Estrogen receptors in cholangiocytes and the progression of primary biliary cirrhosis

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-a and -b, 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-a and -b were observed in cholangiocytes of PBC patients but not in normal liver. In PBC, positivity for ER-b was high (50–65%) in all histological stages while, positivity for ER-a 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-a in association with a lower PCNA positivity and with maximal degree of ductopenia. ER-a 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-a in PBC and their disappearance in the advanced histological stages suggests that an estrogenic deficiency could favour the evolution of this disease toward ductopenia.