title: Differential expression of the estrogen receptor beta (ERbeta) in human prostate tissue, premalignant changes, and in primary, metastatic, and recurrent prostatic adenocarcinoma.
abstract: BACKGROUND
  Estrogen signaling mediated by the estrogen receptor beta (ERbeta) has potential implications in normal and abnormal prostate growth. Few studies have addressed this issue in human prostate tissue leaving conflicting results on the immunolocalization of the ERbeta in benign and neoplastic lesions.
  
  
  METHODS
  Using a new monoclonal antibody, the current study reports on the differential expression of the ERbeta in tissue sections from 132 patients with prostate cancer.
  
  
  RESULTS
  The prostatic epithelium expressed the ERbeta extensively in secretory luminal cell types and at lower levels in basal cells. Atrophic changes of the peripheral zone (PZ) were more immunoreactive than hyperplastic lesions of the transition zone (TZ). When compared with glandular tissue of the PZ, high-grade prostatic intraepithelial neoplasia (HGPIN) revealed decreased levels of the ERbeta in 30 of 47 cases and was unreactive in six lesions. In informative cases with suitable internal controls, all primary tumors (n = 60), lymph node (n = 7), and bone metastases (n = 5) expressed the ERbeta at variable degree. No correlation was found between the ERbeta status, the primary Gleason grade (P = 0.254), and the pathological stage (P = 0.157). Recurrent adenocarcinoma revealed markedly decreased levels in 15 of 40 cases and was ERbeta negative in five recurrent lesions.
  
  
  CONCLUSIONS
  The secretory epithelium is a major target of ERbeta-mediated estrogen signaling in the human prostate. Its downregulation in HGPIN is consistent with chemopreventive effects that the ERbeta may exert on the prostatic epithelium. The continuous expression of the receptor protein at significant levels in untreated primary and metastatic adenocarcinoma indicates that these tumors can use estrogens through an ERbeta-mediated pathway. The partial loss of the ERbeta in recurrent tumors after androgen-deprivation may reflect the androgen-dependence of ERbeta gene expression in human prostate cancer.
authors.affiliation: Institute of Pathology, University of the Saarland, Homburg-Saar, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Fixemer
authors.forename: Klaus
authors.initials: K
authors.lastname: Remberger
authors.forename: Helmut
authors.initials: H
authors.lastname: Bonkhoff
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000911:Antibodies, Monoclonal; D018890:Chemoprevention; D015536:Down-Regulation; D004848:Epithelium; D047629:Estrogen Receptor beta; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009362:Neoplasm Metastasis / Q000473:pathology*; D009364:Neoplasm Recurrence, Local; D011230:Precancerous Conditions / Q000473:pathology; D011467:Prostate / Q000502:physiology*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D011960:Receptors, Estrogen / Q000096:biosynthesis*; D015398:Signal Transduction
chemical_list: D000911:Antibodies, Monoclonal; D047629:Estrogen Receptor beta; D011960:Receptors, Estrogen