title: E2A-positive gastric MALT lymphoma has weaker plasmacytoid infiltrates and stronger expression of the memory B-cell-associated miR-223: possible correlation with stage and treatment response.
abstract: Extranodal marginal-zone lymphoma of mucosa-associated lymphoid tissue of the stomach (gastric MALT lymphoma) is derived from memory B cells of the marginal zone. Normal memory B cells do not express markers of germinal-center B cells, such as E2A (immunoglobulin enhancer-binding factor E12/E47), B-cell chronic lymphocytic leukemia/lymphoma 6 (BCL6), or activation-induced cytidine deaminase (AID). E2A is a transcription factor that induces somatic hypermutations and blocks plasma cell differentiation. In 50 stage-I(E)/II(E1) gastric MALT lymphomas, we confirmed that all cases were BCL6(-)/AID(-), but a subset (50%, 25/50) was E2A(+). As E2A(-) and E2A(+) gastric MALT lymphomas had similar numbers of somatic hypermutations without intraclonal variations, which implied an origin from memory B cells, the expression of E2A was best regarded as a marker of aberrant follicular differentiation. Although the status of somatic hypermutation was not affected by E2A, E2A(+) gastric MALT lymphoma showed less plasmacytoid infiltrates and higher expressions of miRNA-223, a microRNA associated with memory B cells. Clinically, E2A(+) gastric MALT lymphomas were more likely to spread to perigastric lymph nodes and were less responsive to Helicobacter eradication therapy than were E2A(-) gastric MALT lymphomas. Taken together, aberrant E2A expression is a diagnostic feature of a subtype of gastric MALT lymphoma with weaker plasmacytoid infiltrates and stronger miR-223 expression. A prospective study would be necessary to verify the association between E2A expression and a poor response to Helicobacter eradication therapy.
authors.affiliation: Department of Pathology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan, ROC.
authors.forename: Ting-Yun
authors.initials: TY
authors.lastname: Liu
authors.forename: Shee-Uan
authors.initials: SU
authors.lastname: Chen
authors.forename: Sung-Hsin
authors.initials: SH
authors.lastname: Kuo
authors.forename: Ann-Lii
authors.initials: AL
authors.lastname: Cheng
authors.forename: Chung-Wu
authors.initials: CW
authors.lastname: Lin
mesh_terms: D001402:B-Lymphocytes / Q000737:chemistry* / Q000276:immunology / Q000473:pathology; D051792:Basic Helix-Loop-Helix Proteins / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D002454:Cell Differentiation; D016000:Cluster Analysis; D003564:Cytidine Deaminase / Q000032:analysis; D004268:DNA-Binding Proteins / Q000032:analysis; D015972:Gene Expression Regulation, Neoplastic; D050438:Genes, Immunoglobulin Heavy Chain; D016481:Helicobacter Infections / Q000188:drug therapy / Q000382:microbiology; D016480:Helicobacter pylori / Q000472:pathogenicity; D006801:Humans; D007150:Immunohistochemistry; D007156:Immunologic Memory; D008198:Lymph Nodes / Q000737:chemistry* / Q000276:immunology / Q000473:pathology; D018442:Lymphoma, B-Cell, Marginal Zone / Q000737:chemistry* / Q000235:genetics / Q000276:immunology / Q000382:microbiology / Q000473:pathology / Q000628:therapy; D035683:MicroRNAs / Q000032:analysis*; D009154:Mutation; D009367:Neoplasm Staging; D010950:Plasma Cells / Q000737:chemistry* / Q000276:immunology / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000032:analysis; D051560:Proto-Oncogene Proteins c-bcl-6; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000276:immunology / Q000382:microbiology / Q000473:pathology / Q000628:therapy; D013624:Taiwan; D016896:Treatment Outcome; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor; D003564:Cytidine Deaminase; D004268:DNA-Binding Proteins; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D000098830:AICDA (Activation-Induced Cytidine Deaminase); C084103:BCL6 protein, human; C525067:MIR223, human; C407909:TCF3 protein, human; C090851:TCL1A protein, human