Digestive Diseases and Sciences

, Volume 47, Issue 3, pp 573–578 | Cite as

Identification of Spasmolytic Polypeptide Expressing Metaplasia (SPEM) in Remnant Gastric Cancer and Surveillance Postgastrectomy Biopsies

  • Hirokazu Yamaguchi
  • James R. Goldenring
  • Michio Kaminishi
  • Jeffrey R. Lee
Article

Abstract

Following gastrectomy, the remnant oxyntic mucosa is at increased risk of developing adenocarcinoma. Alkaline pancreaticoduodenal reflux, carcinogen production from intragastric bacterial overgrowth, denervation, and devascularization have been implicated in this malignant transformation. Recent reports have described a novel spasmolytic polypeptide (SP) expressing metaplastic lineage designated as SPEM. This lineage has been identified in the mucosa surrounding gastric adenocarcinomas, and SP staining has been observed in the cells of surface dysplasia and invasive malignancy. In this study we describe 19 cases of remnant gastric adenocarcinoma from Japan. In addition, we studied surveillance biopsies in 90 patients who underwent antrectomy for carcinoma. SPEM was identified in the mucosa surrounding 88% of the remnant cancers, as well as in 61% of the surveillance biopsies. In the malignant resections, 67% of the surface dysplasia displayed SP positive cells, and 25% revealed SP immunostaining within invasive malignant cells. These findings implicate SPEM as a potential precursor lesion of gastric adenocarcinoma.

remnant adenocarcinoma spasmolytic polypeptide SPEM intestinal metaplasia 

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REFERENCES

  1. 1.
    Termette AC, Offerhaus GJA, Tersmette KWF, Giardiello FM, Moore GW, Tytgat GNJ, Vandenbroucke JP: Metaanalysis of the risk of gastric stump cancer: Detection of high risk patient subsets for stomach cancer after remote partial gastrectomy for benign conditions. Cancer Res 50:6486–6489, 1990Google Scholar
  2. 2.
    Kaminishi M, Shimizu N, Shimoyama S, Yamaguchi H, Ogawa T, Sakai S, Kuramoto S, Oohara T: Etiology of gastric remnant cancer with special reference to the effects of denervation of the gastric mucosa. Cancer 75:1490–1496, 1995Google Scholar
  3. 3.
    Lewin KJ, Appleman HD: Non-neoplastic tumor-like lesions, predominantly epithelial. In Atlas of Tumor Pathology: Tumors of the Esophagus and Stomach. J. Rosai (ed). Washington, DC, Armed Forces Institute of Pathology, 1996, pp 224–228Google Scholar
  4. 4.
    Wang TC, Goldenring JR, Dangler C, Ito S, Mueller A, Jeon WK, Koh T, Fox JG: C57BL/6 mice deficient in secretory phospholipase A2 show increased apoptosis and altered cellular differentiation during Helicobacter felis infection. Gastroenterology 114:675–689, 1998Google Scholar
  5. 5.
    Schmidt PH, Lee JR, Joshi V, Playford RJ, Poulsom R, Wright NA, Goldenring JR: Identification of a metaplastic cell lineage associated with human gastric adenocarcinoma. Lab Invest 79:639–646, 1999Google Scholar
  6. 6.
    Vartanian RK, Leung JK, Davis JE, Kim YB, Owen DA: A novel Alcian yellow-toluidine blue (Leung) stain for Helicobacter species: Comparison with standard stains, a costeffectiveness analysis, and supplemental utilities. Mod Pathol 11:72–78, 1998Google Scholar
  7. 7.
    Peura DA: The report of the Digestive Health InitiativeSM International Update Conference on Helicobacter pylori. Gastroenterology 113:S4–S8, 1997Google Scholar
  8. 8.
    International Agency for Research of Cancer Monographs on the Evaluation of Carcinogenic Risk to Humans. Infection with Helicobacter pylori, Vol 61. Lyon, IARC 1994, pp. 177–240Google Scholar
  9. 9.
    Ritchie WP: Alkaline reflux gastritis: A critical reappraisal. Gut 25:975–987Google Scholar
  10. 10.
    Joossens JV, Geboers J: Diet and environment in the etiology of gastric cancer. In Frontiers of Gastrointestinal Cancer. B Lewin, RH Riddell (eds). New York, Elsevier, 1984, p 167Google Scholar
  11. 11.
    Goldenring JR, Ray GS, Coffey RJ, Meunier PC, Haley PJ, Barnes TB, Car BD: Reversible drug-induced oxyntic atrophy in rats. Gastroenterology 118:1080–1093, 2000Google Scholar
  12. 12.
    Dempsey PJ, Goldenring JR, Soroka CJ, Modlin IM, McClure RW, Lind CD, Ahlquist DA, Pittlekow MR, Lee DC, Sandgren EP, Page DL, Coffey RJ: Possible role of TGF-α in the pathogenesis of Menetrier's Disease: Supportive evidence from humans and transgenic mice. Gastroenterology 103:1950–1963, 1992Google Scholar
  13. 13.
    Goldenring JR, Ray GS, Soroka CJ, Smith J, Modlin IM, Meise KS, Coffey RJ: Overexpression of transforming growth factor-alpha alters differentiation of gastric cell lineages. Dig Dis Sci 41:773–784, 1996Google Scholar
  14. 14.
    Murayama Y, Miyagawa J, Higashiyama S, Kondo S, Yabu M, Kanayama S, Shinomura Y, Matsuzawa Y: Localization of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in human gastric mucosa. Gastroenterology 106:A622, 1994Google Scholar
  15. 15.
    Cook PW, Pittlekow MR, Keeble WW, Graves-Deal R, Coffey RJ, Shipley GD: Amphiregulin mRNA is elevated in psoriatic epidermis and gastrointestinal carcinomas. Cancer Res 52:3224–3227, 1992Google Scholar
  16. 16.
    Whitehead R: Mucosal Biopsy of the Gastrointestinal Tract, 3rd ed. Philadelphia, Saunders, 1985Google Scholar
  17. 17.
    Wong WM, Garcia SB, Poulson R, Goldenring JR, Wright NA: Aberrant spasmolytic peptide (TTF2)-expressing cell lineage (SPEM), pseudopyloric metaplasia (PPM) and the response to gastric mucosal damage. Gastroenterology 116:A525, 1999Google Scholar
  18. 18.
    Lee JR, Goldenring JR: Association of spasmolytic polypeptide expressing metaplasia (SPEM) with gastritis cystica profunda. Gastroenterology 118:A1265, 2000Google Scholar
  19. 19.
    Ray GS, Jackson MW, Goldenring JR: Foveolar hyperplasia following partial gastrectomy results from expansion of surface mucous cell compartment. Dig Dis Sci 41:2016–2024, 1996Google Scholar
  20. 20.
    Filipe MI, Munoz N, Matko I, Kato I, Pompe-Kirn V, Jutersek A, Teuchmann S, Benz M, Prijon T: Intestinal metaplasia types and the risk of gastric cancer: A cohort study in Slovenia. Int J Cancer 57:324–329, 1994Google Scholar
  21. 21.
    Rokkas T, Filipe MI, Sladen GE: Detection of an increased incidence of early gastric cancer in patient with intestinal metaplasia type III who are closely followed up. Gut 32:1110–1113, 1991Google Scholar
  22. 22.
    Tosi P, Filipe MI, Luzi P, Miracco C, Santopietro R, Lio R, Sforza V, Barbini P: Gastric intestinal metaplasia type III cases are classified as low-grade dysplasia on the basis of morphometry. J Pathol 169:73–78, 1993Google Scholar
  23. 23.
    Tatematsu M, Furihata C, Katsuyama T, Hasegawa R, Nakanowatari J, Saito D, Takahashi M, Matsushima T, Ito N: Independent induction of intestinal metaplasia and gastric cancer in rats treated with N-methyl--nitro-N-nitrosoguanidine. Cancer Res 43:1335–1341, 1983Google Scholar
  24. 24.
    Kaminishi M, Shimizu N, Shimoyama S, Yamaguchi H, Tsuji E, Aoki F, Nomura S, Yoshikawa A, Kuramoto S, Oohara T, Inada K, Tatematsu M: Denervation promotes the development of cancer-related lesions in the gastric remnant: J Clin Gastroenterol (Suppl) 25:S129–S134, 1997Google Scholar

Copyright information

© Plenum Publishing Corporation 2002

Authors and Affiliations

  • Hirokazu Yamaguchi
    • 1
    • 2
  • James R. Goldenring
    • 3
  • Michio Kaminishi
    • 1
  • Jeffrey R. Lee
    • 3
  1. 1.Department of Gastrointestinal Surgery, Graduate School of MedicineUniversity of TokyoTokyoJapan
  2. 2.Institute of Molecular Medicine and GeneticsMedical College of GeorgiaAugustaUSA
  3. 3.USA. Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, Georgia, USA

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