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


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.
van Galen
J C
JC
Departments of Pathology and Haematology, VU Medical Centre, Amsterdam, The Netherlands.
Muris
J J F
JJ
Giroth
C P E
CP
Vos
W
W
Ossenkoppele
G J
GJ
Meijer
C J L M
CJ
Oudejans
J J
JJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000627:therapeutic use; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D019085:Fluorescent Antibody Technique, Direct; D018858:Germinal Center / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000627:therapeutic use; D018714:Radiotherapy, Adjuvant; D015996:Survival Rate; D047992:TNF Receptor-Associated Factor 2 / Q000378:metabolism*; D014750:Vincristine / Q000627:therapeutic use
D014408:Biomarkers, Tumor; D047992:TNF Receptor-Associated Factor 2; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone