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.