Histological and immunological parameters to predict treatment outcome ofHelicobacter pylori eradication in low-grade gastric MALT lymphoma

Abstract

Helicobacter pylori eradication is generally accepted as the first choice of treatment for stage IE low-grade gastric MALT lymphoma (mucosa-associated lymphoid tissue-type lymphoma). Treatment failure may be attributed to the extent of the disease and to progression into an antigen-independent phase. This study assessed the value of morphological grading and the expression of the co-stimulatory markers CD40, CD80 and CD86 and their ligands to predict clinical outcome in 23 consecutive low-grade MALT lymphoma patients treated with H. pylori eradication. Complete regression was achieved in 13/23 patients (56%), partial regression in two (9%), and no response in eight (35%). Histological grading was highly predictive of clinical response, especially in stage IE(1) patients, with complete remissions in 10/12 tumours with purely low-grade (type A) morphology and 1/8 tumours with increased numbers of blasts (type B) (p=0.0046) and was related to the expression of costimulatory markers (p=0.0061). Moreover, CD86 as a single marker proved to be of predictive value for treatment outcome (p=0.0086). These results suggest that morphological grading and immunological criteria can be defined to recognize the transition into the antigen-independent phase of gastric MALT-NHL. In addition to clinical stage, these critera may in future serve as a practical pathological guide to the choice of therapy.

Expression of CD86 and increased infiltration of NK cells are associated withHelicobacter pylori-dependent state of early stage high-grade gastric MALT lymphoma

“…Compared with CD86, CD80 delivered a down-regulator signal for B-cell response [26] . In a recent study of low-grade gastric MALT lymphomas, the expression of CD86 was significantly associated with H pylori-dependence, while CD80 and CD40 and their ligands were not [27] . These results are in line with our observation that the co-stimulatory molecule CD86 is present in high-grade gastric MALT lymphomas, and is also significantly associated with H pylori-dependence.…”

Differential expression of NF-κB target genes in MALT lymphoma with and without chromosome translocation: insights into molecular mechanism

“…In line with our finding, a previous study showed significantly higher CD86 expression in gastric MALT lymphomas that responded to H. pylori eradication than those resisted to the therapy (66% vs 10%). 39 Although the chromosome translocation status in these cases is not available, it is most likely that the cases responded to H. pylori were translocation-negative.…”

Molecular pathogenesis of MALT lymphoma: two signaling pathways underlying the antiapoptotic effect of API2-MALT1 fusion protein

“…85,86 In addition, expression of costimulatory molecules, such as CD80 and CD86, was demonstrated in gastric MALT lymphoma cells, and it was found that the presence of the costimulatory molecule CD86 on the cells may promote T-cellmediated neoplastic B-cell growth. 87 It has been proposed that chronic antigenic stimulation by H. pylori triggers T-cell-mediated B-cell growth via activation of CD40 and NF-kB pathway early in the development of gastric MALT lymphoma. In this connection, Ho et al 88 recently examined the effect of stably expressed MALT1 and API2-MALT1 in human B-cell lines on the NF-kB signaling pathway and elegantly demonstrated that cytoprotection mediated by NF-kB, once activated in a CD40-mediated immune response, is maintained and enhanced through deregulation of MALT1 or formation of API2-MALT1 fusion.…”