Frequent expression of the tumor necrosis factor receptor-associated factor 1 in latent membrane protein 1-positive posttransplant lymphoproliferative disease and HIV-associated lymphomas

Paul G. Murray, Lode J. Swinnen, Joanne R. Flavell, Margaret V. Ragni, Karl R.N. Baumforth, Siobhan M. Toomey, Alexandra H. Filipovich, Derek Lowe, Carrie S. Schnell, Jewel Johl, Margaret Gulley, Lawrence S. Young, Richard F. Ambinder

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)963-969
Number of pages7
JournalHuman pathology
Volume32
Issue number9
DOIs
StatePublished - Jan 1 2001

Keywords

  • Epstein-Barr virus
  • Latent membrane protein 1
  • Posttransplant lymphoma
  • Tumor necrosis factor receptor-associated factor 1

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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  • Cite this

    Murray, P. G., Swinnen, L. J., Flavell, J. R., Ragni, M. V., Baumforth, K. R. N., Toomey, S. M., Filipovich, A. H., Lowe, D., Schnell, C. S., Johl, J., Gulley, M., Young, L. S., & Ambinder, R. F. (2001). Frequent expression of the tumor necrosis factor receptor-associated factor 1 in latent membrane protein 1-positive posttransplant lymphoproliferative disease and HIV-associated lymphomas. Human pathology, 32(9), 963-969. https://doi.org/10.1053/hupa.2001.27114