ANTIGEN-DEPENDENT PROGRESSION OF MUCOSA-ASSOCIATED LYMPHOID-TISSUE (MALT)-TYPE LYMPHOMA IN THE STOMACH - EFFECTS OF ANTIMICROBIAL THERAPY ON GASTRIC MALT LYMPHOMA IN MICE

In humans, low-grade B-cell mucosa-associated lymphoid tissue (MALT) l ymphomas 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 eradicat ion and the relationship between infection and disease progression. An timicrobial therapy was given to one-half of the BALB/c mice infected with H. felis for 20 months. Groups of antibiotic-treated and untreate d 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 l ow-, intermediate-, and high-grade lymphoma. In the untreated mice, ly mphoma development was more advanced with 36% low-grade (13/36), 39% i ntermediate-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 ant igenic 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 or ganism 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 addres s the issues arising from antimicrobial treatment of these tumors in h umans.