N-cadherin serves as diagnostic biomarker in intrahepatic and perihilar cholangiocarcinomas

Abstract

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 ¼ 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.

Viral hepatitis is associated with intrahepatic cholangiocarcinoma with cholangiolar differentiation and N-cadherin expression

“…N-cadherin is more frequently expressed in peripheral than in hilar cholangiocarcinomas, 21 which suggests that N-cadherin is more likely to be expressed in tumors differentiating toward small bile duct morphology. Therefore, we tested the expression of N-cadherin in resected specimen of intrahepatic cholangiocarcinomas and found N-cadherin expression was highly correlated with viral hepatitis infection (OR ¼ 5.06, P ¼ 0.0002) (Figure 3).…”

Overexpression of ATA1/SLC38A1 Predicts Future Recurrence and Death in Chinese Patients with Hilar Cholangiocarcinoma

“…into the Cox regression model [11,34], which might be useful in predicting disease-free survival and overall survival in patients after resection of hilar cholangiocarcinoma. Energy metabolism is dysregulated in the proliferation of tumor cells, and more amino acids are need.…”

Annexin-1 Downregulation Is Associated with Clinical Outcome in Chinese Patients with Hilar Cholangiocarcinoma

“…Even with tumor-free margins, the patients' outcome remains different. Other genetic biomarkers were introduced into the Cox regression model of hilar cholangiocarcinoma, notably including MMPs, Bmi, MVD, N-cadherin, [32][33][34][35] . ANXA1 is a novel biomarker in predicting patients' clinical outcome.…”