Skip to main content
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1998 Jun;152(6):1625–1632.

Antigen-dependent progression of mucosa-associated lymphoid tissue (MALT)-type lymphoma in the stomach. Effects of antimicrobial therapy on gastric MALT lymphoma in mice.

A Enno 1, J O'Rourke 1, S Braye 1, R Howlett 1, A Lee 1
PMCID: PMC1858462  PMID: 9626066

Abstract

In humans, low-grade B-cell mucosa-associated lymphoid tissue (MALT) lymphomas of the stomach regress when Helicobacter pylori infection is cured by antimicrobial therapy. Using an animal model of human gastric MALT lymphoma, we observed the effects of Helicobacter felis eradication and the relationship between infection and disease progression. Antimicrobial therapy was given to one-half of the BALB/c mice infected with H. felis for 20 months. Groups of antibiotic-treated and untreated mice were killed 2, 3, and 4 months after antimicrobial therapy (ie, 22, 23, and 24 months after infection). The numbers of mice with MALT decreased after H. felis eradication with no lymphoid follicles seen 4 months after treatment. MALT lymphoma was present in a total of 23% (11/48) of antibiotic-treated infected mice compared with 75% (27/36) in untreated infected mice. These lymphomas were further graded into low-, intermediate-, and high-grade lymphoma. In the untreated mice, lymphoma development was more advanced with 36% low-grade (13/36), 39% intermediate-grade (14/36), and 6% high-grade (large B-cell) lymphoma (2/36) whereas in the treated mice the incidence was 21% (10/48), 6% (3/48), and 0% (0/48), respectively. These observations suggest that antigenic stimulation by H. felis sustained growth and progression of low-grade MALT lymphoma and that primary high-grade gastric lymphomas can evolve from the transformation of these tumors. Eradication of the organism caused low-grade tumors to regress, with inhibition or slowing down of lymphoma development toward high-grade lymphoma. The H. felis mouse model of gastric MALT lymphoma presents an opportunity to address the issues arising from antimicrobial treatment of these tumors in humans.

Full text

PDF
1625

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bayerdörffer E., Neubauer A., Rudolph B., Thiede C., Lehn N., Eidt S., Stolte M. Regression of primary gastric lymphoma of mucosa-associated lymphoid tissue type after cure of Helicobacter pylori infection. MALT Lymphoma Study Group. Lancet. 1995 Jun 24;345(8965):1591–1594. doi: 10.1016/s0140-6736(95)90113-2. [DOI] [PubMed] [Google Scholar]
  2. Brooks J. J., Enterline H. T. Primary gastric lymphomas. A clinicopathologic study of 58 cases with long-term follow-up and literature review. Cancer. 1983 Feb 15;51(4):701–711. doi: 10.1002/1097-0142(19830215)51:4<701::aid-cncr2820510425>3.0.co;2-d. [DOI] [PubMed] [Google Scholar]
  3. Calvert R. J., Evans P. A., Randerson J. A., Jack A. S., Morgan G. J., Dixon M. F. The significance of B-cell clonality in gastric lymphoid infiltrates. J Pathol. 1996 Sep;180(1):26–32. doi: 10.1002/(SICI)1096-9896(199609)180:1<26::AID-PATH681>3.0.CO;2-X. [DOI] [PubMed] [Google Scholar]
  4. Chan J. K., Ng C. S., Isaacson P. G. Relationship between high-grade lymphoma and low-grade B-cell mucosa-associated lymphoid tissue lymphoma (MALToma) of the stomach. Am J Pathol. 1990 May;136(5):1153–1164. [PMC free article] [PubMed] [Google Scholar]
  5. Dick-Hegedus E., Lee A. Use of a mouse model to examine anti-Helicobacter pylori agents. Scand J Gastroenterol. 1991 Sep;26(9):909–915. doi: 10.3109/00365529108996241. [DOI] [PubMed] [Google Scholar]
  6. Du M., Diss T. C., Xu C., Peng H., Isaacson P. G., Pan L. Ongoing mutation in MALT lymphoma immunoglobulin gene suggests that antigen stimulation plays a role in the clonal expansion. Leukemia. 1996 Jul;10(7):1190–1197. [PubMed] [Google Scholar]
  7. Du M., Singh N., Husseuin A., Isaacson P. G., Pan L. Positive correlation between apoptotic and proliferative indices in gastrointestinal lymphomas of mucosa-associated lymphoid tissue (MALT). J Pathol. 1996 Apr;178(4):379–384. doi: 10.1002/(SICI)1096-9896(199604)178:4<379::AID-PATH487>3.0.CO;2-J. [DOI] [PubMed] [Google Scholar]
  8. Dunn T. B., Deringer M. K. Reticulum cell neoplasm, type B, or the "Hodgkin's-like lesion" of the mouse. J Natl Cancer Inst. 1968 Apr;40(4):771–821. [PubMed] [Google Scholar]
  9. Enno A., O'Rourke J. L., Howlett C. R., Jack A., Dixon M. F., Lee A. MALToma-like lesions in the murine gastric mucosa after long-term infection with Helicobacter felis. A mouse model of Helicobacter pylori-induced gastric lymphoma. Am J Pathol. 1995 Jul;147(1):217–222. [PMC free article] [PubMed] [Google Scholar]
  10. Genta R. M., Hamner H. W., Graham D. Y. Gastric lymphoid follicles in Helicobacter pylori infection: frequency, distribution, and response to triple therapy. Hum Pathol. 1993 Jun;24(6):577–583. doi: 10.1016/0046-8177(93)90235-9. [DOI] [PubMed] [Google Scholar]
  11. Greiner A., Knörr C., Qin Y., Sebald W., Schimpl A., Banchereau J., Müller-Hermelink H. K. Low-grade B cell lymphomas of mucosa-associated lymphoid tissue (MALT-type) require CD40-mediated signaling and Th2-type cytokines for in vitro growth and differentiation. Am J Pathol. 1997 May;150(5):1583–1593. [PMC free article] [PubMed] [Google Scholar]
  12. Hussell T., Isaacson P. G., Crabtree J. E., Dogan A., Spencer J. Immunoglobulin specificity of low grade B cell gastrointestinal lymphoma of mucosa-associated lymphoid tissue (MALT) type. Am J Pathol. 1993 Jan;142(1):285–292. [PMC free article] [PubMed] [Google Scholar]
  13. Hussell T., Isaacson P. G., Crabtree J. E., Spencer J. The response of cells from low-grade B-cell gastric lymphomas of mucosa-associated lymphoid tissue to Helicobacter pylori. Lancet. 1993 Sep 4;342(8871):571–574. doi: 10.1016/0140-6736(93)91408-e. [DOI] [PubMed] [Google Scholar]
  14. Isaacson P. G., Wotherspoon A. C., Diss T., Pan L. X. Follicular colonization in B-cell lymphoma of mucosa-associated lymphoid tissue. Am J Surg Pathol. 1991 Sep;15(9):819–828. doi: 10.1097/00000478-199109000-00001. [DOI] [PubMed] [Google Scholar]
  15. Isaacson P., Wright D. H. Malignant lymphoma of mucosa-associated lymphoid tissue. A distinctive type of B-cell lymphoma. Cancer. 1983 Oct 15;52(8):1410–1416. doi: 10.1002/1097-0142(19831015)52:8<1410::aid-cncr2820520813>3.0.co;2-3. [DOI] [PubMed] [Google Scholar]
  16. Montalban C., Manzanal A., Boixeda D., Redondo C., Bellas C. Treatment of low-grade gastric MALT lymphoma with Helicobacter pylori eradication. Lancet. 1995 Mar 25;345(8952):798–799. doi: 10.1016/s0140-6736(95)90679-7. [DOI] [PubMed] [Google Scholar]
  17. Montalbán C., Manzanal A., Castrillo J. M., Escribano L., Bellas C. Low grade gastric B-cell MALT lymphoma progressing into high grade lymphoma. Clonal identity of the two stages of the tumour, unusual bone involvement and leukemic dissemination. Histopathology. 1995 Jul;27(1):89–91. doi: 10.1111/j.1365-2559.1995.tb00299.x. [DOI] [PubMed] [Google Scholar]
  18. Myhre M. J., Isaacson P. G. Primary B-cell gastric lymphoma--a reassessment of its histogenesis. J Pathol. 1987 May;152(1):1–11. doi: 10.1002/path.1711520102. [DOI] [PubMed] [Google Scholar]
  19. Peng H., Du M., Diss T. C., Isaacson P. G., Pan L. Genetic evidence for a clonal link between low and high-grade components in gastric MALT B-cell lymphoma. Histopathology. 1997 May;30(5):425–429. doi: 10.1046/j.1365-2559.1997.5450786.x. [DOI] [PubMed] [Google Scholar]
  20. Roggero E., Zucca E., Pinotti G., Pascarella A., Capella C., Savio A., Pedrinis E., Paterlini A., Venco A., Cavalli F. Eradication of Helicobacter pylori infection in primary low-grade gastric lymphoma of mucosa-associated lymphoid tissue. Ann Intern Med. 1995 May 15;122(10):767–769. doi: 10.7326/0003-4819-122-10-199505150-00006. [DOI] [PubMed] [Google Scholar]
  21. Savio A., Franzin G., Wotherspoon A. C., Zamboni G., Negrini R., Buffoli F., Diss T. C., Pan L., Isaacson P. G. Diagnosis and posttreatment follow-up of Helicobacter pylori-positive gastric lymphoma of mucosa-associated lymphoid tissue: histology, polymerase chain reaction, or both? Blood. 1996 Feb 15;87(4):1255–1260. [PubMed] [Google Scholar]
  22. Stolte M., Eidt S. Healing gastric MALT lymphomas by eradicating H pylori? Lancet. 1993 Sep 4;342(8871):568–568. doi: 10.1016/0140-6736(93)91404-a. [DOI] [PubMed] [Google Scholar]
  23. Wotherspoon A. C., Doglioni C., Diss T. C., Pan L., Moschini A., de Boni M., Isaacson P. G. Regression of primary low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue type after eradication of Helicobacter pylori. Lancet. 1993 Sep 4;342(8871):575–577. doi: 10.1016/0140-6736(93)91409-f. [DOI] [PubMed] [Google Scholar]
  24. Wotherspoon A. C., Finn T. M., Isaacson P. G. Trisomy 3 in low-grade B-cell lymphomas of mucosa-associated lymphoid tissue. Blood. 1995 Apr 15;85(8):2000–2004. [PubMed] [Google Scholar]
  25. Wotherspoon A. C., Pan L. X., Diss T. C., Isaacson P. G. Cytogenetic study of B-cell lymphoma of mucosa-associated lymphoid tissue. Cancer Genet Cytogenet. 1992 Jan;58(1):35–38. doi: 10.1016/0165-4608(92)90130-z. [DOI] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES