Gerber Tiemo S, Goeppert Benjamin, Hausen Anne, Witzel Hagen R, Bartsch Fabian, Schindeldecker Mario, Gröger Lisa-Katharina, Ridder Dirk A, Cahyadi Oscar, Esposito Irene, Gaida Matthias M, Schirmacher Peter, Galle Peter R, Lang Hauke, Roth Wilfried, Straub Beate K
Institute of Pathology, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany.
Institute of Pathology and Neuropathology, RKH Klinikum Ludwigsburg, 71640 Ludwigsburg, Germany.
Cancers (Basel). 2022 Jun 23;14(13):3091. doi: 10.3390/cancers14133091.
Carcinomas of the pancreatobiliary system confer an especially unfavorable prognosis. The differential diagnosis of intrahepatic cholangiocarcinoma (iCCA) and its subtypes versus liver metastasis of ductal adenocarcinoma of the pancreas (PDAC) is clinically important to allow the best possible therapy. We could previously show that E-cadherin and N-cadherin, transmembrane glycoproteins of adherens junctions, are characteristic features of hepatocytes and cholangiocytes. We therefore analyzed E-cadherin and N-cadherin in the embryonally related epithelia of the bile duct and pancreas, as well as in 312 iCCAs, 513 carcinomas of the extrahepatic bile ducts, 228 gallbladder carcinomas, 131 PDACs, and precursor lesions, with immunohistochemistry combined with image analysis, fluorescence microscopy, and immunoblots. In the physiological liver, N-cadherin colocalizes with E-cadherin in small intrahepatic bile ducts, whereas larger bile ducts and pancreatic ducts are positive for E-cadherin but contain decreasing amounts of N-cadherin. N-cadherin was highly expressed in most iCCAs, whereas in PDACs, N-cadherin was negative or only faintly expressed. E- and N-cadherin expression in tumors of the pancreaticobiliary tract recapitulate their expression in their normal tissue counterparts. N-cadherin is a helpful marker for the differential diagnosis between iCCA and PDAC, with a specificity of 96% and a sensitivity of 67% for small duct iCCAs and 50% for large duct iCCAs.
胰胆系统癌的预后尤其不佳。肝内胆管癌（iCCA）及其亚型与胰腺导管腺癌（PDAC）肝转移的鉴别诊断在临床上具有重要意义，以便能采取最佳治疗方案。我们之前能够证明，E-钙黏蛋白和N-钙黏蛋白作为黏着连接的跨膜糖蛋白，是肝细胞和胆管细胞的特征性标志物。因此，我们采用免疫组织化学结合图像分析、荧光显微镜检查和免疫印迹法，分析了胆管和胰腺胚胎相关上皮以及312例iCCA、513例肝外胆管癌、228例胆囊癌、131例PDAC及其前体病变中的E-钙黏蛋白和N-钙黏蛋白。在正常肝脏中，N-钙黏蛋白在肝内小胆管中与E-钙黏蛋白共定位，而较大的胆管和胰管E-钙黏蛋白呈阳性，但N-钙黏蛋白含量逐渐减少。N-钙黏蛋白在大多数iCCA中高表达，而在PDAC中，N-钙黏蛋白呈阴性或仅微弱表达。胰胆管肿瘤中E-钙黏蛋白和N-钙黏蛋白的表达与其正常组织对应物中的表达情况相符。N-钙黏蛋白是鉴别iCCA和PDAC的有用标志物，对小胆管iCCA的特异性为96%，敏感性为67%，对大胆管iCCA的敏感性为50%。
