Utjecaj genskih polimorfizama FcγRIIIa i FcγRIIa receptora te izražaja survivina i kaspaze-3 na prognozu bolesnika s difuznim B-velikostaničnim limfomom liječenih kombinacijom rituksimaba i kemoterapije po shemi CHOP

doctoral thesis

• Author: Zdravko Mitrović; MBZ: 272370
• Mentor: Igor Aurer (mentor)
• Committee member: nije dostupno (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; Zagreb
• Defense date and country: 2009-09-23, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences
• Universal decimal classification (UDC): 61 - Medical sciences

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 Fcγ receptora IIIa (FcγRIIIa) 158 V/F i FcγRIIa 131 H/R s odgovorom na liječenje i preživljenjem što ukazuje da stanična citotoksičnost ovisna o protutijelima putem Fcγ 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.

Abstract (english)

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 Fcγ receptor IIIa (FcγRIIIa) 158 V/F and FcγRIIa 131 H/R polymorphisms and response to treatment or survival, suggesting that antibody dependent cellular cytotoxicity through Fcγ 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.

• Keywords: medicina
• Keywords (english): medicine
• Language: croatian
• URN:NBN: urn:nbn:hr:105:698191
• Study programme: Title: Biomedicine and Health Sciences; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstva (doktor/doktorica znanosti, područje biomedicine i zdravstva)
• Type of resource: Text
• Extent: 73 str.
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-05-05 08:54:50