title: Expression of Estrogen Receptor Beta Predicts Oncologic Outcome of pT3 Upper Urinary Tract Urothelial Carcinoma Better Than Aggressive Pathological Features.
abstract: Upper urinary tract urothelial carcinoma (UT-UC) is rare and treatment options or prognostic markers are limited. There is increasing evidence indicating that urothelial carcinoma may be an endocrine-related cancer. The aim of this study was to analyze the prognostic effect of estrogen receptor beta (ERβ) on the outcome of UT-UC. From 2005 to 2012, this study included 105 patients with pT3 UT-UC. Perioperative factors, pathological features, and ERβ immunostaining were reviewed and prognostic effects were examined by multivariate analysis. This study divided patients into either the ERβ-high (n = 52) or ERβ-low (n = 53) group and analyzed their oncologic outcomes. All pathological features except infiltrating tumor architecture (significantly higher incidence in ERβ-low group, p = 0.004) are symmetric in both groups. Low ERβ expression was significantly correlated with local recurrence and distant metastasis in univariate analysis (p = 0.035 and 0.004, respectively) and multivariate analysis (p = 0.05 and 0.008, respectively). Cell line study also proved that knock down of ERβ cause less UTUC proliferation and migration. In addition, ERβ agonist also enhanced the cytotoxic and migration inhibition effect of cisplatin and ERβ antagonist cause the UTUC cell more resistant to cisplatin. This result may help identify patients in need of adjuvant therapy or develop potential targeted therapy.
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Urology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Hao Lun
authors.initials: HL
authors.lastname: Luo
authors.affiliation: Department of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Ming Tse
authors.initials: MT
authors.lastname: Sung
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.|Center for Research Resources and Development, Kaohsiung Medical University, Kaohsiung City, Taiwan.
authors.forename: Eing Mei
authors.initials: EM
authors.lastname: Tsai
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan.
authors.forename: Chang Shen
authors.initials: CS
authors.lastname: Lin
authors.affiliation: Department of Urology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Nai Lun
authors.initials: NL
authors.lastname: Lee
authors.affiliation: Department of Urology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.|Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan.
authors.forename: Yueh-Hua
authors.initials: YH
authors.lastname: Chung
authors.affiliation: Department of Urology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Po Hui
authors.initials: PH
authors.lastname: Chiang
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D002295:Carcinoma, Transitional Cell / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology; D020847:Estrogen Receptor Modulators / Q000494:pharmacology; D047629:Estrogen Receptor beta / Q000819:agonists / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D009570:Nitriles / Q000494:pharmacology; D011379:Prognosis; D011422:Propionates / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D034622:RNA Interference; D012189:Retrospective Studies; D014551:Urinary Tract / Q000378:metabolism* / Q000473:pathology
chemical_list: C486182:2,3-bis(4-hydroxyphenyl)-propionitrile; C556295:4-(2-phenyl-5,7-bis(trifluoromethyl)pyrazolo(1,5-a)pyrimidin-3-yl)phenol; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D020847:Estrogen Receptor Modulators; D047629:Estrogen Receptor beta; D009570:Nitriles; D011422:Propionates; D011720:Pyrazoles; D011743:Pyrimidines; D002945:Cisplatin