Estrogen receptors in cholangiocytes and the progression of primary biliary cirrhosis.
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.
Alvaro
Domenico
D
Division of Gastroenterology, Department of Clinical Medicine, University of Rome, La Sapienza, via R. Rossellini 51, 00137 Rome, Italy. domenico.alvaro@uniroma.it
Invernizzi
Pietro
P
Onori
Paolo
P
Franchitto
Antonio
A
De Santis
Adriano
A
Crosignani
Andrea
A
Sferra
Robert
R
Ginanni-Corradini
Stefano
S
Mancino
Maria Grazia
MG
Maggioni
Marco
M
Attili
Adolf F
AF
Podda
Mauro
M
Gaudio
Eugenio
E
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
D015415:Biomarkers; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D018809:Proliferating Cell Nuclear Antigen