N-cadherin serves as diagnostic biomarker in intrahepatic and perihilar cholangiocarcinomas
N-cadherin serves as diagnostic biomarker in intrahepatic and perihilar cholangiocarcinomas
复制标题
DOI：
10.1038/modpathol.2008.123
复制
发表时间：
2009-02-01
期刊：
影响因子：
7.5
通讯作者：
Laboisse, Christian L.
中科院分区：
文献类型：
--
作者：
Mosnier, Jean-Francois;Kandel, Christine;Laboisse, Christian L.
由于该肿瘤缺乏明确的免疫特征，肝内胆管癌的组织病理学诊断很困难。本研究的目的是探讨肝内胆管肿瘤中 E- 和 N-钙粘蛋白的表达，并确定它们在鉴别诊断中的潜在意义。研究对象为白种人正常肝组织、5例肝硬化伴胆管反应、5例局灶性结节性增生、5例胆管错构瘤、5例胆管腺瘤和45例肝内胆管癌。构建了组织微阵列，包括20个食管癌、86个胃癌、8个小肠癌、64个结肠癌、18个胰腺癌、6个胆囊癌和7个肝外胆道腺癌、22个肝细胞癌和正常组织。使用E-钙粘蛋白、N-钙粘蛋白、NCAM、Hep Par1和细胞角蛋白7、19和20进行免疫组织化学。对冷冻肝组织进行免疫印迹分析以控制所用E-和N-钙粘蛋白抗体的特异性。在正常肝脏中，肝内胆管的上皮细胞（无论其口径如何）以及肝细胞在其质膜上共表达E-钙粘蛋白和N-钙粘蛋白。在肝硬化中，导管反应完全表达E-和N-钙粘蛋白。所有良性病变和 45 例肝内胆管癌中的 30 例（23/29 外周癌和 7/16 肝门癌）也表达 N-钙粘蛋白。在所有病变中均检测到E-钙粘蛋白。 N-钙粘蛋白在肿瘤细胞质膜上的表达在外周细胞中明显高于肝门部肝内胆管癌（P = 0.003）。在非胆管癌中，只有1%的胃腺癌和66%的胆囊腺癌以及所有的肝细胞癌在肿瘤细胞膜上表达N-钙粘蛋白。最后，对于肝内胆管癌的诊断，N-钙粘蛋白膜表达的特异性值为88%，而细胞角蛋白7/膜N-钙粘蛋白组合的特异性值为98%。在胃肠道和肝脏中，膜状N-钙粘蛋白仅限于肝细胞和肝内胆管细胞。与细胞角蛋白 7 和 Hep Par1 结合，N-钙粘蛋白是原发性肝肿瘤组织病理学诊断的可靠工具。
As a definite immunoprofile of this tumor is missing, the histopathologic diagnosis of intrahepatic cholangiocarcinoma is difficult. The aim of this study was to explore E- and N-cadherin expressions in intrahepatic bile duct tumors, and to determine their potential interest in differential diagnosis. Normal liver tissue, 5 cirrhosis with ductular reaction, 5 focal nodular hyperplasia, 5 bile duct hamartomas, 5 bile duct adenomas, and 45 intrahepatic cholangiocarcinomas from Causasian patients were studied. Tissue-microarrays including 20 esophageal, 86 gastric, 8 small bowel, 64 colonic, 18 pancreatic, 6 gallbladder, and 7 extrahepatic biliary tract adenocarcinomas, 22 hepatocellular carcinomas, and normal tissues were constructed. Immunohistochemistry was performed using E- cadherin, N-cadherin, NCAM, Hep Par1, and cytokeratins 7, 19 and 20. Immunoblot analysis of frozen liver tissues was performed to control the specificity of E- and N-cadherin antibodies used. In normal liver, epithelial cells of intrahepatic bile ducts, whatever their caliber, as well as hepatocytes, coexpressed E- and N-cadherins at their plasma membranes. In cirrhosis, ductular reactions completely expressed E- and N-cadherins. All the benign lesions and 30 of the 45 intrahepatic cholangiocarcinomas (23/29 peripheral and 7/16 hilar) also expressed N-cadherin. E-cadherin was detected in all the lesions. The expression of N-cadherin at the plasma membrane of tumor cells was significantly more frequent in peripheral than in hilar intrahepatic cholangiocarcinomas (P = 0.003). Among noncholangiocarcinomas, only 1% gastric and 66% gallbladder adenocarcinomas and all the hepatocellular carcinomas expressed N-cadherin at the membrane of tumor cells. Finally, for the diagnosis of intrahepatic cholangiocarcinomas, the specificity value of membranous expression of N-cadherin was 88%, whereas that of the combination cytokeratin 7/membranous N-cadherin was 98%. In the gastrointestinal and liver tract, membranous N-cadherin is restricted to the hepatocytes and intrahepatic biliary cells. In combination with cytokeratin 7 and Hep Par1, N-cadherin is a reliable tool for the histopathological diagnosis of primary hepatic tumors.