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.
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.
Authors: Sue K Park; Gabriella Andreotti; Asif Rashid; Jinbo Chen; Philip S Rosenberg; Kai Yu; Jennifer Olsen; Yu-Tang Gao; Jie Deng; Lori C Sakoda; Mingdong Zhang; Ming-Chang Shen; Bing-Sheng Wang; Tian-Quan Han; Bai-He Zhang; Meredith Yeager; Stephen J Chanock; Ann W Hsing Journal: Carcinogenesis Date: 2010-02-19 Impact factor: 4.944
Authors: Romina Mancinelli; Paolo Onori; Eugenio Gaudio; Antonio Franchitto; Guido Carpino; Yoshiyuki Ueno; Domenico Alvaro; Luigi P Annarale; Sharon Demorrow; Heather Francis Journal: Exp Biol Med (Maywood) Date: 2009-02-20
Authors: Craig Lammert; Douglas L Nguyen; Brian D Juran; Erik Schlicht; Joseph J Larson; Elizabeth J Atkinson; Konstantinos N Lazaridis Journal: Dig Liver Dis Date: 2013-03-11 Impact factor: 4.088
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