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World J Gastrointest Oncol. Oct 15, 2016; 8(10): 725-734
Published online Oct 15, 2016. doi: 10.4251/wjgo.v8.i10.725
Mucins in neoplasms of pancreas, ampulla of Vater and biliary system
Dimitrios Moschovis, Giorgos Bamias, Ioanna Delladetsima
Dimitrios Moschovis, Department of Gastroenterology, Agios Panteleimon General Hospital, 18453 Nikea, Greece
Giorgos Bamias, Academic Department of Gastroenterology, Medical School, National and Kapodistrian University of Athens, Laikon Hospital, 11527 Athens, Greece
Ioanna Delladetsima, First Department of Pathology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
Author contributions: All authors equally contributed to this paper with conception and design of the study, literature review and analysis, drafting and critical revision and editing, and final approval of the final version.
Conflict-of-interest statement: No potential conflicts of interest. No financial support.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Ioanna Delladetsima, Associate Professor, First Department of Pathology, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Street, Goudi, 11527 Athens, Greece. jokadelladetsima@hotmail.com
Telephone: +30-210-7456485 Fax: +30-213-2061794
Received: May 10, 2016
Peer-review started: May 11, 2016
First decision: July 4, 2016
Revised: July 19, 2016
Accepted: August 15, 2016
Article in press: August 15, 2016
Published online: October 15, 2016
Processing time: 142 Days and 19 Hours
Abstract

Tumors of the pancreas, the ampulla of Vater, and the extrahepatic and intrahepatic bile ducts have significant histological similarities due to the common embryonic origin of the pancreatobiliary system. This obviates the need for discovery of biomarkers with diagnostic and prognostic value for these tumors. Mucins, especially MUC-1, -2, -4 and -5AC, are important candidates for developing into such reliable biomarkers. Increased expression of MUC1 occurs in pancreatic ductal adenocarcinomas and is associated with increased degrees of dysplasia in pancreatic intraepithelial neoplasia (PanIN). Positive expression of MUC2 in intraductal papillary mucinus neoplasms (IPMN) of the intestinal type indicates high potential progression to invasive carcinoma with de novo expression of MUC1, while absence of MUC2 expression in IPMNs of gastric type implies low potential to malignant evolution. De novo MUC4 expression correlates to the severity of dysplasia in PanIN and is associated with a poor prognosis in patients with pancreatic ductal adenocarcinomas. In biliary intraepithelial neoplasia (BilIN), increased expression of MUC1 is associated with higher degrees of dysplasia. Intrahepatic cholangiocarcinomas (ICC) are characterized by increased expression of all glycoforms of MUC1. Positive MUC2 expression in intraductal papillary neoplasm of the bile ducts (IPNB) of the intestinal type indicates high malignant potential with de novo expression of MUC1 in the invasive element. Absent MUC2 expression in any degree of BilIN may prove useful in differentiating them from IPNB. De novo expression of MUC4 is associated with poor prognosis in patients with ICC or carcinoma of the extrahepatic bile ducts (EHBDC). High de novo expression of MUC5AC is found in all degrees of BilIN and all types of IPNB and ICC. The MUC5AC is useful in the detection of neoplastic lesions of the bile duct at an early stage. Increased expression of mucin MUC1 in carcinoma of the ampulla of Vater associated with unfavorable behavior of the tumor, such as lymph node metastasis, infiltration of the pancreas and duodenum, advanced TNM classification and worse prognosis. Patients with intra-ampullary papillary-tubular neoplasm (IAPN) of the pancreatobiliary immunophenotype did not show MUC2, while those of the intestinal immunophenotype are MUC2 positive. The expression of MUC4 is associated with poor prognosis in patients with carcinoma of the ampulla of Vater favoring metastasis and making them resistant to apoptosis. Moreover, it appears that MUC4 positivity correlates with recurrence of the tumor. Expression of MUC5AC is associated with the invasive potential of the tumor.

Keywords: Ampulla Vater neoplasms; Biliary system neoplasms; Mucins; Pancreatic neoplasms

Core tip: The combined status of mucin expression may be useful in the differential diagnosis of pancreatobiliary neoplasms, the detection of pre-malignant lesions and the evaluation of their malignant behavior. Besides their diagnostic and prognostic role, their involvement in carcinogenesis reveals their importance as putative therapeutic targets in the future.