Significance of mucin expression in pancreatobiliary neoplasms

Abstract

Mucins are high molecular weight glycoproteins that play important roles in carcinogenesis and tumor invasion. We have described, for the first time, that pancreatic ductal adenocarcinomas (PDACs) with an aggressive behavior and a poor outcome expressed MUC1 (pan-epithelial membrane-associated mucin) but did not express MUC2 (intestinal-type secreted mucin), whereas intraductal papillary mucinous neoplasms (IPMNs) with indolent behavior and a favorable outcome did not express MUC1 but did express MUC2. These expression profiles of MUC1 and MUC2 related to the prognoses of the patients were also observed in biliary neoplasms such as intrahepatic cholangiocarcinoma (ICC)-mass-forming type (MF), mucin-producing bile duct tumor (MPBT), and extrahepatic bile duct carcinoma (EHBDC). We also found recently that high expression of MUC4 (tracheobronchial membraneassociated mucin) in PDACs, ICCs-MF, and EHBDCs was a new independent poor prognostic factor, although MUC4 was not expressed in normal pancreatobiliary tissue. High de novo expression of MUC5AC (gastric-type secreted mucin) was observed in many types of pancreatobiliary neoplasms, including all grades of pancreatic intraepithelial neoplasia (PanIN) and biliary intraepithelial neoplasia (BilIN), and all types of IPMNs and MPBTs, as well as PDACs and ICCs-MF, although MUC5AC was not expressed in normal pancreatobiliary tissue. The combined status of MUC1, MUC2, MUC4, and MUC5AC expression may be useful for the early detection of pancreatobiliary neoplasms and evaluation of their malignancy. In regard to the mechanism of mucin expression, we have recently reported that MUC1, MUC2, MUC4, and MUC5AC gene expression is regulated by epigenetics (DNA methylation and histone H3 lysine 9 modification) in cancer cell lines, including PDAC cells. Translational research of mucin gene expression mechanisms, including epigenetics, in pancreatobiliary neoplasms may give us new tools for the early and accurate detection of these neoplasms.

GNAS Codon 201 mutations are uncommon in Intraductal Papillary Neoplasms of the Bile Duct

“…20 Although molecular analyses of either of the two biliary precursor lesions are limited, the available information suggests underlying differences in terms of genetic alterations, as well as clinical distinctions in the invasive carcinomas arising in the respective contexts. [21][22][23] Emerging evidence suggests a number of similarities between IPMNs and IPNBs. For example, Zen et al analysed both entities with respect to clinicopathologic features, expression of lineageassociated proteins and prognostic parameters.…”

Diagnostic usefulness of KL-6 concentration of bile in biliary tract cancer

“…Mucins are also expressed in pancreatico-biliary neoplasm included biliary tract cancer. Furthermore, MUC expression pattern might reflect the cell differentiation type of biliary tract cancer like pancreatic intraductal papillary mucinus neoplasms, for example, gastric type presents a MUC1-/MUC2-/MUC5AC+/MUC6-profile, intestinal type presents a MUC1-/MUC2+/MUC5AC+/MUC6-profile, and pancreaticobiliary type presents a MUC1+/MUC2-/MUC5AC+/MUC6+ profile (5,6).…”

Mucins and NCAM (CD56) in intrahepatic cholangiocarcinogenesis

“…MUC6 was positive in 31.3% of dysplasias, and 18.2% in CC. Several authors demonstrated higher expression of these mucins in both CC and dysplastic epithelium, emphasizing that they are important in characterizing biliary and pancreatic pre-neoplastic lesions (7,11,15,20,21,24) . Although these results apparently substantiate the usefulness of mucins 5 and 6 in the characterization of preneoplastic lesions, we observed that both were also expressed in reactive epithelium in 40.3% and 11.9%, respectively.…”

“…Although these results apparently substantiate the usefulness of mucins 5 and 6 in the characterization of preneoplastic lesions, we observed that both were also expressed in reactive epithelium in 40.3% and 11.9%, respectively. Up to now, studies describing the expression of gastric mucins in reactive biliary epithelium were not found in the literature (15,23,21) . Thus, gastric mucin expression in the reactional epithelium of intrahepatic bile ducts, associated with the lack of statistical significance of dysplasia expression, points to a limited role of these mucins in distinguishing reactive and pre-neoplastic lesions.…”