Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is a distinct low-grade lymphoma that often regresses upon Helicobacter pylori eradication. It was reported that the chemokine receptor CXCR3 is expressed not only on activated T cells, but also on MALT lymphoma cells, and that CXCR3-positive B lymphocytes migrate or home to the MALT of MALT lymphoma. In the present study, we aimed to elucidate the correlation between CXCR3 expression and the clinicopathological features of gastric MALT lymphoma, and to determine whether CXCR3 expression was predictive of responsiveness to H. pylori eradication. Sixty-seven patients with gastric MALT lymphoma in a single-center study were treated with H. pylori eradication therapy. We evaluated the correlation of CXCR3 expression with response to H. pylori eradication therapy by logistic regression stratified according to potential confounders. Immunohistochemical analysis revealed that 28 of 67 cases (42%) were positive for CXCR3 expression. CXCR3 expression was significantly more prevalent in those without H. pylori infection, advanced-stage disease, and in those with API2-MALT1 fusion. In overall analysis, those with CXCR3 expression showed a significantly increased risk of non-responsiveness to H. pylori eradication therapy (odds ratio = 28.6; 95% confidence interval 5.70-143.4) compared to those without CXCR3 expression. This higher risk was observed consistently regardless of sex, API2-MALT1 fusion, H. pylori infection, or clinical stage. We showed that CXCR3 expression was an independent predictive factor for non-responsiveness to H. pylori eradication therapy in patients with gastric MALT lymphoma.

Clinical features and prognosis of gastric MALT lymphoma with special reference to responsiveness to H. pylori eradication and API2-MALT1 status.Am J Gastroenterol. 2008 Jan;103(1):62-70. Epub 2007 Sep 25.

BACKGROUND AND AIM: Clinicopathologic characteristics and prognosis of Helicobacter pylori eradication-resistant gastric MALT lymphoma have not been well clarified. We analyzed a consecutive series of gastric MALT lymphomas at our institution regarding treatment, clinical course, and prognosis, with special reference to responsiveness to H. pylori eradication and presence of API2-MALT1. METHODS: Subjects were 92 consecutive patients with gastric MALT lymphoma. Seventy were H. pylori positive, and 87 received H. pylori eradication therapy. The remaining five cases were API2-MALT1 positive and did not receive eradication treatment. Second-line treatments were radiation therapy, total gastrectomy, and chemotherapy (rituximab, rituximab plus CHOP, or rituximab plus 2-chlorodeoxyadenosine). RESULTS: Gastric MALT lymphoma was classified into three groups, except one case with API2-MALT1 who responded to H. pylori eradication therapy: responders without API2-MALT1 (group A, N = 56, 65%), nonresponders without API2-MALT1 (group B, N = 16, 19%), and nonresponders with API2-MALT1 (group C, N = 14, 16%). Most cases in group A attained complete remission (CR) in 2 or 3 months and CR persisted for an average of 51.1 months (3-134 months). Recurrence was only seen in one case. In groups B and C, radiation therapy, chemotherapy, and total gastrectomy resulted in CR in 13, 5, and 2 cases, respectively. In 5 group B patients and 6 group C patients who did not undergo second-line therapy, disease did not progress for an average of 10.4 and 40.1 months, respectively. In 1 group C case who did not receive second-line treatment, lymphoma metastasized to the lung 12 yr after eradication. All group B patients and all but 2 group C patients remain alive; one of these deaths was from gastric carcinoma developing 7 yr after eradication. CONCLUSION: Gastric MALT lymphoma responding to H. pylori eradication demonstrated good prognosis, and for nonresponsive cases, second-line treatments resulted in CR. However, careful observation for development of gastric carcinoma and disease progression is essential during follow-up of API2-MALT1-positive MALT lymphoma when patients decline second-line treatment.