title: Estrogen receptors in cholangiocytes and the progression of primary biliary cirrhosis.
abstract: OBJECTIVE
  Estrogen receptors (ER) in cholangiocytes of primary biliary cirrhosis (PBC) patients and their relationship with cell proliferation and death were evaluated.
  
  
  METHODS
  Liver biopsies from PBC patients with different histological stages were investigated by immunohistochemistry for ER-alpha and -beta, cytokeratin-19, proliferating cellular nuclear antigen (PCNA), Fas and terminal deoxynucleotide transferase end labelling (TUNEL). Normal livers and livers from primary sclerosing cholangitis and alcoholic cirrhosis were investigated as controls.
  
  
  RESULTS
  ER-alpha and -beta were observed in cholangiocytes of PBC patients but not in normal liver. In PBC, positivity for ER-beta was high (50-65 %) in all histological stages while, positivity for ER-alpha increased from 1% in stage I to 12 % in stage III (positivity correlated and co-localized in the same cell with PCNA). In stage IV of PBC, cholangiocytes were negative for ER-alpha in association with a lower PCNA positivity and with maximal degree of ductopenia. ER-alpha positivity in cholangiocytes of PBC patients was markedly lower than primary sclerosing cholangitis and alcoholic cirrhosis.
  
  
  CONCLUSIONS
  ER are expressed in PBC and other pathologies associated with cholangiocyte proliferation but not in normal subjects. The low expression of ER-alpha in PBC and their disappearance in the advanced histological stages suggests that an estrogenic deficiency could favour the evolution of this disease toward ductopenia.
authors.affiliation: Division of Gastroenterology, Department of Clinical Medicine, University of Rome, La Sapienza, via R. Rossellini 51, 00137 Rome, Italy. domenico.alvaro@uniroma.it
authors.forename: Domenico
authors.initials: D
authors.lastname: Alvaro
authors.forename: Pietro
authors.initials: P
authors.lastname: Invernizzi
authors.forename: Paolo
authors.initials: P
authors.lastname: Onori
authors.forename: Antonio
authors.initials: A
authors.lastname: Franchitto
authors.forename: Adriano
authors.initials: A
authors.lastname: De Santis
authors.forename: Andrea
authors.initials: A
authors.lastname: Crosignani
authors.forename: Robert
authors.initials: R
authors.lastname: Sferra
authors.forename: Stefano
authors.initials: S
authors.lastname: Ginanni-Corradini
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Mancino
authors.forename: Marco
authors.initials: M
authors.lastname: Maggioni
authors.forename: Adolf F
authors.initials: AF
authors.lastname: Attili
authors.forename: Mauro
authors.initials: M
authors.lastname: Podda
authors.forename: Eugenio
authors.initials: E
authors.lastname: Gaudio
mesh_terms: D017209:Apoptosis; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D002455:Cell Division; D015209:Cholangitis, Sclerosing / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D018450:Disease Progression; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008104:Liver Cirrhosis, Alcoholic / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008105:Liver Cirrhosis, Biliary / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism
chemical_list: D015415:Biomarkers; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D018809:Proliferating Cell Nuclear Antigen