Helicobacter pylori-gastrin link in MALT lymphoma.

BACKGROUND: There is accumulating evidence for the role of Helicobacter pylori in the development of gastric cancer as well as of lymphomas that arise in mucosa-associated lymphoid tissue (MALT). We reported recently that gastric cancer patients show high prevalence of cagA-positive H. pylori and express gastrin and gastrin receptors enabling them to stimulate tumour growth in autocrine fashion. AIMS: Since the H. pylori infection is considered to be more strongly associated with MALT lymphoma than with gastric cancer, we decided to determine the gastrin and its receptors' mRNA expression and gastrin content in this tumour as well as the release of this hormone both into plasma and gastric lumen. Twenty MALT lymphoma patients were compared with 100 age- and gender-matched controls with similar dyspeptic symptoms. RESULTS: The overall H. pylori seropositivity in MALT lymphoma was about 90% and CagA positivity was 70%, compared to 56% and 33%, respectively, in controls. The serum gastrin in MALT lymphoma was about sixfold higher than in controls while gastric luminal gastrin in these patients was over 70 times higher than in controls. Gastrin content in tumour was about 10-fold higher than in antral mucosa. Gastrin and gastrin-receptor (CCKB-receptor) mRNA were detected by reverse transcriptase-polymerase chain reaction in cancer tissue whilst in the fundic and antral mucosa, only enhanced expression of CCKB-receptor mRNA and gastrin mRNA was detected, respectively. Histamine stimulation in MALT lymphoma induced acid secretion that was only about 30% of control value due to atrophic gastritis. This study confirms an important role of CagA-positive H. pylori in the pathogenesis of MALT lymphoma and shows that this lymphoma is capable of synthesizing and releasing potent growth promoting gastrin, possibly due to the action on G-cells of H. pylori-originated Nalpha-methyl histamine and cytokines (tumour necrosis factor alpha and interleukin-8). CONCLUSIONS: Gastric MALT lymphoma is closely linked to CagA-positive H. pylori infection. Gastrin and its receptors may be implicated in the pathogenesis of gastric lymphoma.