Skip to main content
NCBI home page
Journal of Cellular and Molecular Medicine logoLink to Journal of Cellular and Molecular Medicine
. 2007 May 1;5(3):327–351. doi: 10.1111/j.1582-4934.2001.tb00169.x

Altered mucin expression in the gastrointestinal tract: a review

J R Jass 1,✉, M D Walsh 2
PMCID: PMC6517815  PMID: 12067494

Abstract

Early studies of changes in mucin expression in disorders of the gastrointestinal tract focused on alterations in the carbohydrate chain. This review briefly considers the various mechanisms by which such alterations may come about: (a) normal variation, (b) sialic acid alterations, (c) defective assembly of carbohydrate side‐chains, (d) changed expression of core proteins and (e) epithelial metaplasia. The availability of monoclonal antibodies to mucin core proteins adds a new dimension to mucin histochemistry. It is now possible to offer explanations for traditional mucin histochemical findings on the basis of lineage‐specific patterns of mucin core protein expression. Changes in core protein expression are described in inflammatory, metaplastic and neoplastic disorders of the gastrointestinal tract. The possibility that mucin change could be important in the aetiology of some diseases such as ulcerative colitis and H. pylori gastritis is considered. It is more probable, however, that changes in mucin expression are secondary to reprogramming of cellular differentiation and altered cell turnover. As such they may serve as markers to explain pathogenesis and provide novel diagnostic and prognositc information.

Keywords: mucin, gastrointinal tract, histochemistry, differentiation, metaplasia, neoplasia, polyps, sialic acid, Helicobacter pylori

References

  • 1. Podolsky D.K., Oligosaccharide structures of human colonic mucin., J. Biol. Chem., 260: 8262–71, 1985. [PubMed] [Google Scholar]
  • 2. Podolsky D.K., Oligosaccharide structures of isolated human colonic mucin species., J. Biol. Chem., 260: 15510–15, 1985. [PubMed] [Google Scholar]
  • 3. Slomiany B.L., Murty V.L.N., Slomiany A., Isolation and characterization of oligosaccharides from rat colonic mucus glycoprotein, J. Biol. Chem., 255: 9719–23, 1980. [PubMed] [Google Scholar]
  • 4. Jass J.R., Roberton A.M., Colorectal mucin histochemistry in health and disease: A critical review., Pathol. Int., 44: 487–504, 1994. [DOI] [PubMed] [Google Scholar]
  • 5. Feizi T., Gooi H.C., Childs R.A. et al, Tumourassociated and differentiation antigens on the carbohydrate moieties of mucin‐type glycoproteins, Biochem. Soc. Trans., 12: 591–96, 1984. [DOI] [PubMed] [Google Scholar]
  • 6. Picard J.K., Feizi T., Peanut lectin and anti‐li antibodies reveal structural differences among human gastrointestinal glycoproteins, Mol. Immunol., 20: 1215–20, 1983. [DOI] [PubMed] [Google Scholar]
  • 7. Campbell B.J., Finnie I.A., Hounsell E.F., Rhodes J.M., Direct demonstration of increased expression of Thomsen‐Friedenreich (TF) antigen in colonic adenocarcinoma and ulcerative colitis mucin and its concealment in normal mucin., J. Clin. Invest., 95: 571–76, 1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8. Ørntoft T.F., Langkilde N.C., Wiener H., Ottosen P.D., Cellular localization of PNA binding in colorectal adenomas: Comparison with differentiation, nuclear: cell height ratio and effect of desialylation, APMIS, 99: 275–81, 1991. [DOI] [PubMed] [Google Scholar]
  • 9. Boland C.R., Montgomery C.K., Kim Y.S., Alterations in human colonic mucin occurring with cellular differentiation and malignant transformation, Proc. Natl. Acad. Sci. USA, 79: 2051–55, 1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10. Boland C.R., Montgomery C.K., Kim Y.S., A cancer‐associated mucin alteration in benign colonic polyps, Gastroenterology, 82: 664–72, 1982. [PubMed] [Google Scholar]
  • 11. Ørntoft T.F., Mors N.P.O., Eriksen G., Jacobsen N.O., Poulsen H.S., Comparative immunoperoxidase demonstration of T‐antigens in human colorectal carcinoma and morphologically abnormal mucosa, Cancer Res., 45: 447–52, 1985. [PubMed] [Google Scholar]
  • 12. Ørntoft T.F., Harving N., Langkilde N.C., O‐linked mucin‐type glycoproteins in normal and malignant colon mucosa: lack of T‐antigen expression and accumulation of Tn and sialosyl‐Tn antigens in carcinomas, Int. J. Cancer, 45: 666–72, 1990. [DOI] [PubMed] [Google Scholar]
  • 13. Hanski C., Hanisch F.G., Riecken E.O., Alteration of mucin‐bound carbohydrate moieties in malignant transformation of colonic mucosa, Cancer J., 5: 332–42, 1992. [Google Scholar]
  • 14. Dabelsteen E., Graem N., Clausen H., Hakomori S.‐I., Structural variations of blood group A antigens in human normal colon and carcinomas., Cancer Res., 48: 181–7, 1988. [PubMed] [Google Scholar]
  • 15. Henry S., Oriol F., Samuelson B., Lewis histoblood group system and associated secretory phenotypes., Vox. Sang., 69: 166–82, 1995. [DOI] [PubMed] [Google Scholar]
  • 16. Yuan M., Itzkowitz S.H., Palekar A. et al, Distribution of blood group antigens A, B, H, Lewisa, and Lewisb in human normal, fetal, and malignant colonic tissue, Cancer Res., 45: 4499–511, 1985. [PubMed] [Google Scholar]
  • 17. Holmes E.H., Ostrander G.K., Hakamori S., Biosynthesis of the sialyl‐SLex determinant carried by type two chain glycosphingolipids in human lung carcinoma PC9 cells, J. Biol. Chem., 261: 3737–43, 1986. [PubMed] [Google Scholar]
  • 18. Ajioka Y., Xing P.‐X., Hinoda Y., Jass J.R., Correlative histochemical study providing evidence for the dual nature of human colorectal cancer mucin, Histochem. J., 29: 143–52, 1997. [DOI] [PubMed] [Google Scholar]
  • 19. López‐Ferrer A., de Bolós C., Barranco C. et al, Role of fucosyltransferases in the association between apomucin and Lewis antigen expression in normal and malignant gastric epithelium, Gut, 47: 349–56, 2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20. Culling C.F.A., Reid P.E., Dunn W.L., A new histochemical method for the identification and visualisation of both side chain acylated and nonacylated sialic acids., J. Histochem. Cytochem., 24: 1225–30, 1976. [DOI] [PubMed] [Google Scholar]
  • 21. Hanski C., Bornhoeft G., Topf N. et al, Detection of a mucin marker for the adenoma‐carcinoma sequence in human colonic mucosa by monoclonal antibody AM‐3, J. Clin. Pathol., 43: 379–84, 1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22. Jass J.R., Allison L.J., Edgar S.G., Distribution of sialosyl Tn and Tn antigens within normal and malignant colorectal epithelium., J. Pathol., 176: 143–49, 1995. [DOI] [PubMed] [Google Scholar]
  • 23. Pilbrow S.J., Hertzog P.J., Linnane A.W., The adenoma‐carcinoma sequence in the colorectum ‐ early appearance of a hierarchy of small intestinal mucin antigen (SIMA) epitopes and correlation with malignant potential, Br. J. Cancer, 66: 748–57, 1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24. Richman P.I., Bodmer W.F., Monoclonal antibodies to human colorectal epithelium: markers for differentiation and tumour characterization, Int. J. Cancer., 39: 317–28, 1987. [DOI] [PubMed] [Google Scholar]
  • 25. Hughes N.R., Walls R.S., Newland R.C., Payne J.E., Gland to gland heterogeneity in histologically normal mucosa of colon cancer patients demonstrated by monoclonal antibodies to tissuespecific antigens, Cancer Res., 46: 5993–99, 1986. [PubMed] [Google Scholar]
  • 26. Hughes N.R., Walls R.S., Newland R.C., Payne J.E., Antigen expression in normal and neoplastic colonic mucosa: three tissue‐specific antigens using monoclonal antibodies to isolated colonic glands, Cancer Res., 46: 2164–71, 1986. [PubMed] [Google Scholar]
  • 27. Milton J.D., Eccleston D., Parker N. et al, Distribution of O‐acetylated sialomucin in the normal and diseased gastrointestinal tract shown by a new monoclonal antibody, J. Clin. Pathol., 46: 323–29, 1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28. Sugihara K., Jass J.R., Colorectal goblet cell sialomucin heterogeneity: its relation to malignant disease, J. Clin. Pathol., 39: 1088–95, 1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29. Campbell F., Appleton M.A., Fuller C.E. et al, Racial variation in the O‐acetylation phenotype of human colonic mucosa, J. Pathol., 174: 169–74, 1994. [DOI] [PubMed] [Google Scholar]
  • 30. Ogata S., Ho I., Chen A. et al, Tumor‐associated sialylated antigens are constitutively expressed in normal human colonic mucosa., Cancer Res., 55: 1869–74, 1995. [PubMed] [Google Scholar]
  • 31. Jass J.R., Allison L.M., Edgar S., Monoclonal antibody TKH2 to the cancer‐associated epitope sialosyl Tn shows cross‐reactivity with variants of normal colorectal goblet cell mucin., Pathology, 26: 418–22, 1994. [DOI] [PubMed] [Google Scholar]
  • 32. Filipe M.I., Mucins in the human gastrointestinal epithelium: a review, Invest. Cell Pathol., 2: 195–216, 1979. [PubMed] [Google Scholar]
  • 33. Hutchins J.T., Reading C.L., Giavazzi R., Hoaglund J., Jessup J.M., Distribution of mono‐, di‐, and tri‐O‐acetylated sialic acids in normal and neoplastic colon, Cancer Res., 48: 483–89, 1988. [PubMed] [Google Scholar]
  • 34. Hertzog P.J., Pilbrow S.J., Pedersen J. et al, Aberrant expression of intestinal mucin antigens associated with colorectal carcinoma defined by a panel of monoclonal antibodies, Br. J. Cancer, 64: 799–808, 1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35. Isaacson P., Attwood P.R.A., Failure to demonstrate specificity of the morphological and histochemical changes in mucosa adjacent to colonic carcinoma (transitional mucosa). J. Clin. Pathol., 32: 214–8, 1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36. Buisine M.P., Janin A., Maunoury V. et al, Aberrant expression of a human mucin gene (MUC5AC) in rectosigmoid villous adenoma, Gastroenterology, 110: 84–91, 1996. [DOI] [PubMed] [Google Scholar]
  • 37. Longman R.J., Douthwaite J., Sylvester P. et al, Lack of mucin MUC5AC field change expression associated with tubulovillous and villous colorectal adenomas, J. Clin. Pathol., 53: 100–04, 2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38. Itzkowitz S.H., Yuan M., Fukushi Y. et al, Lewisx‐ and sialylated lewisx‐related antigen expression in human malignant and nonmalignant colonic tissues, Cancer Res., 46: 2627–32, 1986. [PubMed] [Google Scholar]
  • 39. Yuan M., Itzkowitz S.H., Ferrell L.D. et al, Expression of lewisx and sialylated lewisx antigens in human colorectal polyps, J. Natl. Cancer Inst., 78: 479–88, 1987. [PubMed] [Google Scholar]
  • 40. Itzkowitz S.H., Bloom E.J., Lau T.‐S., Kim Y.S., Mucin associated Tn and sialosyl‐Tn antigen expression in colorectal polyps, Gut, 33: 518–23, 1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 41. Ito H., Hiraiwa N., Sawada‐Kasugai M. et al, Altered mRNA expression of specific molecular species of fucosyl‐ and sialyl‐ transferases in human colorectal cancer tissues, Int. J. Cancer, 71: 556–64, 1997. [DOI] [PubMed] [Google Scholar]
  • 42. Matsuura N., Narita T., Hiraiwa N. et al, Gene expression of fucosyl‐ and sialyl‐transferases which synthesize sialyl Lewisx, the carbohydrate ligands for E‐selectin, in human breast cancer, Int. J. Oncol., 12: 1157–64, 1998. [DOI] [PubMed] [Google Scholar]
  • 43. Laurén P., The two histological main types of gastric carcinoma: diffuse and so‐called intestinaltype carcinoma. An attempt at a histoclinical classification, Acta. Pathol. Microbiol. Scand., 64: 31–49, 1965. [DOI] [PubMed] [Google Scholar]
  • 44. Jass J.R., Smith M., Sialic acid and epithelial differentiation in colorectal polyps and cancer ‐ a morphological, mucin and lectin histochemical study, Pathology, 24: 233–42, 1992. [DOI] [PubMed] [Google Scholar]
  • 45. Tytgat K.M., van der Wal J.W., Einerhand A.W., Buller H.A., Dekker J., Quantitative analysis of MUC2 synthesis in ulcerative colitis, Biochem. Biophys. Res. Commun., 224: 397–405, 1996. [DOI] [PubMed] [Google Scholar]
  • 46. Chang S.‐K., Dohrman A.F., Basbaum C.B. et al, Localization of mucin (MUC2 and MUC3) messenger RNA and peptide expression in human normal intestine and colon cancer., Gastroenterology, 107: 28–36, 1994. [DOI] [PubMed] [Google Scholar]
  • 47. Hanski C., Born M., Foss H. D. et al, Defective post‐transcriptional processing of MUC2 mucin in ulcerative colitis and in Crohn's disease increases detectability of the MUC2 protein core, J. Pathol., 188: 304–11, 1999. [DOI] [PubMed] [Google Scholar]
  • 48. Podolsky D.K., Isselbacher K.J., Composition of human colonic mucin. Selective alterations in inflammatory bowel disease., J. Clin. Invest., 72: 142–53, 1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 49. Raouf A., Parker N., Iddon D. et al, Ion exchange chromatography of purified colonic mucus glycoproteins in inflammatory bowel disease: absence of a selective subclass defect, Gut, 32: 1139–45, 1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 50. Jass J.R., Sugihara K., Love S.B., Basis of sialic acid heterogeneity in ulcerative colitis, J. Clin. Pathol., 41: 388–92, 1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 51. Williams S.J., McGuckin M.A., Gotley D.C. et al, Two novel mucin genes down‐regulated in colorectal cancer identified by differential display, Cancer Res., 59: 4083–89, 1999. [PubMed] [Google Scholar]
  • 52. Kyo K., Parkes M., Takei Y. et al, Association of ulcerative colitis with rare VNTR alleles of the human intestinal mucin gene, MUC3, Hum. Mol. Genet., 8: 307–11, 1999. [DOI] [PubMed] [Google Scholar]
  • 53. Itzkowitz S.H., Young E., Dubois D. et al, Sialosyl‐Tn antigen is prevalent and precedes dysplasia in ulcerative colitis: a retrospective casecontrol study, Gastroenterology, 110: 694–704, 1996. [DOI] [PubMed] [Google Scholar]
  • 54. Kushima R., Hattori T., Okabe H., Borchard F., Stolte M., A histogenetic continuum of ulcerative colitis related lesions as revealed by immunohistochemistry for MUC2, MUC5AC and MUC6 mucins, Pathol. Int., 50 (Suppl):A80, 2000. [Google Scholar]
  • 55. Shepherd N.A., Healey C.J., Warren B.F. et al, Distribution of mucosal pathology and an assessment of colonic phenotypic change in the pelvic ileal reservoir, Gut, 34: 101–05, 1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 56. Corfield A.P., Warren B.F., Bartolo D.C., Wagner S.A., Clamp J.R., Mucin changes in ileoanal pouches monitored by metabolic labelling and histochemistry, Br. J. Surg., 79: 1209–12, 1992. [DOI] [PubMed] [Google Scholar]
  • 57. Sylvester P.A., Walsh M.D., Myerscough N., et al., Alteration in mucin gene expression occurs as the mucosa of the ileoanal reservoir adapts, Gut, 42 (suppl):A91, 1998. [Google Scholar]
  • 58. Wright N.A., Pike C., Elia G., Induction of a novel epidermal growth factor‐secreting cell lineage by mucosal ulceration in human gastrointestinal stem cells, Nature, 343: 82–85, 1990. [DOI] [PubMed] [Google Scholar]
  • 59. Wright N.A., Poulsom R., Stamp G. W. et al, Epidermal growth factor (EGF/URO) induces expression of regulatory peptides in damaged human gastrointestinal tissues, J. Pathol., 162: 279–84, 1990. [DOI] [PubMed] [Google Scholar]
  • 60. Ahnen D.J., Poulsom R., Stamp G.W. et al, The ulcer‐associated cell lineage (UACL) reiterates the Brunner's gland differentiation programme but acquires the proliferative organization of the gastric gland, J. Pathol., 173: 317–26, 1994. [DOI] [PubMed] [Google Scholar]
  • 61. Wright N.A., Poulsom R., Stamp G. et al, Trefoil peptide gene expression in gastrointestinal epithelial cells in inflammatory bowel disease, Gastroenterology, 104: 12–20, 1993. [DOI] [PubMed] [Google Scholar]
  • 62. Dignass A., Lynch‐Devaney K., Kindon H., Thim L., Podolsky D.K., Trefoil peptides promote epithelial migration through a transforming growth factor beta‐independent pathway, J. Clin. Invest., 94: 376–83, 1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 63. Seib T., Blin N., Hilgert K. et al, The three human trefoil genes TFF1, TFF2, and TFF3 are located within a region of 55 kb on chromosome 21q22.3, Genomics, 40: 200–02, 1997. [DOI] [PubMed] [Google Scholar]
  • 64. Hanby A.M., Poulsom R., Singh S. et al, Spasmolytic polypeptide is a major antral peptide: distribution of the trefoil peptides human spasmolytic polypeptide and pS2 in the stomach, Gastroenterology, 105: 1110–16, 1993. [DOI] [PubMed] [Google Scholar]
  • 65. Podolsky D.K., Lynch‐Devaney K., Stow J.L. et al, Identification of human intestinal trefoil factor. Goblet cell‐specific expression of a peptide targeted for apical secretion, J. Biol. Chem., 268: 6694–702, 1993. [PubMed] [Google Scholar]
  • 66. Tomasetto C., Masson R., Linares J.L. et al, pS2/TFF1 interacts directly with the VWFC cysteine‐rich domains of mucins, Gastroenterology, 118: 70–80, 2000. [DOI] [PubMed] [Google Scholar]
  • 67. Longman R.J., Douthwaite J., Sylvester P.A. et al, Coordinated localisation of mucins and trefoil peptides in the ulcer associated cell lineage and the gastrointestinal mucosa, Gut, 47: 792–800, 2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 68. van Klinken B.J., Dekker J., van Gool S.A. et al, MUC5B is the prominent mucin in human gallbladder and is also expressed in a subset of colonic goblet cells, Am. J. Physiol., 274: G871–G78, 1998. [DOI] [PubMed] [Google Scholar]
  • 69. Roberts I.S., Stoddart R.W., Ulcer‐associated cell lineage (‘pyloric metaplasia’) in Crohn's disease: a lectin histochemical study, J. Pathol, 171: 13–19, 1993. [DOI] [PubMed] [Google Scholar]
  • 70. Spychal R.T., Goggin P.M., Marrero J.M. et al, Surface hydrophobicity of gastric mucosa in peptic ulcer disease: relationship to gastritis and Campylobacter pylori infection, Gastroenterology, 98: 1250–54, 1990. [DOI] [PubMed] [Google Scholar]
  • 71. Sidebotham R.L., Batten J.J., Karim Q.N., Spencer J., Baron J.H., Breakdown of gastric mucus in presence of Helicobacter pylori, J. Clin. Pathol., 44: 52–57, 1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 72. Newton J.L., Jordan N., Oliver L. et al, Helicobacter pylori in vivo causes structural changes in the adherent gastric mucus layer but barrier thickness is not compromised, Gut, 43: 470–75, 1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 73. Markesich D.C., Anand B.S., Lew G.M., Graham D.H., Helicobacter pylori infection does not reduce the viscosity of human gastric mucus gel, Gut, 36: 327–29, 1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 74. Byrd J.C., Yan P., Sternberg L. et al, Aberrant expression of gland‐type mucin in the surface epithelium of H. pylori‐infected patients, Gastroenterology, 113: 455–64, 1997. [DOI] [PubMed] [Google Scholar]
  • 75. Byrd J.C., Yunker C.K., Xu Q.S., Sternberg L.R., Bresalier R.S., Inhibition of gastric mucin synthesis by Helicobacter pylori, Gastroenterology, 118: 1–9, 2000. [DOI] [PubMed] [Google Scholar]
  • 76. Rieder G., Moran A.P., Walz A., Stolte M., Enders G., Role of adherence in interleukin‐8 induction in Helicobacter pylori‐associated gastritis, Infect. Immun., 65: 3622–30, 1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 77. Dixon M.F., Recent advances in gastritis, Curr. Diag. Pathol., 1: 80–89, 1994. [Google Scholar]
  • 78. Sobala G.M., O'Connor H.J., Dewar E.P., et al, Bile reflux and intestinal metaplasia of gastric mucosa, J. Clin. Pathol., 46: 235–40, 1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 79. Reis C.A., David L., Correa P., et al, Intestinal metaplasia of human stomach displays distinct patterns of mucin (MUC1, MUC2, MUC5AC, and MUC6) expression, Cancer Res., 59: 1003–07, 1999. [PubMed] [Google Scholar]
  • 80. Jass J.R., Role of intestinal metaplasia in the histogenesis of gastric carcinoma, J. Clin. Pathol., 33: 801–10, 1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 81. Filipe M.I., Potet F., Bogomoletz W.V., et al, Incomplete sulphomucin‐secreting intestinal metaplasia. Preliminary data from a prospective study from three centres, Gut, 26: 1319–26, 1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 82. Craanen M.E., Blok P., Dekker W., Ferwerda J., Tytgat G.N.J., Prevalence of subtypes of intestinal metaplasia in gastric antral mucosa, Dig. Dis. Sci., 36: 1529–36, 1991. [DOI] [PubMed] [Google Scholar]
  • 83. Sipponen P., Seppala K., Varis K., et al, Intestinal metaplasia with colonic‐type sulphomucins in the gastric mucosa; its association with gastric carcinoma, Acta. Pathol. Microbiol. Scand., 88: 217–24, 1980. [DOI] [PubMed] [Google Scholar]
  • 84. Genta R.M., Gürer I.C., Graham D.Y., et al, Adherence of Helicobacter pylori to areas of incomplete intestinal metaplasia in the gastric mucosa, Gastroenterology, 111: 1206–11, 1996. [DOI] [PubMed] [Google Scholar]
  • 85. Thompson J.J., Zinsser K.R., Enterline H.T., Barrett's metaplasia and adenocarcinoma of the esophagus and gastroesophageal junction, Hum. Pathol., 14: 42–61, 1983. [DOI] [PubMed] [Google Scholar]
  • 86. Paull A., Trier J.S., Dalton M.D., et al, The histologic spectrum of Barrett's esophagus, N. Eng. J. Med., 295: 476–80, 1976. [DOI] [PubMed] [Google Scholar]
  • 87. Haggitt R.C., Tryzelaar J., Ellis F.H., Colcher H., Adenocarcinoma complicating columnar epithelium‐lined (Barrett's) esophagus, Am. J. Clin. Pathol., 70: 1–5, 1978. [DOI] [PubMed] [Google Scholar]
  • 88. Reid B.J., Weinstein W.M., Barrett's esophagus and adenocarcinoma, Annu. Rev. Med., 38: 477–92, 1987. [DOI] [PubMed] [Google Scholar]
  • 89. Chandrasoma P.T., Lokuhetty D.M., Demeester T.R., et al, Definition of histopathologic changes in gastroesophageal reflux disease, Am. J. Surg. Pathol., 24: 344–51, 2000. [DOI] [PubMed] [Google Scholar]
  • 90. Takubo K., Sasajima K., Yamashita K., Tanaka Y., Fujita K., Double muscularis mucosae in Barrett's esophagus, Hum. Pathol., 22: 1158–61, 1991. [DOI] [PubMed] [Google Scholar]
  • 91. Voutilainen M., Farkkila M., Juhola M., Meckin J.P., Sipponen P., Complete and incomplete intestinal metaplasia at the oesophagogastric junction: prevalences and associations with endoscopic erosive eosophagitis and gastritis, Gut, 45: 644–48, 1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 92. Arul G.S., Moorghen M., Myerscough N., et al, Mucin gene expression in Barrett's oesophagus: an in situ hybridisation and immunohistochemical study, Gut, 47: 753–61, 2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 93. Labouvie C., Machado J.C., Carneiro F., et al, Differential expression of mucins and trefoil peptides in native epithelium, Barrett's metaplasia and squamous cell carcinoma of the oesophagus, J. Cancer Res. Clin. Oncol., 125: 71–76, 1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 94. Guillem P., Billeret V., Buisine M.‐P., et al, Mucin gene expression and cell differentiation in human normal, premalignant and malignant esophagus, Int. J. Cancer, 88: 856–61, 2000. [DOI] [PubMed] [Google Scholar]
  • 95. Jass J.R., Mucin histochemistry of the columnar epithelium of the oesophagus. A retrospective study., J. Clin. Pathol., 34: 866–87, 1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 96. Duchatelle V., Potet F., Bara J., Ma J., Goldfain D., Mucin immunohistochemistry of the columnar epithelium, Virchows Arch., 414: 359–63, 1989. [DOI] [PubMed] [Google Scholar]
  • 97. Li H., Walsh W.H., O'Dowd G., et al, Mechanisms of columnar metaplasia and squamous regeneration in experimental Barrett's esophagus, Endoscopy, 2: 121–26, 1994. [PubMed] [Google Scholar]
  • 98. Ormsby A.H., Goldblum J.R., Rice T.W., et al, Cytokeratin subsets can reliably distinguish Barrett's esophagus from intestinal metaplasia of the stomach, Hum. Pathol., 30: 288–94, 1999. [DOI] [PubMed] [Google Scholar]
  • 99. Namiot Z., Sarosiek J., Rourk R.M., Hetzel D.P., McCallum R.W., Human esophageal secretion: mucosal response to luminal acid and pepsin, Gastroenterology, 106: 973–81, 1994. [DOI] [PubMed] [Google Scholar]
  • 100. Hanby A.M., Jankowski J.A., Elia G., Poulsom R., Wright N.A., Expression of the trefoil peptides pS2 and human spasmolytic polypeptide (hSP) in Barrett's metaplasia and the native oesophageal epithelium: delineation of epithelial phenotype, J. Pathol., 173: 213–19, 1994. [DOI] [PubMed] [Google Scholar]
  • 101. Eads C.A., Lord R.V., Kurumboor S.K., et al, Fields of aberrant CpG island hypermethylation in Barrett's esophagus and associated adenocarcinoma, Cancer Res., 60: 5021–26, 2000. [PubMed] [Google Scholar]
  • 102. Carneiro F., Seixas M., Sobrinho‐Simões M., New elements for an updated classification of the carcinomas of the stomach, Path. Res. Pract., 191: 571–84, 1995. [DOI] [PubMed] [Google Scholar]
  • 103. Hattori T., Development of adenocarcinoma in the stomach, Cancer, 57: 1528–34, 1986. [DOI] [PubMed] [Google Scholar]
  • 104. Egashira Y., Shimoda T., Ikegami M., Mucin histochemical analysis of minute gastric differentiated adenocarcinoma, Pathol. Int., 49: 55–61, 1999. [DOI] [PubMed] [Google Scholar]
  • 105. Schlemper R.J., Itabashi M., Kato Y., et al, Differences in diagnostic criteria for gastric carcinoma between Japanese and Western pathologists, Lancet, 349: 1725–29, 1997. [DOI] [PubMed] [Google Scholar]
  • 106. Lauwers G.Y., Shimizu M., Correa P., et al, Evaluation of gastric biopsies for neoplasia. Differences between Japanese and Western pathologists, Am. J. Surg. Pathol., 23: 511–18, 1999. [DOI] [PubMed] [Google Scholar]
  • 107. Kabashima A., Yao T., Sugimachi K., Tsuneyoshi M., Gastric or intestinal phenotypic expression in the carcinomas and background mucosa of multiple early gastric carcinomas, Histopathology, 37: 513–22, 2000. [DOI] [PubMed] [Google Scholar]
  • 108. Wang Y.‐Z., Mitomi H., Kurihara M., et al, Gastric adenomas and superficial adenocarcinomas display distinct patterns of mucin carbohydrate and core protein expression, Histopathology, 17: 250–59, 2000. [DOI] [PubMed] [Google Scholar]
  • 109. Endoh Y., Tamura G., Ajioka Y., Watanabe H., Motoyama T., Frequent hypermethylation of the hMLHl gene promoter in differentiated‐type tumors of the stomach with the gastric foveolar phenotype, Am. J. Pathol., 157: 717–22, 2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 110. Endoh Y., Tamura G., Motoyama T., Ajioka Y., Watanabe H., Well‐differentiated adenocarcinoma mimicking complete‐type intestinal metaplasia in the stomach, Hum. Pathol., 30: 826–32, 1999. [DOI] [PubMed] [Google Scholar]
  • 111. Endoh Y., Sakata K., Tamura G., et al, Cellular phenotypes of differentiated‐type adenocarcinomas and precancerous lesions of the stomach are dependent on the genetic pathways, J. Pathol., 191: 257–63, 2000. [DOI] [PubMed] [Google Scholar]
  • 112. Machado J.C., Nogueira A.M.M.F., Carneiro F., Reis C.A., Sobrinho‐Simões M., Gastric carcinoma exhibits distinct types of cell differentiation: an immunohistochemical study of trefoil peptides (TFF1 and TFF2) and mucins (MUC1, MUC2, MUC5AC and MUC6), J. Pathol., 190: 437–43, 2000. [DOI] [PubMed] [Google Scholar]
  • 113. Ajioka Y., Allison L.J., Jass J.R., Significance of MUC1 and MUC2 mucin expression in colorectal cancer., J. Clin. Pathol., 49: 560–64, 1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 114. Baldus S.E., Zirbes T.K., Engel S., et al, Correlation of the immunohistochemical reactivity of mucin peptide cores MUC1 and MUC2 with the histopathological subtype and prognosis of gastric carcinomas, Int. J. Cancer (Pred. Oncol.), 79: 133–38, 1998. [DOI] [PubMed] [Google Scholar]
  • 115. Reis C.A., David L., Carvalho F., et al, Immunohistochemical study of the expression of MUC6 mucin and co‐expression of other secreted mucins (MUC5AC and MUC2) in human gastric carcinomas, J. Histochem. Cytochem., 48: 377–88, 2000. [DOI] [PubMed] [Google Scholar]
  • 116. Jass J.R., Young J., Leggett B.A., Hyperplastic polyps and DNA microsatellite unstable cancers of the colorectum, Histopathology, 37: 295–301, 2000. [DOI] [PubMed] [Google Scholar]
  • 117. Ajioka Y., Watanabe H., Jass J.R., MUC1 and MUC2 mucins in flat and polypoid colorectal adenomas, J. Clin. Pathol., 50: 417–21, 1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 118. Blank M., Klussmann E., Kruger‐Krasagakes S., et al, Expression of MUC2‐mucin in colorectal adenomas and carcinomas of different histological types., Int. J. Cancer, 59: 301–06, 1994. [DOI] [PubMed] [Google Scholar]
  • 119. Biemer‐Hüttmann A.‐E., Walsh M.D., McGuckin M.A., et al, Immunohistochemical staining patterns of MUC1, MUC2, MUC4, and MUC5AC mucins in hyperplastic polyps, serrated adenomas, and traditional adenomas of the colorectum, J. Histochem. Cytochem., 47: 1039–47, 1999. [DOI] [PubMed] [Google Scholar]
  • 120. Bartman A.E., Sanderson S.J., Ewing S.I., et al, Aberrant expression of MUC5AC and MUC6 gastric mucin genes in colorectal polyps, Int. J. Cancer, 80: 210–18, 1999. [DOI] [PubMed] [Google Scholar]
  • 121. Yao T., Kouzuki T., Kajiwara M., et al, ‘Serrated’ adenoma of the colorectum, with reference to its gastric differentiation and its malignant potential, J. Pathol., 187: 511–17, 1999. [DOI] [PubMed] [Google Scholar]
  • 122. Bara J., Chastre E., Mahiou J., et al, Gastric M1 mucin, an early oncofetal marker of colon carcinogenesis is encoded by the MUC5AC gene, Int. J. Cancer, 75: 767–73, 1998. [DOI] [PubMed] [Google Scholar]
  • 123. Jass J.R., Iino H., Ruszkiewicz A., et al, Neoplastic progression occurs through mutator pathways in hyperplastic polyposis of the colorectum, Gut, 46:(in press),2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 124. Biemer‐Hüttmann A.‐E., Walsh M.D., McGuckin M.A., et al, Mucin core protein expression in colorectal cancers with high levels of microsatellite instability indicates a novel pathway of morphogenesis, Clin. Cancer Res., 6: 1909–16, 2000. [PubMed] [Google Scholar]
  • 125. Deng X., Bellis S., Yan Z., Friedman E., Differential responsiveness to autocrine and exogenous transforming growth factor (TGF) beta 1 in cells with nonfunctional TGF‐beta receptor type III, Cell Growth Differ., 10: 11–18, 1999. [PubMed] [Google Scholar]
  • 126. Goldman H., Ming S.‐C., Hickock D.F., Nature and significance of hyperplastic polyps of the human colon, Arch. Pathol., 89: 349–54, 1970. [PubMed] [Google Scholar]
  • 127. Jass J.R., Constable L., Sutherland R., et al, Adenocarcinoma of colon differentiating as dome epithelium of gut‐associated lymphoid tissue, Histopathology, 36: 116–20, 2000. [DOI] [PubMed] [Google Scholar]
  • 128. Agawa S., Jass J.R., Sialic acid histochemistry and the adenoma‐carcinoma sequence in colorectum., J. Clin. Pathol., 43: 528–32, 1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 129. Fang D.‐C., Jass J.R., Wang D.‐X., et al, Infrequent loss of heterozygosity of APC/MCC and DCC genes in gastric cancer showing DNA microsatellite instability, J. Clin. Pathol., 52: 504–08, 1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 130. Toyota M., Ahuja N., Ohe‐Toyota M., et al, CpG island methylator phenotype in colorectal cancer, Proc. Natl. Acad. Sci. USA, 96: 8681–86, 1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 131. Jackson‐Grusby L., Beard C., Possemato R., et al, Loss of genomic methylation causes p53‐ dependent apoptosis and epigenetic deregulation, Nature Genet., 27: 31–39, 2001. [DOI] [PubMed] [Google Scholar]
  • 132. Feinberg A.P., Vogelstein B., Hypomethylation distinguishes genes of some human cancers from their normal counterparts, Nature, 301: 89–92, 1983. [DOI] [PubMed] [Google Scholar]
  • 133. Hanski C., Riede E., Gratchev A., et al, MUC2 gene suppression in human colorectal carcinomas and their metastases: in vitro evidence of the modulatory role of DNA methylation, Lab. Invest., 77: 685–95, 1997. [PubMed] [Google Scholar]
  • 134. Devine P.L., McGuckin M.A., Birrell G.W., et al, Monoclonal antibodies reacting with the MUC2 mucin core protein, Br. J. Cancer, 67: 1182–88, 1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 135. Xing P.X., Prenzoska J., Apostolopoulos V., Karkaloutsos J., McKenzie I.F.C., Monoclonal antibodies to a MUC4 peptide react with lung cancer, Int. J. Oncol., 11: 289–95, 1997. [PubMed] [Google Scholar]
  • 136. Swallow D.M., Gendler S., Griffiths B., et al, The human tumour‐associated epithelial mucins are coded by an expressed hypervariable gene locus PUM, Nature, 328: 82–84, 1987. [DOI] [PubMed] [Google Scholar]
  • 137. Swallow D.M., Gendler S., Griffiths B., et al, The hypervariable gene locus PUM, which codes for the tumour associated epithelial mucins, is located on chromosome 1, within the region 1q21‐ 24, Ann. Hum. Genet., 51: 289–94, 1987. [DOI] [PubMed] [Google Scholar]
  • 138. Gum J.R., Hicks J.W., Toribara N.W., et al, The human MUC2 intestinal mucin has cysteine‐rich subdomains located both upstream and downstream of its central repetitive region., J. Biol. Chem., 267: 21375–83, 1992. [PubMed] [Google Scholar]
  • 139. Porchet N., van Chong N., Dufosse J., et al, Molecular cloning and chromosomal localisation of a novel human tracheo‐bronchial mucin cDNA containing tandemly repeated sequences of 48 base pairs., Biochem. Biophys. Res. Commun., 175: 414–22, 1991. [DOI] [PubMed] [Google Scholar]
  • 140. Moniaux N., Nollet S., Porchet N., et al, Complete sequence of the human mucin MUC4: a putative cell membrane‐ associated mucin, Biochem. J., 338: 325–33, 1999. [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Cellular and Molecular Medicine are provided here courtesy of Blackwell Publishing

RESOURCES