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.
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 articleSubject
HumansCyclophosphamide
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
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https://hdl.handle.net/10161/19324Published Version (Please cite this version)
10.1038/leu.2012.83Publication 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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Show full item recordScholars@Duke
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.
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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