by this author Yasunori Okada More articles by this author Mototsugu Oya More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...