632 BUBR1 OVEREXPRESSION MAY PREDICT DISEASE-SPECIFIC SURVIVAL AFTER NEPHROURETERECTOMY IN UPPER URINARY TRACT UROTHELIAL CARCINOMA

Abstract

You have accessJournal of UrologyUrothelial Cancer: Upper Tract Tumors1 Apr 2012632 BUBR1 OVEREXPRESSION MAY PREDICT DISEASE-SPECIFIC SURVIVAL AFTER NEPHROURETERECTOMY IN UPPER URINARY TRACT UROTHELIAL CARCINOMA Yoshiaki Yamamoto, Jun Nishigima, Yoshihiro Miyachika, Yoshihisa Kawai, Hiroaki Matsumoto, Kazuhiro Nagao, Takahiko Hara, Shigeru Sakano, Kohsuke Sasaki, and Hideyasu Matsuyama Yoshiaki YamamotoYoshiaki Yamamoto Ube, Japan More articles by this author , Jun NishigimaJun Nishigima Ube, Japan More articles by this author , Yoshihiro MiyachikaYoshihiro Miyachika Ube, Japan More articles by this author , Yoshihisa KawaiYoshihisa Kawai Ube, Japan More articles by this author , Hiroaki MatsumotoHiroaki Matsumoto Ube, Japan More articles by this author , Kazuhiro NagaoKazuhiro Nagao Ube, Japan More articles by this author , Takahiko HaraTakahiko Hara Ube, Japan More articles by this author , Shigeru SakanoShigeru Sakano Ube, Japan More articles by this author , Kohsuke SasakiKohsuke Sasaki Ube, Japan More articles by this author , and Hideyasu MatsuyamaHideyasu Matsuyama Ube, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.711AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES There are few reliable markers to distinguish tumors with aggressive characteristics from others in upper urinary tract urothelial carcinoma (UUTUC). The purpose of this study was to identity a biomarker related to genetic instability (chromosomal instability or microsatellite instability) that allows for the prediction of prognosis for UUTUC. METHODS Expression of BUBR1, p53, polo-like kinase 1 (PLK1), MLH1 and MSH2 proteins were immunohistochemically assessed in 102 patients who had nephroureterectomy for UUTUC. Numerical aberrations of chromosomes 7, 9 and 17 were evaluated by fluorescence in situ hybridization which allowed for the estimation of the degree of chromosomal instability. Relationship between BUBR1 expression and the BUB1B copy number gain, the gene encoding BUBR1, was examined by array-based comparative genomic hybridization (CGH) in 32 patients with UUTUC. The clinical records were reviewed retrospectively and the mean follow-up was 46.6 months. RESULTS Overexpression of BUBR1, p53 and PLK1 were detected in 41 of 102 (40.2%), 52 of 101 (51.5%), and 27 of 102 (26.5%) of tumors, respectively. MLH1 and MSH2 protein expression decreased in 32 of 101 (31.7%) and 21 of 101 (20.8%) tumors, respectively. Overexpression of BUBR1 significantly correlated with higher histological grade, advanced pathological stage, lymph node metastasis and chromosomal instability (P < 0.0001, 0.0024, 0.0063 and 0.0060, respectively). Array CGH revealed that no tumors (0%) showed BUB1B amplification and gain, indicating that the overexpression of BUBR1 in these UUTUC was independent of BUB1B copy number gain. Univariate analyses showed that BUBR1, pT stage, pN stage and MSH2 were significantly related to disease-specific survival (P = 0.0008, 0.0061, 0.0146 and 0.0329, respectively). Multivariate analysis using the Cox proportional hazard model showed that BUBR1 overexpression was the only prognostic factor with independent significance for disease-specific survival (hazard ratio, 3.35; 95% confidence interval, 1.13-11.33; P = 0.0289). CONCLUSIONS These data suggest that overexpression of BUBR1 may have great potential as a biomarker for estimating disease-specific survival in patients with UUTUC treated by nephroureterectomy. The BUBR1 status could be useful for selecting patients and determining the efficacy of adjuvant therapy strategies. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e257 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yoshiaki Yamamoto Ube, Japan More articles by this author Jun Nishigima Ube, Japan More articles by this author Yoshihiro Miyachika Ube, Japan More articles by this author Yoshihisa Kawai Ube, Japan More articles by this author Hiroaki Matsumoto Ube, Japan More articles by this author Kazuhiro Nagao Ube, Japan More articles by this author Takahiko Hara Ube, Japan More articles by this author Shigeru Sakano Ube, Japan More articles by this author Kohsuke Sasaki Ube, Japan More articles by this author Hideyasu Matsuyama Ube, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...