Estrogen receptors in cholangiocytes and the progression of primary biliary cirrhosis

• Published in: Journal of hepatology 2004-12, Vol.41 (6), p.905-912
• Main Authors: Alvaro, Domenico, Invernizzi, Pietro, Onori, Paolo, Franchitto, Antonio, De Santis, Adriano, Crosignani, Andrea, Sferra, Roberta, Ginanni-Corradini, Stefano, Grazia Mancino, Maria, Maggioni, Marco, Attili, Adolfo F., Podda, Mauro, Gaudio, Eugenio
• Format: Article
• Language: English
• Subjects: Apoptosis; Bile Ducts, Intrahepatic - metabolism; Bile Ducts, Intrahepatic - pathology; Biological and medical sciences; Biomarkers - metabolism; Case-Control Studies; Cell Division; Cholangitis, Sclerosing - metabolism; Cholangitis, Sclerosing - pathology; Cholangitis, Sclerosing - physiopathology; Disease Progression; Estrogen Receptor alpha - metabolism; Estrogen Receptor beta - metabolism; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Immunohistochemistry; Liver - metabolism; Liver - pathology; Liver Cirrhosis, Alcoholic - metabolism; Liver Cirrhosis, Alcoholic - pathology; Liver Cirrhosis, Alcoholic - physiopathology; Liver Cirrhosis, Biliary - metabolism; Liver Cirrhosis, Biliary - pathology; Liver Cirrhosis, Biliary - physiopathology; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Medical sciences; Other diseases. Semiology; Proliferating Cell Nuclear Antigen - metabolism
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/j.jhep.2004.08.022

Estrogen receptors (ER) in cholangiocytes of primary biliary cirrhosis (PBC) patients and their relationship with cell proliferation and death were evaluated. Liver biopsies from PBC patients with different histological stages were investigated by immunohistochemistry for ER-α and -β, 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. ER-α and -β were observed in cholangiocytes of PBC patients but not in normal liver. In PBC, positivity for ER-β was high (50–65%) in all histological stages while, positivity for ER-α 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-α in association with a lower PCNA positivity and with maximal degree of ductopenia. ER-α positivity in cholangiocytes of PBC patients was markedly lower than primary sclerosing cholangitis and alcoholic cirrhosis. ER are expressed in PBC and other pathologies associated with cholangiocyte proliferation but not in normal subjects. The low expression of ER-α in PBC and their disappearance in the advanced histological stages suggests that an estrogenic deficiency could favour the evolution of this disease toward ductopenia.