Sasaki M, Nakanuma Y, Kim Y S
Department of Pathology (II), Kanazawa University School of Medicine, Japan.
Hepatology. 1996 Nov;24(5):1074-8. doi: 10.1002/hep.510240516.
To date, seven apomucins have been characterized and their expression in malignant and premalignant lesions is under evaluation. In this study, we examined the expression of MUC1, MUC2, MUC3, and MUC5/6 apomucins in cholangiocarcinoma (CC) and biliary epithelial dysplasia. We used 14 liver samples from patients with hepatolithiasis and CC, 11 with hepatolithiasis showing biliary epithelial dysplasia, 31 with CC alone (19 hilar, 10 peripheral, and 2 unclassifiable), and 14 with combined hepatocellular-cholangiocellular carcinoma (HC-CC) and immunohistochemically characterized the expression profiles of apomucins. Nondysplastic biliary epithelial cells in the intrahepatic large bile ducts constantly expressed MUC3 apomucin. MUC5/6 and MUC3 apomucin expression was widespread in dysplastic biliary epithelial cells in hepatolithiasis, although the latter was reduced or absent in dysplastic foci. CC extensively expressed MUC1 apomucin and focally expressed MUC2 apomucin. In addition, CC of the hilar type, including those with hepatolithiasis, frequently expressed MUC3 apomucin (68% and 57%, respectively), whereas those of the peripheral type infrequently expressed MUC3 apomucin (10%) (P < .01). MUC5/6 apomucin was more frequently expressed in well-differentiated (89%), compared with poorly differentiated CC (42%) (P < .01). Cholangiocellular elements of combined HC-CC frequently expressed MUC1 apomucin, although they rarely expressed MUC2 and MUC3 apomucin and infrequently expressed MUC5/6 apomucin. The frequent and aberrant expression of "gastric type" MUC5/6 apomucin in biliary epithelial dysplasia, as well as in CC, suggests that biliary epithelial cells gain a gastric apomucin phenotype during carcinogenesis. MUC3 apomucin expression in CC is a marker that suggests that CC arises in the intrahepatic large bile ducts.
迄今为止，已有7种脱辅基粘蛋白得到鉴定，它们在恶性和癌前病变中的表达正在评估中。在本研究中，我们检测了粘蛋白1（MUC1）、粘蛋白2（MUC2）、粘蛋白3（MUC3）和粘蛋白5/6（MUC5/6）脱辅基粘蛋白在胆管癌（CC）和胆管上皮发育异常中的表达。我们使用了14例来自肝内胆管结石和CC患者的肝脏样本、11例伴有胆管上皮发育异常的肝内胆管结石患者的样本、31例单纯CC患者的样本（19例肝门部、10例周围型和2例无法分类）以及14例肝细胞-胆管细胞癌（HC-CC）合并患者的样本，并通过免疫组化对脱辅基粘蛋白的表达谱进行了鉴定。肝内大胆管的非发育异常胆管上皮细胞持续表达MUC3脱辅基粘蛋白。MUC5/6和MUC3脱辅基粘蛋白在肝内胆管结石的发育异常胆管上皮细胞中广泛表达，尽管后者在发育异常灶中表达减少或缺失。CC广泛表达MUC1脱辅基粘蛋白，局灶性表达MUC2脱辅基粘蛋白。此外，包括合并肝内胆管结石的患者在内，肝门型CC经常表达MUC3脱辅基粘蛋白（分别为68%和57%），而周围型CC很少表达MUC3脱辅基粘蛋白（10%）（P<0.01）。与低分化CC（42%）相比，MUC5/6脱辅基粘蛋白在高分化CC中更常表达（89%）（P<0.01）。HC-CC合并中的胆管细胞成分经常表达MUC1脱辅基粘蛋白，尽管它们很少表达MUC2和MUC3脱辅基粘蛋白，且很少表达MUC5/6脱辅基粘蛋白。“胃型”MUC5/6脱辅基粘蛋白在胆管上皮发育异常以及CC中频繁且异常表达，提示胆管上皮细胞在癌变过程中获得了胃脱辅基粘蛋白表型。CC中MUC3脱辅基粘蛋白的表达是一个标志物，提示CC起源于肝内大胆管。
