title: Prostate Cancer Expression Profiles of Cytoplasmic ERβ1 and Nuclear ERβ2 are Associated with Poor Outcomes following Radical Prostatectomy.
abstract: Existing data regarding the expression of estrogen receptors (ERs) and prostate cancer outcomes have been limited. We evaluated the relationship of expression profiles of ERβ subtypes and the ER GPR30 (G-protein-coupled receptor-30) with patient factors at diagnosis and outcomes following radical prostatectomy.
  
  
  
  Tissue microarrays constructed using samples from 566 men with long-term clinical followup were analyzed by immunohistochemistry targeting ERβ1, ERβ2, ERβ5 and GPR30. An experienced pathologist scored receptor distribution and staining intensity. Tumor staining characteristics were evaluated for associations with patient characteristics, recurrence-free survival and prostate cancer specific mortality following radical prostatectomy.
  
  
  
  Prostate cancer cells had unique receptor subtype staining patterns. ERβ1 demonstrated predominantly nuclear localization while ERβ2, ERβ5 and GPR30 were predominantly cytoplasmic. After controlling for patient factors intense cytoplasmic ERβ1 staining was independently associated with time to recurrence (HR 1.7, 95% CI 1.1-2.6, p = 0.01) and prostate cancer specific mortality (HR 6.6, 95% CI 1.8-24.9, p = 0.01). Intense nuclear ERβ2 staining was similarly independently associated with prostate cancer specific mortality (HR 3.9, 95% CI 1.1-13.4, p = 0.03). Patients with cytoplasmic ERβ1 and nuclear ERβ2 co-staining had significantly worse 15-year prostate cancer specific mortality than patients with expression of only cytoplasmic ERβ1, only nuclear ERβ2 and neither ER (16.4%, 4.3%, 0.0% and 2.0 %, respectively, p = 0.001).
  
  
  
  Increased cytoplasmic ERβ1 and nuclear ERβ2 expression is associated with worse cancer specific outcomes following radical prostatectomy. These findings suggest that tumor ERβ1 and ERβ2 staining patterns provide prognostic information on patients treated with radical prostatectomy.
authors.affiliation: Department of Urology, School of Medicine, University of Washington, Seattle, Washington. Electronic address: grschade@uw.edu.
authors.forename: George R
authors.initials: GR
authors.lastname: Schade
authors.affiliation: Department of Urology, School of Medicine, University of Washington, Seattle, Washington.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Holt
authors.affiliation: Department of Urology, School of Medicine, University of Washington, Seattle, Washington.
authors.forename: Xiaotun
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Division of Environmental Genetics and Molecular Toxicology, University of Cincinnati College of Medicine, Cincinnati Cancer Institute, Cincinnati, Ohio.
authors.forename: Dan
authors.initials: D
authors.lastname: Song
authors.affiliation: Department of Urology, School of Medicine, University of Washington, Seattle, Washington; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Wright
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Kolb
authors.affiliation: Department of Urology, School of Medicine, University of Washington, Seattle, Washington.
authors.forename: Hung-Ming
authors.initials: HM
authors.lastname: Lam
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Linda
authors.initials: L
authors.lastname: Levin
authors.affiliation: Center for Environmental Genetics and Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati Cancer Institute, Cincinnati, Ohio.
authors.forename: Yuet-Kin
authors.initials: YK
authors.lastname: Leung
authors.affiliation: Division of Environmental Genetics and Molecular Toxicology, University of Cincinnati College of Medicine, Cincinnati Cancer Institute, Cincinnati, Ohio; Center for Environmental Genetics and Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati Cancer Institute, Cincinnati, Ohio.
authors.forename: Shuk-Mei
authors.initials: SM
authors.lastname: Ho
authors.affiliation: Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Janet L
authors.initials: JL
authors.lastname: Stanford
mesh_terms: D000328:Adult; D000368:Aged; D047629:Estrogen Receptor beta / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism; D011379:Prognosis; D011467:Prostate / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D011468:Prostatectomy / Q000009:adverse effects / Q000379:methods*; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000601:surgery; D011960:Receptors, Estrogen / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D012189:Retrospective Studies; D016019:Survival Analysis; D046888:Tissue Array Analysis
chemical_list: D047629:Estrogen Receptor beta; C109584:GPER1 protein, human; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled
keywords: prognosis; prostatectomy; prostatic neoplasms; receptors, estrogen; tissue array analysis