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

• Published in: Histopathology 2007-12, Vol.51 (6), p.778-784
• Main Authors: Van Houdt, I S, Muris, J J, Hesselink, A T, Kramer, D, Cillessen, S A G M, Moesbergen, L M, Vos, W, Hooijberg, E, Meijer, C J L M, Kummer, J A, Oudejans, J J
• Format: Article
• Language: English
• Subjects: antibodies; Antibodies, Monoclonal; Antibody Specificity; apoptosis; B-cell lymphomas; Biological and medical sciences; CASP8 and FADD-Like Apoptosis Regulating Protein - biosynthesis; Caspase 8 - metabolism; Enzyme Activation - physiology; Hematologic and hematopoietic diseases; Hodgkin Disease - metabolism; Hodgkin's lymphoma; Humans; Immunohistochemistry; Investigative techniques, diagnostic techniques (general aspects); Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoma, Large B-Cell, Diffuse - metabolism; Medical sciences; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques
• ISSN: 0309-0167; 1365-2559
• DOI: 10.1111/j.1365-2559.2007.02882.x

Aims:  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. Methods and 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.