Background: Recent data suggest that conventional chemotherapy has various degree of effectiveness in the treatment of H. pylori-independent gastric mucosa-associated lymphoid tissue (MALT) lymphoma. It has been shown that the chimeric protein of t(11;18)(q21;q21) can lead to constitutive NF-κB activity and thereby mediate cell survival and anti-apoptotic signals. Recent studies also demonstrate that FOXP1 expression is associated with the risk of lymphomagenesis and high-grade transformation of MALT lymphoma. The present study sought to clarify the correlation of translocation t(11;18)(q21;q21), nuclear NF-κB expression, and FOXP1 expression with chemoresistance of patients with H. pylori-independent gastric MALT lymphoma. Materials and methods We reviewed the pathologic materials of H. pylori-independent gastric MALT lymphoma patients (stage I-IIE patients who fail to H. pylori eradication therapy and stage IIIE-IV patients) and who had been treated by systemic chemotherapy (oral alkylating agents or combined regimens) in our institutions between January 1, 1995 through December 31, 2002. The presence of t(11;18)(q21;q21) was identified by a multiplex RT-PCR of the API2-MALT1 chimeric transcript. The expression of NF-κB and FOXP1 in pre-treatment paraffin-embedded lymphoma tissues was determined by immunohistochemistry. Tumors were considered chemo-sensitive if complete remission (CR) was documented after systemic chemotherapy. Results: Ten patients with (responders) and 15 patients without (nonresponders) chemotherapy responsiveness were identified. At a median follow-up of 100 months (range, 29-143 months), the 5-year overall survival rate was 100 % for responders and 83 % for nonresponders (P = .241). As a single variable, the frequency of API2-MALT1 fusion transcript (67% vs. 20%, P = .041), nuclear expression of NF-κB (87% vs. 40%, P = .028), and aberrant expression of FOXP1 (80% vs. 30%, P = .034) was significantly higher in nonresponders than in responders. Based on these findings, we conducted a three-biomarkers chemoresponsive scoring system that predict CR rate of 100%, 60%, and 20%, (P = .007), respectively, for these patients with none, one, or more than one biomarkers, respectively. Conclusion: Our study indicate that the presence of more than one t(11;18), nuclear NF-κB expression, and FOXP1 expression in tumors is highly predictive of chemotherapy resistance in H. pylori-independent gastric MALT lymphoma patients. Additional investigation of the molecular mechanisms and biologic significance of these biomarkers in this group of tumors is needed.
99th AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA