Classic
Hodgkin lymphoma (cHL) is characterized by numerical gains of the short arm of chromosome 2. The high frequency of 2p overrepresentation including REL, particularly in the nodular
sclerosis subtype suggests that constitutive activation of
nuclear factor kappaB/REL is a hallmark of Reed-Sternberg (RS) cells. The aim of this study was to investigate
c-Rel protein expression patterns in cHL and nodular lymphocyte predominant
Hodgkin lymphoma (NLPHL) cases by immunohistochemical analysis. A total of 79 cases of HL were analyzed, which included 59 cases of cHL (49 nodular
sclerosis; 8 mixed cellularity; 2 lymphocyte-rich) and 20 cases of NLPHL. Positive staining was defined in this study as a reaction seen in the nuclei or nuclei and cytoplasm of RS or lymphocytic and histiocytic (L&H) cells in cHL and NLPHL cases, respectively. The percent positivity of c-REL staining of RS cells in cHL was seen in 51 of 59 cases (86.4%). No significant difference in c-REL expression was seen between nodular
sclerosis (42 of 49, 85.7%) and mixed cellularity subtypes (7 of 8 cases, 87.5%; P = 1). In comparison, positive
c-REL protein expression in L&H cells was seen in 5 of 20 NLPHL cases (25.0%). Therefore, significantly higher positivity of RS cells in cHL was seen compared with positivity of L&H cells in NLPHL; 86.4% vs. 25.0%; P = 0). Expression of Epstein-Barr virus latent
membrane protein was seen in 6 of 30 cases (19.0%; 25 cHL, 5 NLPHL) and
EBER1 in 5 of 27 cases (18.5%; 24 cHL, 3 NLPHL). The presence of Epstein-Barr virus did not correlate with
c-REL protein expression (P = 1). Our results demonstrate that there is differential
c-REL protein expression in cHL in comparison with NLPHL and suggest that c-REL may play a role in the pathogenesis of classic
Hodgkin lymphoma.