Expression of c-FLIP in classic and nodular lymphocyte-predominant Hodgkin lymphoma.
Different molecular pathways are believed to be involved in the pathogenesis of classic Hodgkin lymphoma as opposed to non-Hodgkin lymphoma. Antiapoptotic mechanisms have been proposed for classic Hodgkin lymphoma, including expression of the cellular Fas-associated death domain-like interleukin-1beta-converting enzyme inhibitory protein (c-FLIP), which plays a critical role in resistance to CD95/Fas-mediated apoptosis. In this study, we compare the expression of c-FLIP in the neoplastic cells of classic Hodgkin lymphoma and nodular lymphocyte-predominant Hodgkin lymphoma cases. Sixteen cases of classic Hodgkin lymphoma and 19 cases of nodular lymphocyte-predominant Hodgkin lymphoma were reviewed. Of 16 classic Hodgkin lymphoma cases, 13 cases (81%) were c-FLIP-positive, compared with 6 of 19 (32%) nodular lymphocyte-predominant Hodgkin lymphoma cases. Strong cytoplasmic staining was seen in 7 of 13 c-FLIP-positive classic Hodgkin lymphoma cases, in contrast with only 2 of 6 c-FLIP-positive nodular lymphocyte-predominant Hodgkin lymphoma cases. The 2 cases of nodular lymphocyte-predominant Hodgkin lymphoma with strong c-FLIP expression were associated with transformation to large B-cell lymphoma. An additional 15 cases of diffuse large B-cell lymphoma were studied for c-FLIP expression. All but 1 were c-FLIP-positive. In conclusion, we detected c-FLIP in a significantly lower proportion of nodular lymphocyte-predominant Hodgkin lymphoma cases compared with classic Hodgkin lymphoma cases. Therefore, c-FLIP expression may not be the major mechanism of pathogenesis in nodular lymphocyte-predominant Hodgkin lymphoma. However, strong c-FLIP expression in nodular lymphocyte-predominant Hodgkin lymphoma was associated with transformation to large B-cell lymphoma in 2 cases. c-FLIP expression is not limited to Hodgkin lymphoma, because the majority of diffuse large B-cell lymphoma cases tested were strongly c-FLIP-positive.
Uherova
Patricia
P
Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee 37204, USA.
Olson
Sandy
S
Thompson
Mary Ann
MA
Juskevicius
Ridas
R
Hamilton
Katherine S
KS
D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D000951:Antigens, Neoplasm / Q000032:analysis* / Q000235:genetics; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics; D061945:Caspase Inhibitors; D002471:Cell Transformation, Neoplastic / Q000737:chemistry / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006689:Hodgkin Disease / Q000145:classification / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D008198:Lymph Nodes / Q000473:pathology*; D016393:Lymphoma, B-Cell / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000473:pathology; D008297:Male; D008875:Middle Aged
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D002352:Carrier Proteins; D061945:Caspase Inhibitors; D047908:Intracellular Signaling Peptides and Proteins