Estrogen receptors in cholangiocytes and the progression of primary biliary cirrhosis
Estrogen receptors in cholangiocytes and the progression of primary biliary cirrhosis
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DOI：
10.1016/j.jhep.2004.08.022
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发表时间：
2004-12-01
影响因子：
25.7
通讯作者：
Gaudio, E
中科院分区：
文献类型：
--
作者：
Alvaro, D;Invernizzi, P;Gaudio, E
背景/目标：方法：采用免疫组织化学方法检测原发性胆汁性肝硬化（PBC）患者肝活检组织中雌激素受体（ER）的表达，并结合细胞角蛋白19（CK 19）、增殖细胞核抗原（PCNA）、Fas和末端脱氧核苷酸转移酶末端标记（TUNEL）技术，探讨PBC患者肝组织中ER的表达及其与细胞增殖和死亡的关系。结果：原发性硬化性胆管炎和酒精性肝硬化患者的胆管细胞ER-α和ER-β均呈阳性表达，而正常肝组织中无ER-α和ER-β表达。在PBC中，ER-β的阳性率在所有组织学阶段都很高（50- 65%），而ER-α的阳性率从I期的1%增加到III期的12%（阳性与PCNA相关并共定位于同一细胞中）。在PBC的IV期，胆管细胞ER-α阴性，与较低的PCNA阳性和最大程度的胆管减少相关。PBC患者胆管细胞ER-α阳性率明显低于原发性硬化性胆管炎和酒精性肝硬化。结论：ER在PBC和其他与胆管细胞增殖相关的病变中表达，而在正常人中不表达。ER-α在PBC中的低表达及其在晚期组织学阶段的消失表明雌激素缺乏可能有利于这种疾病向导管减少症的演变。(C)2004年欧洲肝脏研究协会。Elsevier B. V.出版，保留所有权利。
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. (C) 2004 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.