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Correlation of MUC5AC immunoreactivity with histopathological subtypes and prognosis of gastric carcinoma

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Abstract

Background

MUC5AC represents a mucin peptide core expressed in normal gastric epithelia. Its presence in gastric carcinomas was previously described as a characteristic of gastric differentiation.

Methods

MUC5AC reactivity was investigated by immunohistochemistry and correlated with clinicopathological variables in a large series (n=200) of gastric carcinomas.

Results

A statistically significant association between MUC5AC positivity and parameters of cancer progression (pTNM staging and grading) could not be observed. However, MUC5AC exhibited correlations with certain subtypes of histopathological differentiation. A significant reduction of MUC5AC expression was evident in mucinous and undifferentiated carcinomas according to the World Health Organization classification, as well as in type III cancers according to the Goseki classification system. Furthermore, reduced MUC5AC reactivity (confined to up to 35% of the tumor area) was significantly correlated with an unfavorable prognosis of all patients in univariate and multivariate analysis. The same association could be observed in the subgroup of pTNM stage I patients (n=60).

Conclusions

A significant reduction of gastric differentiation as reflected by MUC5AC immunoreactivity represents a marker of worse survival probability in gastric cancer. Finally, reduced MUC5AC positivity defines a high-risk subgroup of pTNM stage I patients.

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References

  1. Baldus SE, Hanisch FG. Biochemistry and pathological importance of mucin-associated antigens in gastrointestinal neoplasia.Adv Cancer Res 2000;79:201–48.

    Article  PubMed  CAS  Google Scholar 

  2. Corfield AP, Carroll D, Myerscough N, Probert CS. Mucins in the gastrointestinal health and disease.Front Biosci 2001;6:D1321–57.

    PubMed  CAS  Google Scholar 

  3. Guyonnet Duperat V, Audié JP, Debailleur V, et al. Characterization of the human mucin gene MUC5AC: a consensus cysteinerich domain for 11p15 mucin genes?Biochem J 1995;305:211–9

    PubMed  Google Scholar 

  4. Ho SB, Roberton AM, Shekels LL, Lyftogt CT, Niehans GA, Toribara NW. Expression cloning of gastric mucin complementary DNA and localization of mucin gene expression.Gastroenterology 1995;109:735–47.

    Article  PubMed  CAS  Google Scholar 

  5. 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 1998;75:767–73.

    Article  PubMed  CAS  Google Scholar 

  6. Bara J, Loisillier F, Burtin P. Antigens of gastric and intestinal mucous cells in human colonic tumors.Br J Cancer 1980;41:209–21.

    PubMed  CAS  Google Scholar 

  7. 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;48:1657–65.

    PubMed  CAS  Google Scholar 

  8. Taylor KL, Mall AS, Barnard RA, Ho SB, Cruse JP. Immunohistochemical detection of gastric mucin in normal and disease states.Oncol Res 1998;10:465–73.

    PubMed  CAS  Google Scholar 

  9. Van den Brink GR, Tytgat KM, Van der Hulst RW, et al.. H pylori colocalises with MUC5AC in the human stomach.Gut 2000;46: 601–7.

    Article  PubMed  Google Scholar 

  10. Boren T, Falk P, Roth KA, Larson G, Normark S. Attachment of Helicobacter pylori to human gastric epithelium mediated by blood group antigensScience 1993;262:1892–5.

    Article  PubMed  CAS  Google Scholar 

  11. López-Ferrer A, Barranco C, de Bolós C. Apomucin expression and association with Lewis antigens during gastric development.Appl Immunohistochem Mol Morphol 2001;9:42–8.

    PubMed  Google Scholar 

  12. Reis CA, David L, Correa P, et al. Intestinal metaplasia of human stomach displays distinct patterns of mucin (MUC1, MUC2, MUC5AC, and MUC6) expression.Cancer Res 1999;59:1003–7.

    PubMed  CAS  Google Scholar 

  13. Carrato C, Balagué C, de Bolos, C, et al. Differential apomucin expression in normal and neoplastic human gastrointestinal tissues.Gastroenterology 1994;107:160–72.

    Google Scholar 

  14. Ho SB, Shekels LL, Toribara NW, Kim YS, Lyftogt C, Cherwitz DL, Niehans GA. Mucin gene expression in normal, pre-neoplastic and neoplastic human gastric epithelium.Cancer Res 1995;55: 2681–90.

    PubMed  CAS  Google Scholar 

  15. Reis CA, David L, Nielsen PA, et al. Immunohistochemical study of MUC5AC expression in human gastric carcinomas using a novel monoclonal antibody.Int J Cancer 1997;74:112–21

    Article  PubMed  CAS  Google Scholar 

  16. Machado JC, Nogueira AMMF, Carneiro F, Reis CA, Sobrinho-Simoes 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 2000;190:437–43.

    Article  PubMed  CAS  Google Scholar 

  17. Reis CA, 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 2000;48:377–88.

    PubMed  CAS  Google Scholar 

  18. Sobin LH, Wittekind C.TNM Classification of Malignant Tumors. 5th ed. New York: Miley, 1997.

    Google Scholar 

  19. Watanabe H, Jass JR, Sobin LH.Histological Typing of Oesophageal and Gastric Tumors. 2nd ed. Berlin: Springer, 1990.

    Google Scholar 

  20. Laurén P. The two main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma.Acta Pathol Microbiol Scand 1965:64:31–49.

    PubMed  Google Scholar 

  21. Goseki N, Takizawa T, Koike M. Differences in the mode of the extension of gastric cancer classified by histological type: new histological classification of gastric carcinoma.Gut 1992;33:606–12.

    PubMed  CAS  Google Scholar 

  22. Baldus SE, Zirbes TK, 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 1998;79:133–8.

    Article  PubMed  CAS  Google Scholar 

  23. Kaplan EL, Meier J. Nonparametric estimations from incomplete observations.J Am Assoc Stat 1958;53:457–81.

    Article  Google Scholar 

  24. Cox DR. Regression models and life tables (with discussion).J R Stat Soc B 1972;34:187–202.

    Google Scholar 

  25. Gürbüz Y, Kahlke V, Klöppel G. How do gastric carcinoma classification systems relate to mucin expression patterns? An immunohistochemical analysis in a series of advanced gastric carcinomas.Virchows Arch 2002;440:505–11.

    Article  PubMed  CAS  Google Scholar 

  26. Borchard F. Classification of gastric carcinoma.Hepatogastroenterology 1990;37:223–32.

    PubMed  CAS  Google Scholar 

  27. 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.Virchows Arch 2002;440:304–10.

    Article  PubMed  CAS  Google Scholar 

  28. Utsunomiya T, Yonezawa S, Sakamoto H, et al. Expression of MUC1 and MUC2 mucins in gastric carcinomas: its relationship with the prognosis of the patients.Clin Cancer Res 1998;4:2605–14.

    PubMed  CAS  Google Scholar 

  29. Sakamoto, Yonezawa S, Utsunomiya T, Tanaka S, Kim YS, Sato E. Mucin antigen expression in gastric carcinomas of young and old adults.Hum Pathol 1997;28:1056–65.

    Article  PubMed  CAS  Google Scholar 

  30. Baldus SE, Zirbes TK, Glossmann J, et al. Immunoreactivity of monoclonal antibody BW835 represents a marker of progression and prognosis in early gastric cancer.Oncology 2001;61:147–55.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Stephan E. Baldus MD.

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Baldus, S.E., Mönig, S.P., Arkenau, V. et al. Correlation of MUC5AC immunoreactivity with histopathological subtypes and prognosis of gastric carcinoma. Annals of Surgical Oncology 9, 887–893 (2002). https://doi.org/10.1007/BF02557526

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  • DOI: https://doi.org/10.1007/BF02557526

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