High levels of topoisomerase IIalpha protein expression in diffuse large B-cell lymphoma are associated with high proliferation, germinal center immunophenotype, and response to treatment

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dc.contributor.authorPentheroudakis, G.en
dc.contributor.authorGoussia, A.en
dc.contributor.authorVoulgaris, E.en
dc.contributor.authorNikolaidis, K.en
dc.contributor.authorIoannidou, E.en
dc.contributor.authorPapoudou-Bai, A.en
dc.contributor.authorGrepi, K.en
dc.contributor.authorKanavaros, P.en
dc.contributor.authorPavlidis, N.en
dc.contributor.authorBai, M.en
dc.date.accessioned2015-11-24T19:13:47Z
dc.date.available2015-11-24T19:13:47Z
dc.identifier.issn1029-2403-
dc.identifier.urihttps://olympias.lib.uoi.gr/jspui/handle/123456789/21224
dc.rightsDefault Licence-
dc.subjectAdulten
dc.subjectAgeden
dc.subjectAged, 80 and overen
dc.subjectAntigens, Neoplasm/genetics/*metabolismen
dc.subjectAntineoplastic Combined Chemotherapy Protocols/*therapeutic useen
dc.subjectCell Cycle Proteins/metabolismen
dc.subjectCell Differentiationen
dc.subject*Cell Proliferationen
dc.subjectCyclophosphamide/therapeutic useen
dc.subjectDNA Topoisomerases, Type II/genetics/*metabolismen
dc.subjectDNA-Binding Proteins/genetics/*metabolismen
dc.subjectDoxorubicin/therapeutic useen
dc.subjectFemaleen
dc.subjectGene Amplificationen
dc.subjectGerminal Center/drug effects/*enzymology/immunologyen
dc.subjectHumansen
dc.subjectImmunoenzyme Techniquesen
dc.subjectImmunophenotypingen
dc.subjectIn Situ Hybridization, Fluorescenceen
dc.subjectLymphoma, Large B-Cell, Diffuse/drug therapy/*enzymology/pathologyen
dc.subjectMaleen
dc.subjectMiddle Ageden
dc.subjectNeoplasm Stagingen
dc.subjectPrednisolone/therapeutic useen
dc.subjectRetrospective Studiesen
dc.subjectSurvival Rateen
dc.subjectTreatment Outcomeen
dc.subjectVincristine/therapeutic useen
dc.titleHigh levels of topoisomerase IIalpha protein expression in diffuse large B-cell lymphoma are associated with high proliferation, germinal center immunophenotype, and response to treatmenten
heal.abstractGene copy number and protein expression of topoisomerase IIalpha were correlated to benefit from anthracyclines in various tumors. A retrospective series of 69 patients with DLBCL managed with CHOP chemotherapy were studied for immunohistochemical TopoIIalpha expression and numerical gene abnormalities by fluorescent in situ hybridization (FISH). The results were analyzed in relation to the expression of cell cycle proteins (Ki67, p53, HDM2, p21, p14, pRb, p16, and cyclins A, B1, D1, D2, D3, and E) and BCL6/CD10/MUM1/CD138 B-cell differentiation immunophenotype and outcome. High levels of TopoIIalpha protein were found in 91% of DLBCL cases. No evidence of TopoIIalpha gene amplification or deletion was found. The TopoIIalpha expression showed significant positive correlations with the proliferation index Ki67 (p = 0.002), cell cycle proteins pRb and cyclin D2 (p = 0.018 and p = 0.028, respectively), and the germinal center proteins bcl6 and CD10 (p = 0.010 and p < 0.0001, respectively). TopoIIalpha expression was significantly higher in germinal center B-cell like (GCB) DLBCL than in non-germinal center B-cell like (non-GCB) DLBCL (p = 0.048). TopoIIalpha protein was significantly associated with response to chemotherapy (chi(2), p = 0.024), but not with relapse-free or overall survival (p = 0.5). On multivariate analysis, only stage of disease retained independent prognostic significance (HR 0.33 for early stage, p = 0.008). Although TopoIIa gene copy number abnormalities were not found in DLBCL, high levels of protein expression are associated with GCB-cell differentiation immunophenotype, high proliferation, and response to treatment.en
heal.accesscampus-
heal.fullTextAvailabilityTRUE-
heal.identifier.primary10.3109/10428194.2010.483749-
heal.identifier.secondaryhttp://www.ncbi.nlm.nih.gov/pubmed/20497003-
heal.identifier.secondaryhttp://informahealthcare.com/doi/abs/10.3109/10428194.2010.483749-
heal.journalNameLeuk Lymphomaen
heal.journalTypepeer-reviewed-
heal.languageen-
heal.publicationDate2010-
heal.recordProviderΠανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικήςel
heal.typejournalArticle-
heal.type.elΆρθρο Περιοδικούel
heal.type.enJournal articleen

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