Different expression patterns of mucin core proteins and cytokeratins during intrahepatic cholangiocarcinogenesis from biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile duct - an immunohistochemical study of 110 cases of hepatolithiasis
Different expression patterns of mucin core proteins and cytokeratins during intrahepatic cholangiocarcinogenesis from biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile duct - an immunohistochemical study of 110 cases of hepatolithiasis
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DOI：
10.1016/j.jhep.2005.09.025
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发表时间：
2006-02-01
影响因子：
25.7
通讯作者：
Nakanuma, Y
中科院分区：
文献类型：
--
作者：
Zen, Y;Sasaki, M;Nakanuma, Y
背景/目标：浸润性肝内胆管细胞癌（ICC）之前的两种类型的肿瘤病变被确定：一个扁平型肿瘤病变称为“胆管上皮内瘤变（BilIN）”和胆管内乳头状肿瘤（IPN-B）。在这两种病变中，多步骤的致癌作用已被提出，尽管在此过程中的表型变化仍不清楚。方法：我们用免疫化学方法检测了110例肝内胆管结石中BilIN、IPN-B和ICC中MUC 1、MUC 2、MUC 5AC、细胞角蛋白7（CK 7）和CK 20的表达模式。37例肝胆管结石内胆管癌分为18例胆管腺癌伴BilIN，10例胆管腺癌伴IPN-B，9例胶质癌伴IPN-B。通过BilIN的致癌作用的特征在于MUC 2-/CK 7 +/CK 20-，MUC 1增加。表情IPN-B以肠表型（MUC 2 +/CK 20+）为特征，导致管状腺癌的癌变与MUC 1表达增加相关，导致胶质癌的癌变与MUC 1阴性相关。胆管癌伴BILIN或IPN-B的病理分期较伴IPN-B的胶样癌提前。结论：MUCs和细胞角蛋白的免疫表型可能是肝胆管结石发生胆管癌的3条途径的特征。MUC 1在BilIN和IPN-B中的表达增加与管状腺癌相关，而IPN-B中的胶样癌的特征在于MUC 1阴性和较低的病理分期。(C)2005年欧洲肝脏研究协会。Elsevier B. V.出版，保留所有权利。
Background/Aims: Two types of neoplastic lesions preceding invasive intrahepatic cholangiocarcinoma (ICC) are identified: a flat-type neoplastic lesion called 'biliary intraepithelial neoplasia (BilIN)' and an intraductal papillary neoplasm of the bile duct (IPN-B). Multi-step carcinogenesis has been suggested in both lesions, although phenotypic changes during this process remain unclarified.Methods: We immunohistochemically examined expression patterns of MUC1, MUC2, MUC5AC, cytokeratin 7 (CK7), and CK20 in BilIN, IPN-B, and ICC in 110 cases of hepatolithiasis.Results: Thirty-seven cases of ICC in hepatolithiasis were divided into 18 tubular adenocarcinomas with BilIN, 10 tubular adenocarcinomas with IPN-B and nine colloid carcinomas with IPN-B. Carcinogenesis via BilIN was characterized by MUC2-/CK7+/CK20 - with increasing MUC1. expression. IPN-B was characterized by the intestinal phenotype (MUC2+/CK20+), and carcinogenesis leading to tubular adenocarcinoma was associated with increasing MUC1 expression and that to colloid carcinoma with MUC1-negativity. Pathological stages of tubular adenocarcinoma of ICC with BilIN or IPN-B were more advanced than those of colloid carcinoma with IPN-B.Conclusions: Immunophenotypes of MUCs and cytokeratins might characterize three cholangiocarcinogenetic pathways in hepatolithiasis. Increased expression of MUC1 in BilIN and also IPN-B is associated with tubular adenocarcinoma, while colloid carcinoma in IPN-B is characterized by MUC1-negativity and less advanced pathologic stages. (C) 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.