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 journalArticle

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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
Pages (from-to)2103-2113
Number of pages11
JournalLeukemia
Volume26
Issue number9
DOIs
Publication statusPublished - Sep 2012

Fingerprint

Lymphoma, Large B-Cell, Diffuse
Gene Expression Profiling
B-Lymphocytes
Germinal Center
ROC Curve
Paraffin
Formaldehyde
Disease-Free Survival
Rituximab
Multivariate Analysis
Lymphocytes
Drug Therapy
Antibodies

Keywords

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

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

Cite this

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

In: Leukemia, Vol. 26, No. 9, 09.2012, p. 2103-2113.

Research output: Contribution to journalArticle

Visco, C, Li, Y, Xu-Monette, ZY, Miranda, RN, Green, TM, Li, Y, Tzankov, A, Wen, W, Liu, WM, Kahl, BS, D'Amore, ESG, Montes-Moreno, S, Dybkær, K, Chiu, A, Tam, W, Orazi, A, Zu, Y, Bhagat, G, Winter, JN, Wang, HY, O'Neill, S, Dunphy, CH, Hsi, ED, Zhao, XF, Go, RS, Choi, WWL, Zhou, F, Czader, M, Tong, J, Zhao, X, Van Krieken, JH, Huang, Q, Ai, W, Etzell, J, Ponzoni, M, Ferreri, AJM, Piris, MA, Møller, MB, Bueso-Ramos, CE, Medeiros, LJ, Wu, L & Young, KH 2012, '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', Leukemia, vol. 26, no. 9, pp. 2103-2113. https://doi.org/10.1038/leu.2012.83
Visco, C. ; Li, Y. ; Xu-Monette, Z. Y. ; Miranda, R. N. ; Green, T. M. ; Li, Y. ; Tzankov, A. ; Wen, W. ; Liu, W. M. ; Kahl, B. S. ; D'Amore, E. S G ; Montes-Moreno, S. ; Dybkær, K. ; Chiu, A. ; Tam, W. ; Orazi, A. ; Zu, Y. ; Bhagat, G. ; Winter, J. N. ; Wang, H. Y. ; O'Neill, S. ; Dunphy, C. H. ; Hsi, E. D. ; Zhao, X. F. ; Go, R. S. ; Choi, W. W L ; Zhou, F. ; Czader, M. ; Tong, J. ; Zhao, X. ; Van Krieken, J. H. ; Huang, Q. ; Ai, W. ; Etzell, J. ; Ponzoni, M. ; Ferreri, A. J M ; Piris, M. A. ; Møller, M. B. ; Bueso-Ramos, C. E. ; Medeiros, L. J. ; Wu, L. ; Young, K. H. / 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. In: Leukemia. 2012 ; Vol. 26, No. 9. pp. 2103-2113.
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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.",
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author = "C. Visco and Y. Li and Xu-Monette, {Z. Y.} and Miranda, {R. N.} and Green, {T. M.} and Y. Li and A. Tzankov and W. Wen and Liu, {W. M.} and Kahl, {B. S.} and D'Amore, {E. S G} and S. Montes-Moreno and K. Dybk{\ae}r and A. Chiu and W. Tam and A. Orazi and Y. Zu and G. Bhagat and Winter, {J. N.} and Wang, {H. Y.} and S. O'Neill and Dunphy, {C. H.} and Hsi, {E. D.} and Zhao, {X. F.} and Go, {R. S.} and Choi, {W. W L} and F. Zhou and M. Czader and J. Tong and X. Zhao and {Van Krieken}, {J. H.} and Q. Huang and W. Ai and J. Etzell and M. Ponzoni and Ferreri, {A. J M} and Piris, {M. A.} and M{\o}ller, {M. B.} and Bueso-Ramos, {C. E.} and Medeiros, {L. J.} and L. Wu and Young, {K. H.}",
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T1 - Comprehensive gene expression profiling and immunohistochemical studies support application of immunophenotypic algorithm for molecular subtype classification in diffuse large B-cell lymphoma

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AU - Visco, C.

AU - Li, Y.

AU - Xu-Monette, Z. Y.

AU - Miranda, R. N.

AU - Green, T. M.

AU - Li, Y.

AU - Tzankov, A.

AU - Wen, W.

AU - Liu, W. M.

AU - Kahl, B. S.

AU - D'Amore, E. S G

AU - Montes-Moreno, S.

AU - Dybkær, K.

AU - Chiu, A.

AU - Tam, W.

AU - Orazi, A.

AU - Zu, Y.

AU - Bhagat, G.

AU - Winter, J. N.

AU - Wang, H. Y.

AU - O'Neill, S.

AU - Dunphy, C. H.

AU - Hsi, E. D.

AU - Zhao, X. F.

AU - Go, R. S.

AU - Choi, W. W L

AU - Zhou, F.

AU - Czader, M.

AU - Tong, J.

AU - Zhao, X.

AU - Van Krieken, J. H.

AU - Huang, Q.

AU - Ai, W.

AU - Etzell, J.

AU - Ponzoni, M.

AU - Ferreri, A. J M

AU - Piris, M. A.

AU - Møller, M. B.

AU - Bueso-Ramos, C. E.

AU - Medeiros, L. J.

AU - Wu, L.

AU - Young, K. H.

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KW - FOXP1

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