Expression of TNF-receptor associated factor 2 correlates with poor progression-free survival time in ABC-like primary nodal diffuse large B-cell lymphomas

Histopathology. 2008 Apr;52(5):578-84. doi: 10.1111/j.1365-2559.2008.02970.x. Epub 2008 Feb 23.

Abstract

Aims: Tumour necrosis factor (TNF)-receptor associated factor 2 (TRAF2) is an adaptor molecule involved in nuclear factor (NF)-kappaB activation, which is characteristic of in vitro activated B-cell (ABC)-like diffuse large B-cell lymphomas (DLBCL) and may result in expression of anti-apoptotic genes and poor response to chemotherapy. TRAF2 also has direct anti-apoptotic properties via interference with the apoptosis signalling cascade. The aim was to determine whether TRAF2 is preferentially expressed in ABC-like DLBCL, and whether expression correlates with clinical outcome.

Methods and results: TRAF2 was expressed in nine of 20 tested ABC-like DLBCLs and in only one of 13 tested germinal centre B-lymphocyte (GCB)-like DLBCLs. High TRAF2 expression was correlated with high International Prognostic Index at time of presentation, high chance of relapse and short progression-free survival time in 44 tested DLBCLs. Furthermore, when analysis was restricted to ABC-like DLBCL only, TRAF2 expression was significantly associated with poor progression-free survival time.

Conclusions: TRAF2 might be involved in activation of NF-kappaB in a subset of ABC-like DLBCL, and its expression is associated with a particularly poor outcome in primary nodal DLBCL patients. Because of its possible effect on to chemotherapy resistance, resistance, TRAF2 might be an attractive candidate as a molecular target for TRAF2+ DLBCL.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • B-Lymphocytes / metabolism*
  • B-Lymphocytes / pathology
  • Biomarkers, Tumor / metabolism
  • Combined Modality Therapy
  • Cyclophosphamide / therapeutic use
  • Disease-Free Survival
  • Doxorubicin / therapeutic use
  • Female
  • Fluorescent Antibody Technique, Direct
  • Germinal Center / pathology
  • Humans
  • Immunoenzyme Techniques
  • Lymphoma, Large B-Cell, Diffuse / diagnosis
  • Lymphoma, Large B-Cell, Diffuse / metabolism*
  • Lymphoma, Large B-Cell, Diffuse / mortality
  • Male
  • Middle Aged
  • Prednisone / therapeutic use
  • Radiotherapy, Adjuvant
  • Survival Rate
  • TNF Receptor-Associated Factor 2 / metabolism*
  • Vincristine / therapeutic use

Substances

  • Biomarkers, Tumor
  • TNF Receptor-Associated Factor 2
  • Vincristine
  • Doxorubicin
  • Cyclophosphamide
  • Prednisone

Supplementary concepts

  • CHOP protocol