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Expression of MUC5AC and MUC6 in invasive ductal carcinoma of the pancreas and relationship with prognosis

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Abstract

Aim/Background. MUC5AC and MUC6 are two major types of mucin that are abundantly present in the stomach; both of them form a gel of high viscosity that provides protection and lubrication. Expressions of MUC5AC and MUC6 are seen in pancreatic neoplasms, whereas the relationships between MUC5AC/MUC6 expression and clinicopathological factors and patient prognosis in invasive ductal carcinoma (IDC) of the pancreas have not been investigated. The aim of this study was to investigate MUC5AC and MUC6 expressions in IDC with special reference to clinicopathological factors and patient prognosis.

Methods. Tissue samples were taken from 33 patients with IDC of the pancreas after radical surgical treatment. MUC5AC and MUC6 expressions were examined immunohistochemically.

Results. The expressions of MUC5AC and MUC6 were observed in the cytoplasm of the tumor cells. MUC5AC and MUC6 immunoreactivities in the cancer tissues were found in 21 (63.6%) and 15 (45.5%) of 33 cases of IDC of the pancreas, respectively. MUC5AC-negative expression was associated significantly with lymphatic invasion, venous invasion, lymph node metastasis, and MUC5AC-positive patients showed significant better survival than those MUC5AC-negative patients. MUC6 expression was significantly related to tumor location, whereas MUC6 expression did not show significant relationship with patient survival.

Conclusion. The results indicate that MUC5AC expression plays an important role in impacting tumor progression in IDC of the pancreas. MUC5AC expression is a benefit to better survival of patients with IDC of the pancreas. MUC6 expression is not involved in tumor progression in IDC of the pancreas.

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References

  1. Roussel P, Lamblin G, Lhermitte M, et al. The complexity of mucins. Biochimie 1988;70:1471–1482.

    Article  PubMed  CAS  Google Scholar 

  2. Kim YS, Gum JR Jr, Brockhausen I. Mucin glycoproteins in neoplasia. Glycoconj J 1996;13:693–707.

    Article  PubMed  CAS  Google Scholar 

  3. Kim YS, Gum JR Jr, Crawley SC, et al. Mucin gene and antigen expression in bilipancreatic carcinogenesis. Ann Oncol 1999;10:S51-S55.

    Article  Google Scholar 

  4. Slomiany BL, Slomiany A. Role of mucus in gastric mucosal protection. J Physiol Pharmacol 1991;42:147–161.

    PubMed  CAS  Google Scholar 

  5. LaMont JT. Mucus: the front line of intestinal mucosal defense. Ann NY Acad Sci 1993;664:190–201.

    Article  Google Scholar 

  6. Gendler SJ, Spicer AP. Epithelial mucin gene. Ann Rev Physiol 1995;57:607–634.

    Article  CAS  Google Scholar 

  7. Lapensee L, Paquette Y, Bleau G. Allelic polymprphism and chromosomal localization of the human oviductin gene (MUC9). Fertil Steril 1997;68:702–708.

    Article  PubMed  CAS  Google Scholar 

  8. Shankar V, Pichan P, Eddy RL Jr, et al. Chromosomal localization of a human mucin gene (MUC8) and cloning of the cDNA corresponding to the carboxy terminus. Am J Respir Cell Mol Biol 1997;16:232–241.

    PubMed  CAS  Google Scholar 

  9. Williams SJ, McGuckin MA, Gotley DC, et al. Two novel mucin genes down-regulated in colorectal cancer identified by differential display. Cancer Res 1999;59:4083–4089.

    PubMed  CAS  Google Scholar 

  10. Buisine MP, Devisme L, Degand P, et al. Developmental mucin gene expression in the gastroduodenal tract and accessory digestive glands. II. Duodenum and liver, gallbladder, and pancreas. J Histochem Cytochem 2000;48:1667–1676.

    PubMed  CAS  Google Scholar 

  11. Buisine MP, Devisme L, Maunoury V, et al. Developmental mucin gene expression in the gastroduodenal tract and accessory digestive glands. I. Stomach. A relationship to gastric carcinoma. J Histochem Cytochem 2000;48:1657–1666.

    PubMed  CAS  Google Scholar 

  12. Ho SB, Kim YS. Carbohydrate antigens on cancerassociated mucin-like molecules. Semin Cancer Biol 1991;2:389–400.

    PubMed  CAS  Google Scholar 

  13. Kimura W, Nagai H, Kuroda A, et al. Analysis of small cystic lesions of the pancreas. Int J Pancreatol 1995;18:197–206.

    PubMed  CAS  Google Scholar 

  14. Kimura W, Morikane K, Esaki Y, et al. Histological and biological patterns of microscopic pancreatic ductal adenocarcinoma detected incidentally at autopsy. Cancer 1998;82:1839–1849.

    Article  PubMed  CAS  Google Scholar 

  15. Kimura W, Sata N, Nakayama H, et al. Pancreatic carcinoma accompanied by pseudocyst: Report of two cases. J Gastroenterol 1994;29:786–791.

    Article  PubMed  CAS  Google Scholar 

  16. Kimura W, Sasahira N, Yoshikawa T, et al. Duct-ectatic type of mucin producing tumor of the pancreas—New concept of pancreatic neoplasia. Hepatogastroenterology 1996;43:692–709.

    PubMed  CAS  Google Scholar 

  17. Yonezawa, S. Application of immunohistochemistry for diagnosis of neoplasms: mucin antigens expression ans biological behavior. Acta Histochem Cytochem 1994;27:561–566.

    Google Scholar 

  18. Osako M, Yonezawa S, Yamashita K, et al. Immunohistochemical studies of mucin antigens in pancreas and intrahepatic bile-duct tumors. J Hepatobiliary Pancreat Surg 1997;4:149–156.

    Article  Google Scholar 

  19. Yonezawa S, Sueyoshi K, Nomoto M, et al. MUC2 gene expression is found in noninvasive tumors but not in invasive tumors of the pancreas and liver: its close relationship with prognosis of the patients. Hum Pathol 1997;28:344–352.

    Article  PubMed  CAS  Google Scholar 

  20. Yonezawa S, Nakamura A, Horinouchi M, et al. The expression of several types of mucins is related to the biological behavior of pancreatic neoplasms. J Hepatobiliary Pancreat Surg 2002;9:328–341.

    Article  PubMed  Google Scholar 

  21. Luttges J, Feyerabend B, Buchelt T, et al. The mucin profile of noninvasive and invasive mucinous cystic neoplasms of the pancreas. Am J Surg Pathol 2002;26:466–471.

    Article  PubMed  CAS  Google Scholar 

  22. Terris B, Dubois S, Buisine MP, et al. Mucin gene expression in intraductal papillary-mucinous pancreatic tumours and related lesions. J Pathol 2002;197:632–637.

    Article  PubMed  CAS  Google Scholar 

  23. Kim GE, Bae HI, Park HU, et al. Abrrant expression of MUC5AC and MUC6 gastric mucins and sialyl Tn antigen in intraepithelial neoplasms of the pancreas. Gastroenterology 2002;123:1052–1060.

    Article  PubMed  CAS  Google Scholar 

  24. Pinto-de-Sousa J, David L, Reis CA, et al. Mucins MUC1, MUC2, MUC5AC and MUC6 expression in the evaluation of differentiation and clinico-biological behaviour of gastric carcinoma. Vichows Arch 2002;440:304–310.

    Article  CAS  Google Scholar 

  25. Ho SB, Shekels LL, Toribara NW, et al. Mucin gene expression in normal, preneoplastic, and neoplastic human gastric epithelium. Cancer Res 1995;55:2681–2690.

    PubMed  CAS  Google Scholar 

  26. De Bolos C, Garrido M, Real FX. MUC6 apomucin shows a distinct normal tissue distribution that correlates with Lewis antigen expression in the human stomach. Gastroenterology 1995;109:723–734.

    Article  PubMed  Google Scholar 

  27. Gum JR Jr, Hicks JW, Toribara NW, et al. Molecular cloning of human intestinal mucin (MUC2) cDNA. Identification of the amino terminus and overall sequence similarity to prepro-von Willebrand factor. J Biol Chem 1994;269:2440–2446.

    PubMed  CAS  Google Scholar 

  28. Toribara NW, Gum JR Jr, Culhane PJ, et al. MUC-2 human small intestinal mucin gene structure. Repeated arrays and polym. J Clin Invest 1991;88:1005–1013.

    Article  PubMed  CAS  Google Scholar 

  29. Meezaman D, Charles P, Daskal E, et al. Cloning and analysis of cDNA encoding a major airway glycoprotein, human tracheobronchial mucin (MUC5). J Biol Chem 1994;269:12,932–12,939.

    CAS  Google Scholar 

  30. Kim YS, Gum JR Jr. Diversity of mucin genes, structure, function, and expression. Gastroenterology 1995;109:999–1001.

    Article  PubMed  CAS  Google Scholar 

  31. Desseyn JL, Aubert JP, Van Seuningen I, et al. Genomic organization of the 3′ region of the human mucin gene MUC5B. J Biol Chem 1997;272:16,873–16,883.

    Article  CAS  Google Scholar 

  32. Toribara NW, Ho SB, Gum, E, et al. The carboxylterminal sequence of the human secretory mucin, MUC6. Analysis of the primary amino acid sequence. J Biol Chem 1997;272:16,398–16,403.

    Article  CAS  Google Scholar 

  33. Yamashita K, Yonezawa S, Tanaka S, et al. Immunohistochemical study of mucin carbohydrates and core proteins in hepatolithiasis and cholangiocarcinoma. Int J Cancer 1993;55:82–91.

    Article  PubMed  CAS  Google Scholar 

  34. Kitamura H, Yonezawa S, Tanaka S, et al. Expression of mucin carbohydrates and core proteins in carcinomas of the ampulla of Vater: their relationship to prognosis. Jpn J Cancer Res 1996;87:631–640.

    PubMed  CAS  Google Scholar 

  35. Yonezawa S, Sato E. Expression of mucin antigens in human cancers and its relationship with malignancy potential. Pathol Int 1997;47:813–830.

    Article  PubMed  CAS  Google Scholar 

  36. Reid CJ, Harris A. Developmental expression of mucin genes in the human gastrointestinal system. Gut 1998;42:220–226.

    Article  PubMed  CAS  Google Scholar 

  37. Balague C, Gambus G, Carrato C, et al. Alatered expression of MUC2, MUC4, and MUC5 mucin genes in pancreas tissues and cancer cell lines. Gastroenterology 1994;106:1054–1061.

    PubMed  CAS  Google Scholar 

  38. Balague C, Audie JP, Porchet N, et al. In situ hybridization shows distinct patterns of mucin gene expression in normal, benign, and malignant pancreas tissues. Gastroenterology 1995;109:953–964.

    Article  PubMed  CAS  Google Scholar 

  39. Yonezawa S, Horinouchi M, Osako M, et al. Gene expression of gastric type mucin (MUC5AC) in pancreatic tumors: its relationship with the biological behavior of the tumor. Pathol Int 1999;49:45–54.

    Article  PubMed  CAS  Google Scholar 

  40. Terris B, Dubois S, Buisine MP, et al. Mucin gene expression in intraductal papillary-mucinous pancreatic tumours and related lesions. J Pathol 2002;197:632–637.

    Article  PubMed  CAS  Google Scholar 

  41. Kocer B, Soran A, Erdogan S, et al. Expression of MUC5AC in colorectal carcinoma and relationship with prognosis. Pathol Int 2002;52:470–477.

    Article  PubMed  CAS  Google Scholar 

  42. Baldus SE, Monig SP, Arkenau V, et al. Correlation of MUC5AC immunoreactivity with histopathological subtypes and prognosis of gastric carcinoma. Ann Surg Oncol 2002;9:887–893.

    Article  PubMed  Google Scholar 

  43. Bartman AE, Buisine MP, Aubert JP, et al. The MUC6 secretory mucin gene is expressed in a wide variety of epithelial tissues. J Pathol 1998;186:398–405.

    Article  PubMed  CAS  Google Scholar 

  44. Lee HS, Lee HK, Kim HS, et al. MUC1, MUC2, MUC5AC, and MUC6 expressions in gastric carcinomas: their roles as prognostic indicators. Cancer 2001;92:1427–1434.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Wataru Kimura MD.

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This study was supported in part by the Japan-China Sasakawa Medical Fellowship.

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Jinfeng, M., Kimura, W., Hirai, I. et al. Expression of MUC5AC and MUC6 in invasive ductal carcinoma of the pancreas and relationship with prognosis. Int J Gastrointest Canc 34, 9–18 (2003). https://doi.org/10.1385/IJGC:34:1:09

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