Relation of Helicobacter heilmannii infection to gastric MALT lymphoma formation in human and mouse

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1. Mouse Modelthe MALT lymphoma tissue was shown to have rich microvascular network consisting of the immature capillaries and venules, revealed by electron microscopy. By the immunohistochemical analysis, very much enhanced VEGF-A immunoreactivity was observed in the whole MALT lymphoma tissue, while VEGF-C immunoreactivity was observed only in the marginal area of the lymphoma. Both Flt-1 and Flk-1 were expressed in the lymphoma tissues. Flk-1 were mainly expressed in the immature endothelial cells, while Flt-1 were observed in the accumulated lymphocytes. The treatment with VEGF receptor monoclonal antibody significantly decreased the size of the protrusive lesion. In conclusion, VEGF-mediated mechanism was shown to play an important role in the expansion of the MALT lymphoma tissue induced by Hh infection in C57BL/6 mice.2. Human Casesout of 12 MALT lymphoma cases 4 cases were positive to Hp, 5 positive to HHLO and among them 4 cases were doubly positive to HHLO and Hp. By Fisher's exact test, HHLO infection as well as Hp and HHLO co-nfection was significantly related to the MALT lymphoma. By the analysis of urease gene, 4 cases were found to belong to Hs 'infection among 9 HHLO positive patients, while other cases were not identified to either Hh, Hs or Hf. By the in situ hybridization method, the Hh was recognized near the surface epithelial cells and fundic glandular cells including parietal cells, which coincided well with our previous infection study using C57BL/6 mice. On the other hand, 129 cases were positive to Hp and only 4 cases were positive to HHLO out of 221 non-MALT lymphoma cases. In conclusion, HHLO and Hp coinfection has shown to be closely related to MALT lymphoma in Japanese cases.