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Frequent nuclear localization of ICAD and cytoplasmic co‐expression of caspase‐8 and caspase‐3 in human lymphomas
Author(s) -
Xerri Luc,
Palmerini Fabienne,
Devilard Elisabeth,
Defrance Thierry,
Bouabdallah Reda,
Hassoun Jacques,
Birg Françoise
Publication year - 2000
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/1096-9896(2000)9999:9999<::aid-path685>3.0.co;2-m
Subject(s) - icad , mantle zone , caspase 3 , mantle cell lymphoma , biology , caspase , apoptosis , cytoplasm , reed–sternberg cell , microbiology and biotechnology , cancer research , lymphoma , pathology , programmed cell death , germinal center , b cell , immunology , medicine , antibody , biochemistry , hodgkin lymphoma
Lymphoma cells often display in vitro resistance to FAS‐induced apoptosis, in which caspases act as crucial cell death effectors. Following FAS stimulation, caspase‐8 activates caspase‐3, which in turn activates the caspase‐activated DNAse (CAD) by proteolysis of its inhibitor (ICAD). To investigate the mechanism of FAS resistance, the expression of caspase‐8 was analysed by immunohistochemistry, together with that of the substrates caspase‐3 and ICAD, in 52 representative samples from non Hodgkin's lymphoma (NHL), 12 from Hodgkin's disease (HD), and eight benign lymphoid tissues. In benign tissues, caspase‐8 was co‐expressed with caspase‐3 in the cytoplasm in germinal centre (GC) cells and was co‐expressed with ICAD in the nuclei of the mantle and marginal zone cells. ICAD expression was weak or absent in GC cells. Cytoplasmic staining for both caspase‐8 and caspase‐3 was present in 11/12 cases of diffuse large cell B‐NHL. Caspase‐8 positivity was nuclear and cytoplasmic in 9/9 follicular NHLs, in 5/5 mantle cell NHLs and in 6/6 marginal zone NHLs. Five out of six peripheral T‐cell NHLs expressed cytoplasmic caspase‐8. Ten out of the 12 HD cases lacked significant cytoplasmic staining for caspase‐3 and caspase‐8 in the majority of Reed–Sternberg cells. All lymphoma cases exhibited predominant nuclear ICAD positivity. Subcellular fractionation analysis of three lymphoma samples and normal mantle zone cells confirmed that ICAD and caspase‐8 were at least partly localized in the nucleus. These results show that the profile of caspase‐8 expression is correlated with histological lymphoma subtypes; that caspase‐8 is co‐expressed with caspase‐3 in GC cells and their neoplastic counterparts; that ICAD has an immunohistochemical nuclear localization in vivo ; and that caspase‐8 and ICAD can be co‐expressed in the nuclei of mantle zone and marginal zone cells; their unexpected nuclear localization allows a reappraisal of the biochemical cascade of caspase activation. Copyright © 2000 John Wiley & Sons, Ltd.