N-Cadherin Distinguishes Intrahepatic Cholangiocarcinoma from Liver Metastases of Ductal Adenocarcinoma of the Pancreas

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 thera...

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Bibliographic Details
Published in:Cancers 2022-06, Vol.14 (13), p.3091
Main Authors: 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.
Format: Article
Language:English
Subjects:
Adenocarcinoma
Adherens junctions
Bile ducts
Cancer
Carcinoma
Cell differentiation
Chemotherapy
Cholangiocarcinoma
Cloning
Differential diagnosis
E-cadherin
Fluorescence microscopy
Gallbladder
Glycoproteins
Hepatocytes
Image processing
Immunohistochemistry
Liver
Liver cancer
Localization
Medical prognosis
Metastases
Metastasis
Microscopy
Monoclonal antibodies
N-Cadherin
Pancreas
Phenotypes
Proteins
Reagents
Tumors
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Summary: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.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers14133091