Role of MUC Genes and Mucins in Pancreatic Neoplasia

The paper by Andrianifahanana et al. (1), published in this issue of the Americal Journal of Gastroenterology, is one of the latest important additions to the literature evolving on the role of mucins (and MUCs) in carcinogenesis to which these authors have already made several contributions (2–5). Mucins, the main constituents of mucous, are large glycoproteins that are in fact present in a variety of cell types. While their main function is the protection of epithelium from potential injurious agents, they are being increasingly recognized for having complex associations with various cellular pathways, ultimately impacting cell growth, cell–cell and cell– stroma interactions, as well as cellular response to immunity. Human mucin genes, designated as MUCs, share the common characteristics of large size of their mRNAs and large nucleotide tandem repeat domains. To date, 21 distinct types have been characterized, most of which belong to one of two categories (6): 1) secretory or gel-forming (MUC2, MUC5A, MUC5B, MUC6), and 2) membrane-bound (MUC1, MUC3, MUC4, MUC12, MUC17). The expression profile and physiologic role of different MUC types vary significantly from tissue to tissue, from one tumor type to another, and even from neoplasms of similar type that occur in different sites (7). As information on the molecular biologic aspects of these molecules evolves, it is crucial to incorporate the perspectives of different disciplines so that the significance of these findings can be elucidated. Mucins have long been recognized by pathologists who have incorporated them into the classification and terminology of neoplasia (8, 9). The pancreas is one of the best examples (if not the prototypical) of how the presence or absence and the amount of mucin, as well as the type and pattern of mucin expression have been instrumental not only in pathologic classification, but also in diagnosis and prognostication of neoplasia. When histomorphologic observations were combined with immunohistochemical analysis of human tumors, the ultimate method to verify the specific expression profiles of molecules in the tumor cells themselves, the following important applications of mucins have been established:

[1]  S. Batra,et al.  Characterization of Human Mucin MUC17 , 2006, Journal of Biological Chemistry.

[2]  S. Chari,et al.  International Consensus Guidelines for Management of Intraductal Papillary Mucinous Neoplasms and Mucinous Cystic Neoplasms of the Pancreas , 2006, Pancreatology.

[3]  O. Basturk,et al.  Invasive micropapillary carcinomas of the ampullo-pancreatobiliary region and their association with tumor-infiltrating neutrophils , 2005, Modern Pathology.

[4]  D. Klimstra,et al.  Not all “mucinous carcinomas” are equal: time to redefine and reinvestigate the biologic significance of mucin types and patterns in the GI tract , 2005, Virchows Archiv.

[5]  T. Smyrk.  Surgical Pathology of the GI Tract, Liver, Biliary Tract and Pancreas , 2004 .

[6]  D. Grignon,et al.  Pathogenesis of invasive micropapillary carcinoma: role of MUC1 glycoprotein , 2004, Modern Pathology.

[7]  S. Batra,et al.  A role for human MUC4 mucin gene, the ErbB2 ligand, as a target of TGF-β in pancreatic carcinogenesis , 2004, Oncogene.

[8]  Olca Basturk,et al.  Pathologically and Biologically Distinct Types of Epithelium in Intraductal Papillary Mucinous Neoplasms: Delineation of an “Intestinal” Pathway of Carcinogenesis in the Pancreas , 2004, The American journal of surgical pathology.

[9]  N. Porchet,et al.  Les gènes MUC : Mucin or not mucin ? That is the question , 2004 .

[10]  Kohzoh Imai,et al.  MUC4 is a novel prognostic factor of intrahepatic cholangiocarcinoma‐mass forming type , 2004, Hepatology.

[11]  D. Klimstra.  Benign and Malignant Tumors of the Pancreas , 2004 .

[12]  N. Porchet,et al.  [MUC genes: mucin or not mucin? That is the question]. , 2004, Medecine sciences : M/S.

[13]  J. Goldblum,et al.  Surgical Pathology of the GI Tract, Liver, Biliary Tract, and Pancreas , 2003 .

[14]  F. Sarkar,et al.  Clinicopathological Correlates of Pancreatic Intraepithelial Neoplasia: A Comparative Analysis of 82 Cases With and 152 Cases Without Pancreatic Ductal Adenocarcinoma , 2003, Modern Pathology.

[15]  K. Imai,et al.  New classification of pancreatic intraductal papillary–mucinous tumour by mucin expression: its relationship with potential for malignancy , 2002, The Journal of pathology.

[16]  J. Cameron,et al.  MUC4 expression increases progressively in pancreatic intraepithelial neoplasia. , 2002, American journal of clinical pathology.

[17]  H. Friess,et al.  Mucin (MUC) gene expression in human pancreatic adenocarcinoma and chronic pancreatitis: a potential role of MUC4 as a tumor marker of diagnostic significance. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[18]  G. Zamboni,et al.  The Immunohistochemical Mucin Expression Pattern Distinguishes Different Types of Intraductal Papillary Mucinous Neoplasms of the Pancreas and Determines Their Relationship to Mucinous Noncystic Carcinoma and Ductal Adenocarcinoma , 2001, The American journal of surgical pathology.

[19]  R H Hruban,et al.  Pancreatic Intraepithelial Neoplasia: A New Nomenclature and Classification System for Pancreatic Duct Lesions , 2001, The American journal of surgical pathology.

[20]  F. Sarkar,et al.  Colloid (Mucinous Noncystic) Carcinoma of the Pancreas , 2001, The American journal of surgical pathology.

[21]  G. Klöppel,et al.  WHO-classification 2000: exocrine pancreatic tumors. , 2001, Verhandlungen der Deutschen Gesellschaft fur Pathologie.

[22]  S. Takao,et al.  MUC‐1 mucin expression in invasive areas of intraductal papillary mucinous tumors of the pancreas , 1998, Pathology international.

[23]  S. Batra,et al.  Expression of the human mucin gene, Muc 1, in normal tissues and metastatic pancreatic tumors , 1991, International journal of pancreatology : official journal of the International Association of Pancreatology.