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Vol. 61, No. 3, 2001
Issue release date: September 2001
Oncology 2001;61:212–220
(DOI:10.1159/000055377)

Gastric and Intestinal Phenotypic Marker Expression in Gastric Carcinomas and Its Prognostic Significance: Immunohistochemical Analysis of 136 Lesions

Tajima Y. · Shimoda T. · Nakanishi Y. · Yokoyama N. · Tanaka T. · Shimizu K. · Saito T. · Kawamura M. · Kusano M. · Kumagai K.
aDepartment of Surgery, Toyosu Hospital, Showa University, bSecond Department of Surgery, Faculty of Medicine, Showa University, cClinical Laboratory Division, National Cancer Center Hospital, dPathology Division, National Cancer Center Research Institute, Tokyo, Japan

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Abstract

Objective: It is well known that both gastric and intestinal phenotypic cell markers are expressed in gastric carcinomas, irrespective of their histologic type. However, the clinicopathologic significance of these expressions has not yet been clarified. Methods: We analyzed the correlations among gastric and intestinal phenotypic marker expression patterns of the tumor, clinicopathologic findings and the patient’s outcome in 136 advanced gastric carcinomas. Results: Phenotypic marker expression was immunohistochemically evaluated using the monoclonal antibodies 45M1 (anti-human gastric mucin; HGM), CLH5 (anti-MUC6), Ccp58 (anti-MUC2) and 56C6 (anti-CD10). All tumors were classified as gastric (G), gastric and intestinal mixed (GI), intestinal (I) or unclassified (UC) phenotype. Of the 136 gastric carcinomas, 50 (36.8%), 56 (41.2%), 21 (15.4%) and 9 (6.6%) were classified as G, GI, I and UC phenotype, respectively. The G-phenotype tumors were associated with a higher rate of undifferentiated-type and infiltrative histology as compared with the I-phenotype tumors (p < 0.05 and p < 0.001, respectively). Furthermore, both univariate and multivariate analysis of survival revealed the G-phenotype tumor to be associated with a significantly poorer outcome than the I-phenotype tumor (p < 0.05). Conclusion: Our present results indicate that the gastric and intestinal phenotypic marker expression pattern of tumors, determined by the combination of HGM, MUC6, MUC2 and CD10 expression, is prognostically useful for patients with gastric carcinoma.



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References

  1. Nakamura K, Sugano H, Takagi K: Carcinoma of the stomach in incipient phase: Its histogenesis and histological appearances. Gann 1968;59:251–258.
  2. Lauren P: The two histological main types of gastric carcinoma: Diffuse and so-called intestinal-type carcinoma. Acta Pathol Microbiol Scand A 1965;64:31–49.
  3. Saito K, Shimoda T: Histogenesis and early invasion of gastric cancer. Acta Pathol Jpn 1986;36:1307–1318.

    External Resources

  4. Tahara E: Genetic alternations in human gastrointestinal cancers. Cancer 1995;75:1410–1417.
  5. Egashira Y, Shimoda T, Ikegami M: Mucin histochemical analysis of minute gastric differentiated adenocarcinoma. Pathol Int 1999;49:55–61.
  6. Sasaki I, Yao T, Nawata H, Tsuneyoshi M: Minute gastric carcinoma of differentiated type with special reference to the significance of intestinal metaplasia, proliferative zone, and p53 protein during tumor development. Cancer 1999;85:1719–1729.
  7. Yoshino T, Shimoda T, Saito A, Nakanishi Y, Tajima Y, Shirasu T, Miura S: Macroscopic features of differentiated adenocarcinoma with gastric or intestinal phenotype expression in early gastric cancer (in Japanese with English abstract). Stomach Intestine 1999;34:513–525.
  8. Endoh Y, Tamura G, Motoyama T, Ajioka Y, Watanabe H: Well-differentiated adenocarcinoma mimicking complete-type intestinal metaplasia in the stomach. Hum Pathol 1999;30:826–832.
  9. Endoh Y, Tamura G, Watanabe H, Ajioka Y, Motoyama T: The common 18-base pair deletion at codons 418–423 of the E-cadherin gene in differentiated-type adenocarcinomas and intramucosal precancerous lesions of the stomach with the features of gastric foveolar epithelium. J Pathol 1999;189:201–206.
  10. Machado JC, Nogueira AM, 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;190:437–443.
  11. Koseki K, Takizawa T, Koike M, Ito M, Nihei Z, Sugihara K: Distinction of differentiated type early gastric carcinoma with gastric type mucin expression. Cancer 2000;89:724–732.
  12. Tatematsu M, Ichinose M, Miki K, Hasegawa R, Kato T, Ito N: Gastric and intestinal phenotypic expression of human stomach cancers as revealed by pepsinogen immunohistochemistry and mucin histochemistry. Acta Pathol Jpn 1990;40:494–504.
  13. Tatematsu M, Furihata C, Katsuyama T, Miki K, Honda H, Konoshi Y, Ito N: Gastric and intestinal phenotypic expressions of human signet ring cell carcinomas revealed by their biochemistry, mucin histochemistry, and ultrastructure. Cancer Res 1986;46:4866–4872.

    External Resources

  14. Japanese Research Society for Gastric Cancer: Japanese Classification of Gastric Carcinoma, ed 1 (English). Tokyo, Kanehara, 1995.
  15. Bara J, Gautier R, Mouradian P, Decaens C, Daher N: Oncofetal mucin M1 epitope family: Characterization and expression during colonic carcinogenesis. Int J Cancer 1991;47:304–310.
  16. 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.
  17. Carvalho F, David L, Aubert JP, Lopez-Ferrer A, De Bolos C, Reis CA, Gartner F, Peixoto A, Alves P, Sobrinho-Simoes M: Mucins and mucin-associated carbohydrate antigens expression in gastric carcinoma cell lines. Virchows Arch 1999;435:479–485.
  18. Reis CA, David L, Correa P, Carneiro F, De Bolos C, Garcia E, Mandel U, Clausen H, Sobrinho-Simoes M: Intestinal metaplasia of human stomach displays distinct pattern of mucin (MUC1, MUC2, MUC5AC, and MUC6) expression. Cancer Res 1999;59:1003–1007.
  19. Gum JR, Byrd JC, Hicks JW, Toribara NW, Lamport DTA, Kim YS: Molecular cloning of human intestinal mucin cDNAs. J Biol Chem 1989;264:6480–6487.
  20. Kim YS, Gum JR: Diversity of mucin genes, structure, function, and expression. Gastroenterology 1995;109:999–1013.
  21. Baldus SE, Zirbes TK, Engel S, Hanisch FG, Monig SP, Lorenzen J, Glossmann J, Fromm S, Thiele J, Pichlmaier H, Dienes HP: 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;79:133–138.
  22. Sakamoto H, Yonezawa S, Utsunomiya T, Tanaka S, Kim YS, Sato E: Mucin antigen expression in gastric carcinomas of young and old adults. Hum Pathol 1997;28:1056–1065.
  23. Utsunomiya T, Yonezawa S, Sakamoto H, Kitamura H, Hokita S, Aiko T, Tanaka S, Irimura T, Kim YS, Sato E: Expression of MUC1 and MUC2 mucins in gastric carcinoma: Its relationship with the prognosis of the patients. Clin Cancer Res 1998;4:2605–2614.
  24. Ronco P, Allegri L, Melcion C, Pirotsky E, Appay MD, Bariety J, Pontillon F, Verroust P: A monoclonal antibody to brush border and passive Heymann nephritis. Clin Exp Immunol 1984;55:319–332.
  25. Trejdosiewicz LK, Malizia G, Oakes J, Losowsky MS, Janossy G: Expression of common acute lymphoblastic leukaemia antigen (CALLA gp100) in the brush border of normal jejunum and jejunum of patients with coeliac disease. J Clin Pathol 1985;38:1002–1006.

    External Resources

  26. Sato Y, Itoh F, Hinoda Y, Ohe Y, Nakagawa N, Ueda R, Yachi A, Imai K: Expression of CD10/neutral endopeptidase in normal and malignant tissues of the human stomach and colon. J Gastroenterol 1996;31:12–17.
  27. Hsu SM, Raine L, Fanger H: Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: A comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem 1981;29:577–580.
  28. Shi SR, Key ME, Karla KL: Antigen retrieval in formalin-fixed, paraffin-embedded tissues: An enhancement method for immunohistochemical staining based on microwave oven heating of tissue sections. J Histochem Cytochem 1991;39:741–748.
  29. Cox DR: Regression models and life tables. J R Soc Stat 1972;24:187.
  30. Kaplan EL, Meier P: Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;53:457–481.
  31. Peto R, Pike MC, Armitage P, Breslow NE, Cox DR, Howard SV, Mantel N, McPherson K, Peto J, Smith PG: Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. Analysis and examples. Br J Cancer 1977;35:1–39.
  32. Yamachika T, Inada K, Fijimitsu Y, Nakamura S, Yamamura Y, Kitou T, Itzkowitz SH, Werther JL, Miki K, Tatematsu M: Intestinalization of gastric signet ring cell carcinomas with progression. Virchows Arch 1997;431:103–110.
  33. Yoshikawa A, Inada K, Yamachika T, Shimizu N, Kaminishi M, Tatematsu M: Phenotypic shift in human differentiated gastric cancers from gastric to intestinal epithelial cell type during disease progression. Gastric Cancer 1998;1:134–141.

    External Resources



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