Claudin-1, −2, −3, −4, −7, −8, and −10 Protein Expression in Biliary Tract Cancers

Abstract

Biliary tract cancers are relatively common malignant gastrointestinal tumors in the elderly. Claudins are integral components of tight junctions that play important roles in maintaining epithelial cell polarity, controlling paracellular diffusion, and regulating cell growth and differentiation. The expression profile of claudins has been extensively characterized, but few reports exist on their expression in the normal and neoplastic biliary tract. Our aim was therefore to study claudins by IHC reactions in normal and neoplastic biliary tract samples. We detected that claudin expressions differ in the normal sample groups: the normal gallbladder strongly expressed claudin-2, −3, −4, and −10, but only weak reactions were seen in normal intrahepatic bile ducts. Although each cancer type expressed several claudins with various intensities, only claudin-4 presented especially strong immunoreactions in extrahepatic bile duct cancers and gallbladder carcinomas, whereas claudin-1 and −10 presented in intrahepatic bile duct cancers. Comparing the normal and carcinoma groups, the most significant decrease was detected in the expression of claudin-10. In conclusion, the expression pattern of claudins is different in the various parts of the normal and neoplastic biliary tract; moreover, an unequivocal decrease was detected in the carcinomas compared with their corresponding normal samples. This manuscript contains online supplemental material at http://www.jhc.org . Please visit this article online to view these materials.

Distinct Claudin Expression Profiles of Hepatocellular Carcinoma and Metastatic Colorectal and Pancreatic Carcinomas

“…Claudin-7 positivity was described in all primary pancreatic adenocarcinomas (Borka et al 2007) whereas, in PLMs, 6 cases were negative, and only 9 of 15 cases were faintly positive. In this regard, PLM appears to be more similar to bile duct cancers, which also exhibit low claudin-7 expression (Nemeth et al 2009). …”

Expression of Tight Junction Components in Hepatocyte-Like Cells Differentiated from Human Embryonic Stem Cells

“…Parenchymal cells of the liver, i.e., hepatocytes and bile duct cells (cholangiocytes) play distinct roles in diverse hepatic functions, thus, they differ from each other in several aspects including expression pattern of cytokeratins, ABC transporter proteins, and tight junction (TJ) components [7][8][9].…”

“…Claudin-5 component is typically expressed in the endothelial cells [22], however it can be expressed in certain tumors such as in fibrolamellar carcinoma of the liver [27]. In normal liver the hepatocytes were found to be negative for claudin-7 and the normal biliary epithelial cells showed intense basolateral membrane claudin-7 positivity [8,24,30].…”

Sex-Dependent Claudin-1 Expression in the Liver of Euthyroid and Hypothyroid Mice

“…For instance, in the neonatal ichthyosis-sclerosing cholangitis syndrome, claudin-1 gene mutations may lead to increased paracellular permeability between bile duct epithelial cells [11] . Other examples are familial hypercholanemia with claudin-1 mutations [12] , acute acalculous cholecystitis with decreased claudin-1 [13] , and intrahepatic cholangiocarcinoma with elevated claudin-1 expression [14] .…”