Expression of c-FLIP is primarily detected in diffuse large B-cell lymphoma and Hodgkin's lymphoma and correlates with lack of caspase 8 activation.
OBJECTIVE
Inhibition of apoptosis is important in the pathogenesis of lymphomas. c-FLIP, a regulator of caspase 8-mediated apoptosis, plays an important role in protecting normal B and T cells from apoptosis and possibly also in lymphomas. Because of contradictory reports about immunohistochemical detection of c-FLIP expression, the aim was to test the specificity of four antibodies in c-FLIP-transfected cells and subsequently to investigate expression of c-FLIP in different types of lymphoma.


RESULTS
Two of four antibodies were specific. In primary lymphomas c-FLIP expression was restricted to Hodgkin's lymphomas (> 90%) and diffuse large B-cell lymphomas (44%). Burkitt lymphomas and indolent B-cell lymphomas were negative in all cases. No expression was detected in primary T-cell lymphomas, although expression was observed in one relapsed ALK+ anaplastic large cell lymphoma. Expression of c-FLIP was inversely correlated with caspase 8 activation.


CONCLUSIONS
c-FLIP is important in escape of B cells from apoptosis during normal follicle centre cell reaction and may thus be an important early event in the development of B-cell-derived lymphomas. Moreover, non-specific staining of frequently used antibodies might explain discrepancies in different reports of c-FLIP expression.
Department of Pathology, VUMC, Amsterdam, The Netherlands.
I S
IS
van Houdt
J J
JJ
Muris
A T
AT
Hesselink
D
D
Kramer
S A G M
SA
Cillessen
L M
LM
Moesbergen
W
W
Vos
E
E
Hooijberg
C J L M
CJ
Meijer
J A
JA
Kummer
J J
JJ
Oudejans
D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000096:biosynthesis*; D053181:Caspase 8 / Q000378:metabolism*; D004789:Enzyme Activation / Q000502:physiology; D006689:Hodgkin Disease / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D053181:Caspase 8