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J Hepatol. 2004 Dec;41(6):905-12.

Estrogen receptors in cholangiocytes and the progression of primary biliary cirrhosis.

Author information

  • 1Division of Gastroenterology, Department of Clinical Medicine, University of Rome, La Sapienza, via R. Rossellini 51, 00137 Rome, Italy. domenico.alvaro@uniroma.it

Abstract

BACKGROUND/AIMS:

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.

PMID:
15645536
[PubMed - indexed for MEDLINE]
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