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

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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
AuthorsVisco, C12 19
Li, Y20
Xu-Monette, ZY19
Miranda, RN19
Green, TM7
Li, Y8
Tzankov, A3
Wen, W20
Liu, WM20
Kahl, BS25
d'Amore, ESG12
Montes-Moreno, S2
Dybkaer, K
Chiu, A23
Tam, W4
Orazi, A4
Zu, Y26
Bhagat, G18
Winter, JN16
Wang, HY11
O'Neill, S13
Dunphy, CH13
Hsi, ED24
Zhao, XF5
Go, RS27
Choi, WWL1
Zhou, F15
Czader, M6
Tong, J10
Zhao, X10
van Krieken, JH21
Huang, Q14
Ai, W22
Etzell, J22
Ponzoni, M9
Ferreri, AJM9
Piris, MA2
Moller, MB
Bueso-Ramos, CE19
Medeiros, LJ19
Wu, L20
Young, KH19
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
CitationLeukemia, 2012, v. 26 n. 9, p. 2103-2113 [How to Cite?]
DOI: http://dx.doi.org/10.1038/leu.2012.83
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.
ISSN0887-6924
2011 Impact Factor: 9.561
2011 SCImago Journal Rankings: 1.237
DOIhttp://dx.doi.org/10.1038/leu.2012.83
DC Field
Value
dc.contributor.authorVisco, C
dc.contributor.authorLi, Y
dc.contributor.authorXu-Monette, ZY
dc.contributor.authorMiranda, RN
dc.contributor.authorGreen, TM
dc.contributor.authorLi, Y
dc.contributor.authorTzankov, A
dc.contributor.authorWen, W
dc.contributor.authorLiu, WM
dc.contributor.authorKahl, BS
dc.contributor.authord'Amore, ESG
dc.contributor.authorMontes-Moreno, S
dc.contributor.authorDybkaer, K
dc.contributor.authorChiu, A
dc.contributor.authorTam, W
dc.contributor.authorOrazi, A
dc.contributor.authorZu, Y
dc.contributor.authorBhagat, G
dc.contributor.authorWinter, JN
dc.contributor.authorWang, HY
dc.contributor.authorO'Neill, S
dc.contributor.authorDunphy, CH
dc.contributor.authorHsi, ED
dc.contributor.authorZhao, XF
dc.contributor.authorGo, RS
dc.contributor.authorChoi, WWL
dc.contributor.authorZhou, F
dc.contributor.authorCzader, M
dc.contributor.authorTong, J
dc.contributor.authorZhao, X
dc.contributor.authorvan Krieken, JH
dc.contributor.authorHuang, Q
dc.contributor.authorAi, W
dc.contributor.authorEtzell, J
dc.contributor.authorPonzoni, M
dc.contributor.authorFerreri, AJM
dc.contributor.authorPiris, MA
dc.contributor.authorMoller, MB
dc.contributor.authorBueso-Ramos, CE
dc.contributor.authorMedeiros, LJ
dc.contributor.authorWu, L
dc.contributor.authorYoung, KH
dc.date.accessioned2012-08-16T06:02:14Z
dc.date.available2012-08-16T06:02:14Z
dc.date.issued2012
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.description.natureLink_to_subscribed_fulltext
dc.identifier.citationLeukemia, 2012, v. 26 n. 9, p. 2103-2113 [How to Cite?]
DOI: http://dx.doi.org/10.1038/leu.2012.83
dc.identifier.citeulike10601578
dc.identifier.doihttp://dx.doi.org/10.1038/leu.2012.83
dc.identifier.epage2113
dc.identifier.hkuros205373
dc.identifier.issn0887-6924
2011 Impact Factor: 9.561
2011 SCImago Journal Rankings: 1.237
dc.identifier.issue9
dc.identifier.openurl
dc.identifier.pmid22437443
dc.identifier.scopuseid_2-s2.0-84865865930
dc.identifier.spage2103
dc.identifier.urihttp://hdl.handle.net/10722/160064
dc.identifier.volume26
dc.languageeng
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/leu
dc.publisher.placeUnited Kingdom
dc.relation.ispartofLeukemia
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 Study
dc.typeArticle
Author Affiliations
  1. The University of Hong Kong Li Ka Shing Faculty of Medicine
  2. Hospital Universitario Marqués de Valdecilla
  3. Universitätsspital Basel
  4. Weill Cornell Medical College
  5. University of Maryland School of Medicine
  6. Indiana University School of Medicine Indianapolis
  7. Odense Universitetshospital
  8. null
  9. null
  10. Zhejiang University School of Medicine
  11. University of California, San Diego, School of Medicine
  12. Ospedale San Bortolo
  13. University of North Carolina School of Medicine
  14. City of Hope National Med Center
  15. Southwest Washington Medical Center
  16. Northwestern University Feinberg School of Medicine
  17. Aalborg Sygehus
  18. Columbia University Medical Center
  19. University of Texas M. D. Anderson Cancer Center
  20. Roche Molecular Systems
  21. Radboud University Nijmegen Medical Centre
  22. UCSF School of Medicine
  23. Brigham and Women's Hospital
  24. Cleveland Clinic Foundation
  25. University of Wisconsin Hospital and Clinics
  26. Methodist Hospital Houston
  27. Gundersen Lutheran Medical Center