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Article: Comprehensive gene expression profiling and immunohistochemical studies support application of immunophenotypic algorithm for molecular subtype classification in diffuse large B-cell lymphoma: a report from the International DLBCL Rituximab-CHOP Consortium Program Study

TitleComprehensive gene expression profiling and immunohistochemical studies support application of immunophenotypic algorithm for molecular subtype classification in diffuse large B-cell lymphoma: a report from the International DLBCL Rituximab-CHOP Consortium Program Study
Authors
KeywordsABC-DLBCL
BCL6
CD10
Diffuse large B-cell lymphoma
FOXP1
Issue Date2012
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/leu
Citation
Leukemia, 2012, v. 26 n. 9, p. 2103-2113 How to Cite?
AbstractGene expression profiling (GEP) has stratified diffuse large B-cell lymphoma (DLBCL) into molecular subgroups that correspond to different stages of lymphocyte development-namely germinal center B-cell like and activated B-cell like. This classification has prognostic significance, but GEP is expensive and not readily applicable into daily practice, which has lead to immunohistochemical algorithms proposed as a surrogate for GEP analysis. We assembled tissue microarrays from 475 de novo DLBCL patients who were treated with rituximab-CHOP chemotherapy. All cases were successfully profiled by GEP on formalin-fixed, paraffin-embedded tissue samples. Sections were stained with antibodies reactive with CD10, GCET1, FOXP1, MUM1 and BCL6 and cases were classified following a rationale of sequential steps of differentiation of B cells. Cutoffs for each marker were obtained using receiver-operating characteristic curves, obviating the need for any arbitrary method. An algorithm based on the expression of CD10, FOXP1 and BCL6 was developed that had a simpler structure than other recently proposed algorithms and 92.6% concordance with GEP. In multivariate analysis, both the International Prognostic Index and our proposed algorithm were significant independent predictors of progression-free and overall survival. In conclusion, this algorithm effectively predicts prognosis of DLBCL patients matching GEP subgroups in the era of rituximab therapy.
Persistent Identifierhttp://hdl.handle.net/10722/160064
ISSN
2015 Impact Factor: 12.104
2015 SCImago Journal Rankings: 5.142
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorVisco, Cen_US
dc.contributor.authorLi, Yen_US
dc.contributor.authorXu-Monette, ZYen_US
dc.contributor.authorMiranda, RNen_US
dc.contributor.authorGreen, TMen_US
dc.contributor.authorLi, Yen_US
dc.contributor.authorTzankov, Aen_US
dc.contributor.authorWen, Wen_US
dc.contributor.authorLiu, WMen_US
dc.contributor.authorKahl, BSen_US
dc.contributor.authord'Amore, ESGen_US
dc.contributor.authorMontes-Moreno, Sen_US
dc.contributor.authorDybkaer, Ken_US
dc.contributor.authorChiu, Aen_US
dc.contributor.authorTam, Wen_US
dc.contributor.authorOrazi, Aen_US
dc.contributor.authorZu, Yen_US
dc.contributor.authorBhagat, Gen_US
dc.contributor.authorWinter, JNen_US
dc.contributor.authorWang, HYen_US
dc.contributor.authorO'Neill, Sen_US
dc.contributor.authorDunphy, CHen_US
dc.contributor.authorHsi, EDen_US
dc.contributor.authorZhao, XFen_US
dc.contributor.authorGo, RSen_US
dc.contributor.authorChoi, WWLen_US
dc.contributor.authorZhou, Fen_US
dc.contributor.authorCzader, Men_US
dc.contributor.authorTong, Jen_US
dc.contributor.authorZhao, Xen_US
dc.contributor.authorvan Krieken, JHen_US
dc.contributor.authorHuang, Qen_US
dc.contributor.authorAi, Wen_US
dc.contributor.authorEtzell, Jen_US
dc.contributor.authorPonzoni, Men_US
dc.contributor.authorFerreri, AJMen_US
dc.contributor.authorPiris, MAen_US
dc.contributor.authorMoller, MBen_US
dc.contributor.authorBueso-Ramos, CEen_US
dc.contributor.authorMedeiros, LJen_US
dc.contributor.authorWu, Len_US
dc.contributor.authorYoung, KH-
dc.date.accessioned2012-08-16T06:02:14Z-
dc.date.available2012-08-16T06:02:14Z-
dc.date.issued2012en_US
dc.identifier.citationLeukemia, 2012, v. 26 n. 9, p. 2103-2113en_US
dc.identifier.issn0887-6924en_US
dc.identifier.urihttp://hdl.handle.net/10722/160064-
dc.description.abstractGene expression profiling (GEP) has stratified diffuse large B-cell lymphoma (DLBCL) into molecular subgroups that correspond to different stages of lymphocyte development-namely germinal center B-cell like and activated B-cell like. This classification has prognostic significance, but GEP is expensive and not readily applicable into daily practice, which has lead to immunohistochemical algorithms proposed as a surrogate for GEP analysis. We assembled tissue microarrays from 475 de novo DLBCL patients who were treated with rituximab-CHOP chemotherapy. All cases were successfully profiled by GEP on formalin-fixed, paraffin-embedded tissue samples. Sections were stained with antibodies reactive with CD10, GCET1, FOXP1, MUM1 and BCL6 and cases were classified following a rationale of sequential steps of differentiation of B cells. Cutoffs for each marker were obtained using receiver-operating characteristic curves, obviating the need for any arbitrary method. An algorithm based on the expression of CD10, FOXP1 and BCL6 was developed that had a simpler structure than other recently proposed algorithms and 92.6% concordance with GEP. In multivariate analysis, both the International Prognostic Index and our proposed algorithm were significant independent predictors of progression-free and overall survival. In conclusion, this algorithm effectively predicts prognosis of DLBCL patients matching GEP subgroups in the era of rituximab therapy.-
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/leu-
dc.relation.ispartofLeukemiaen_US
dc.subjectABC-DLBCL-
dc.subjectBCL6-
dc.subjectCD10-
dc.subjectDiffuse large B-cell lymphoma-
dc.subjectFOXP1-
dc.titleComprehensive gene expression profiling and immunohistochemical studies support application of immunophenotypic algorithm for molecular subtype classification in diffuse large B-cell lymphoma: a report from the International DLBCL Rituximab-CHOP Consortium Program Studyen_US
dc.typeArticleen_US
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1476-5551 (Electronic) 0887-6924 (Linkin&volume=&spage=&epage=&date=2012&atitle=Comprehensive+gene+expression+profiling+and+immunohistochemical+studies+support+application+of+immunophenotypic+algorithm+for+molecular+subtype+classification+in+diffuse+large+B-cell+lymphoma:+a+report+from+the+International+DLBCL+Rituximab-CHOP+Consortium+Program+Studyen_US
dc.identifier.emailChoi, WWL: choiwl@hkucc.hku.hken_US
dc.identifier.emailYoung, KH: khyoung@mdanderson.org-
dc.identifier.authorityChoi, WL=rp00247en_US
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/leu.2012.83-
dc.identifier.pmid22437443-
dc.identifier.scopuseid_2-s2.0-84865865930-
dc.identifier.hkuros205373en_US
dc.identifier.volume26-
dc.identifier.issue9-
dc.identifier.spage2103-
dc.identifier.epage2113-
dc.identifier.isiWOS:000308342900016-
dc.publisher.placeUnited Kingdom-
dc.identifier.citeulike10601578-

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