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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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Date
2012-09
Authors
Visco, C
Li, Y
Xu-Monette, ZY
Miranda, RN
Green, TM
Li, Y
Tzankov, A
Wen, W
Liu, W-M
Kahl, BS
d'Amore, ESG
Montes-Moreno, S
Dybkær, K
Chiu, A
Tam, W
Orazi, A
Zu, Y
Bhagat, G
Winter, JN
Wang, H-Y
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
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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.
Type
Journal article
Subject
Humans
Cyclophosphamide
Vincristine
Doxorubicin
Prednisone
Antineoplastic Combined Chemotherapy Protocols
Immunoenzyme Techniques
Prognosis
Oligonucleotide Array Sequence Analysis
Tissue Array Analysis
Survival Rate
Gene Expression Profiling
Immunophenotyping
Algorithms
Middle Aged
Female
Male
Lymphoma, Large B-Cell, Diffuse
Antibodies, Monoclonal, Murine-Derived
Biomarkers, Tumor
Rituximab
Permalink
https://hdl.handle.net/10161/19324
Published Version (Please cite this version)
10.1038/leu.2012.83
Publication Info
Visco, C; Li, Y; Xu-Monette, ZY; Miranda, RN; Green, TM; Li, Y; ... 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, 26(9). pp. 2103-2113. 10.1038/leu.2012.83. Retrieved from https://hdl.handle.net/10161/19324.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

Xu-Monette

Zijun Yidan Xu-Monette

Assistant Professor in Pathology
My research efforts have been focused on identifying prognostic and therapeutic biomarkers in B-cell lymphoma. My research interests also include investigation of molecular and immune mechanisms underlying the poor clinical outcomes of lymphoma, the pathogenesis and evolution of drug resistant clones, and development of novel therapies for aggressive B-cell lymphoma.
Young

Ken H Young

Professor of Pathology
I am a clinically-oriented diagnostic physician with clinical expertise in the pathologic diagnosis of hematologic cancers including tumors of the bone marrow, lymphoid tissue, spleen and pre-malignant hematologic conditions. Another area of interest is blood cancer classification with molecular and genetic profiling. In my research program, we focus on molecular mechanisms of tumor progression, cell-of-origin, biomarkers, and novel therapeutic strategies in lymphoma, myeloma and leukemia. In
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