Frequent expression of the tumor necrosis factor receptor-associated factor 1 in latent membrane protein 1-positive posttransplant lymphoproliferative disease and HIV-associated lymphomas.
The tumor necrosis factor receptor-associated factor 1 (TRAF1) participates in the signal transduction of various members of the tumor necrosis factor receptor (TNFR) family, including TNFR2, CD40, CD30, and the Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1). In vitro, TRAF1 is induced by LMP1, and previous studies have suggested that expression of TRAF1 is higher in EBV-associated tumors than in their EBV-negative counterparts. To determine whether this was the case in posttransplant lymphoproliferative disease (PTLD) and related disorders, we used immunohistochemistry to analyze expression of TRAF1 in a total of 42 such lesions arising in a variety of immunosuppressive states. The specimens consisted of 22 PTLD lesions, 18 acquired immunodeficiency syndrome-associated lymphomas, including 6 primary central nervous system lymphomas, and 2 cases of Hodgkin disease. The presence of latent EBV infection was determined by EBER in situ hybridization, and expression of EBV-LMP1 was detected by immunohistochemistry. Latent EBV infection, as determined by a positive EBER signal, was detected in 36 of 42 tumors. Of the EBER-positive specimens, 30 of 36 also expressed LMP1. Twenty-four of 30 LMP1-positive tumors, including both Hodgkin disease specimens, expressed TRAF1, compared with only 3 of 12 LMP1-negative tumors. This difference was statistically significant (P <.005). These results show frequent expression of TRAF1 at the protein level in LMP1-positive PTLD and related disorders and suggest an important role for LMP1-mediated TRAF1 signaling in the pathogenesis of EBV-positive tumors arising in immunosuppressive states.
Murray
P G
PG
Division of Cancer Studies, University of Birmingham, Edgbaston, Birmingham, England.
Swinnen
L J
LJ
Flavell
J R
JR
Ragni
M V
MV
Baumforth
K R
KR
Toomey
S M
SM
Filipovich
A H
AH
Lowe
D
D
Schnell
C S
CS
Johl
J
J
Gulley
M
M
Young
L S
LS
Ambinder
R F
RF
D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000378:metabolism / Q000473:pathology; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D016483:Lymphoma, AIDS-Related / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D008232:Lymphoproliferative Disorders / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D016377:Organ Transplantation; D011183:Postoperative Complications; D011506:Proteins / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000032:analysis; D012269:Ribosomal Proteins; D047990:TNF Receptor-Associated Factor 1; D014763:Viral Matrix Proteins / Q000378:metabolism*
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D011506:Proteins; D016601:RNA-Binding Proteins; D012269:Ribosomal Proteins; D047990:TNF Receptor-Associated Factor 1; D014763:Viral Matrix Proteins; C067169:RPL22 protein, human