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Mitrović, Zdravko and Ilić, Ivana and Aurer, Igor and Bašić-Kinda, Sandra and Radman, Ivo and Dotlić, Snježana and Ajduković, Radmila and Labar, Boris (2010) Prognostic Significance of Survivin and Caspase-3 Immunohistochemical Expression in Patients with Diffuse Large B-cell Lymphoma Treated with Rituximab and CHOP. Pathology Oncology Research, [Epub . Abstract Survivin is an inhibitor of apoptosis whose expression may be associated with inferior outcome in patients with diffuse large B-cell lymphoma (DLBCL) treated without rituximab. Caspase-3 is the final caspase of the apoptotic cascade and its pattern of expression may also be related to patients' outcome. In this study we investigated immunohistochemical expression of survivin and caspase-3 (CPP32) in 57 patients with DLBCL treated with rituximab and CHOP (R-CHOP). According to previously published criteria, we separately analyzed correlation of different types of survivin expression with patients' outcome. Nuclear survivin was expressed in only 26% of cases, cytoplasmic survivin was expressed in 81% of cases while application of immunoreactivity scoring system yielded 58% of survivin positive cases. Caspase-3 was expressed in 77% of cases. There were no significant correlations between any type of survivin expression and response to treatment or survival of the patients. The expression of caspase-3 was also not associated with patients' outcome. We conclude that survivin and caspase-3 have no significant prognostic significance in patients with DLBCL treated with R-CHOP. Actions (login required) Downloads Downloads per month over past year
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Mitrović, Zdravko (2009) Utjecaj genskih polimorfizama FcYRIIIa i FcYRIIa receptora te izražaja survivina i kaspaze-3 na prognozu bolesnika s difuznim B-velikostaničnim limfomom liječenih kombinacijom rituksimaba i kemoterapije po shemi CHOP. PhD thesis, Sveučilište u Zagrebu. Croatian abstract Difuzni B-velikostanični limfom (DLBCL) je najčešći ne-Hodgkinov limfom. Standardnim metodama liječenja moguće je izliječiti oko 60% bolesnika, a prognoza ovisi prvenstveno o kliničkim značajkama, sažetim u tzv. međunarodnom prognostičkom indeksu (IPI). Međutim, nema općeprihvaćenih molekulskih i imunohistokemijskih prognostičkih biljega u DLBCL. Cilj ovog rada bio je analizirati prognostički značaj molekularnih i imunohistokemijskih biljega u 60 bolesnika s DLBCL-om liječenih na jedinstven način, kombinacijom rituksimaba i kemoterapije po shemi CHOP ili slične. Nije nađena povezanost polimorfizama FcY receptora IIIa (FcYRIIIa) 158 V/F i FcYRIIa 131 H/R s odgovorom na liječenje i preživljenjem što ukazuje da stanična citotoksičnost ovisna o protutijelima putem FcY receptora nije najznačajniji mehanizam djelovanja rituksimaba u ovoj skupini bolesnika. Imunohistokemijski biljezi diferencijacije i aktivacije, CD10, bcl-6, MUM1, nisu bili od prognostičkog značenja u ispitivanoj skupini bolesnika. Podjela DLBCL-a na GC i non-GC imunofenotip upotrebom algoritma po Hansovoj nije bila povezana s promatranim ishodima. Ovaj nalaz ukazuje da imunohistokemijske metode ne mogu zamijeniti analizu izražaja gena u razlikovanju molekularnih podtipova DLBCL-a- Alternativno, moguće je da rituksimab mijenja prognostičko značenje nekih biljega. Biljezi apoptoze, bcl-2, survivin i kaspaza-3, također nisu bili povezani s promatranim ishodima. Za razliku od toga, izražaj CD43 je bio povezan sa slabijim odgovorom na liječenje i lošijim preživljenjem, neovisno o IPI-u. Čini se da je CD43 vrlo značajan novootkiveni nepovoljni prognostički faktor u bolesnika s DLBCL. English abstract Diffuse large B-cell lymphoma (DLBCL) is the most frequent non-Hodgkin lymphoma. Using standard treatment approaches, about 60% of patients can be cured; prognosis depends primarily on clinical characteristics summarized in the „International Prognostic Index“ (IPI). However, there is no generally accepted molecular or immunohistochemical prognostic marker for DLBCL. The aim of this study was to investigate the prognostic importance of molecular and immunohistochemical markers in 60 patients with DLBCL treated homogenously with rituximab and CHOP or CHOP-like chemotherapy. No correlation was found between FcY receptor IIIa (FcYRIIIa) 158 V/F and FcYRIIa 131 H/R polymorphisms and response to treatment or survival, suggesting that antibody dependent cellular cytotoxicity through FcY receptors is not the most important mechanism of rituximab action in this setting. Immunohistochemical markers of differentiation and activation, CD10, bcl-6 and MUM1, were not of prognostic significance in this group of patients. Classification of DLBCLs in GC and non-GC subtypes according to the algorithm published by Hans and co-workers did not affect the outcomes. This finding suggests that immunohistochemical methods cannot reliably replace gene expression profiling in differentiating between molecular subtypes of DLBCL. Alternatively, it is possible that rituximab may change the prognostic significance of some markers. Apoptosis markers, bcl-2, survivin and caspase-3, were also not associated with outcomes. In contrast, CD43 expression was associated with a lower response rate and inferior survival, independently of IPI. Thus, CD43 seems to be a very important new adverse prognostic marker in patients with DLBCL. Actions (login required)