title: A novel A20 (TNFAIP3) antibody (Ber-A20) can be used to detect unmutated A20 by immunohistology.
abstract: OBJECTIVE
  A20 (TNFAIP3) is a nuclear factor-κB (NF-κB)-inducible component of tumour necrosis factor and Toll-like receptor intracellular signal transduction. It negatively regulates NF-κB, and has been identified as a tumour suppressor. Several studies have described A20 inactivation by deletion of the A20 locus at 6q23, inactivating mutations, and/or methylation of the A20 promoter in various lymphoma entities.
  
  
  RESULTS
  We generated a monoclonal antibody against the C-terminus of A20 (Ber-A20) and investigated full-length A20 expression of normal lymphoid tissue and lymphomas for the first time. We identified loss of A20 expression in tumour cells of 24% of classical Hodgkin lymphoma, 27% of diffuse large B-cell lymphoma, 20% of chronic lymphocytic leukaemia, 19% of follicular lymphoma, 13% of mantle cell lymphoma and 8% of primary mediastinal B-cell lymphoma cases by immunohistology. Loss of A20 expression rarely occurred in T-cell non-Hodgkin lymphoma.
  
  
  CONCLUSIONS
  Our data are in agreement with cytogenetic and molecular analyses. Among 21 cases of ocular adnexal marginal zone lymphomas with known A20 mutation status, we detected complete absence of A20 expression, whereas cases with wild-type A20 were weakly A20-positive. We demonstrate that A20 loss can be detected by immunohistology with a sensitivity similar to that of complex molecular and genetic methods.
authors.affiliation: Institute of Pathology (CBF), Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Hirsch
authors.forename: Maria
authors.initials: M
authors.lastname: Grünbaum
authors.forename: Florian
authors.initials: F
authors.lastname: Wagner
authors.forename: Yingwen
authors.initials: Y
authors.lastname: Bi
authors.forename: Lothar
authors.initials: L
authors.lastname: Lucka
authors.forename: Ming-Qing
authors.initials: MQ
authors.lastname: Du
authors.forename: Harald
authors.initials: H
authors.lastname: Stein
authors.forename: Horst
authors.initials: H
authors.lastname: Dürkop
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000276:immunology / Q000378:metabolism*; D005134:Eye Neoplasms / Q000378:metabolism; D006689:Hodgkin Disease / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology / Q000378:metabolism*; D008228:Lymphoma, Non-Hodgkin / Q000378:metabolism; D009154:Mutation; D009687:Nuclear Proteins / Q000276:immunology / Q000378:metabolism*; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3
chemical_list: D000911:Antibodies, Monoclonal; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3