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

C. Visco, Y. Li, Z. Y. Xu-Monette, R. N. Miranda, T. M. Green, Y. Li, A. Tzankov, W. Wen, W. M. Liu, B. S. Kahl, E. S.G. D'Amore, S. Montes-Moreno, K. Dybkær, A. Chiu, W. Tam, A. Orazi, Y. Zu, G. Bhagat, J. N. Winter, H. Y. WangS. O'Neill, C. H. Dunphy, E. D. Hsi, X. F. Zhao, R. S. Go, W. W.L. Choi, F. Zhou, M. Czader, J. Tong, X. Zhao, J. H. Van Krieken, Q. Huang, W. Ai, J. Etzell, M. Ponzoni, A. J.M. Ferreri, M. A. Piris, M. B. Møller, C. E. Bueso-Ramos, L. J. Medeiros, L. Wu, K. H. Young

Research output: Contribution to journalArticlepeer-review

231 Scopus citations

Abstract

Gene 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.

Original languageEnglish (US)
Pages (from-to)2103-2113
Number of pages11
JournalLeukemia
Volume26
Issue number9
DOIs
StatePublished - Sep 2012

Keywords

  • ABC-DLBCL
  • BCL6
  • CD10
  • diffuse large B-cell lymphoma
  • FOXP1
  • GCB-DLBCL

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

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