TRAF1 expression and c-Rel activation are useful adjuncts in distinguishing classical Hodgkin lymphoma from a subset of morphologically or immunophenotypically similar lymphomas.
We demonstrate that the expression of TRAF1 and activated c-Rel, two proteins that function in signaling events downstream of activated CD30 in Reed-Sternberg cells, reliably distinguish classical Hodgkin lymphoma from anaplastic large cell lymphoma, nodular lymphocyte predominant Hodgkin lymphoma, and nonmediastinal diffuse large B-cell lymphoma. By immunohistochemistry, we found strong TRAF1 staining in 21 of 25 cases of classical Hodgkin lymphoma. In contrast, strong TRAF1 staining was present in only 1 of 17 cases of anaplastic large cell lymphoma, 0 of 15 cases of lymphocyte predominant Hodgkin lymphoma, and 2 of 36 cases of nonmediastinal diffuse large B-cell lymphoma. Nuclear staining for c-Rel, a pattern consistent with NFkappaB activation, was observed in the Reed-Sternberg cells in 23 of 25 cases of classical Hodgkin lymphoma but only in 1 of 15 cases of anaplastic large cell lymphoma and 3 of 15 cases of nodular lymphocyte predominant Hodgkin lymphoma. A heterogeneous pattern of subcellular c-Rel localization was found in nonmediastinal diffuse large B-cell lymphoma. Taken together, the combination of strong cytoplasmic TRAF1 expression and nuclear c-Rel was present in 80% of cases of classical Hodgkin lymphoma (n = 25) but in only 3% of cases of the other malignant lymphomas tested (n = 62). Thus, the differential expression patterns of downstream components in the CD30 signaling pathway may prove a useful adjunct in distinguishing cases of classical Hodgkin lymphoma from other malignant lymphomas in routine clinical practice.
Rodig
Scott J
SJ
Department of Pathology, Brigham & Women's Hospital, Dana Farber Cancer Institute, Boston, MA 02115, USA.
Savage
Kerry J
KJ
Nguyen
Vuong
V
Pinkus
Geraldine S
GS
Shipp
Margaret A
MA
Aster
Jon C
JC
Kutok
Jeffery L
JL
D014408:Biomarkers, Tumor / Q000032:analysis; D003937:Diagnosis, Differential; D004789:Enzyme Activation / Q000502:physiology; D006689:Hodgkin Disease / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D017730:Ki-1 Antigen / Q000378:metabolism; D008223:Lymphoma / Q000378:metabolism / Q000473:pathology*; D020569:Proto-Oncogene Proteins c-rel / Q000378:metabolism*; D016539:Reed-Sternberg Cells / Q000378:metabolism; D047990:TNF Receptor-Associated Factor 1 / Q000096:biosynthesis*
D014408:Biomarkers, Tumor; D017730:Ki-1 Antigen; D020569:Proto-Oncogene Proteins c-rel; D047990:TNF Receptor-Associated Factor 1