G Lenz, National Institutes of Health, Bethesda, MD
G Wright, National Institutes of Health, Bethesda, MD
S S Dave, National Institutes of Health, Bethesda, MD
W Xiao, National Institutes of Health, Bethesda, MD
J Powell, National Institutes of Health, Bethesda, MD
H Zhao, National Institutes of Health, Bethesda, MD
W Xu, National Institutes of Health, Bethesda, MD
B Tan, National Institutes of Health, Bethesda, MD
N Goldschmidt, National Institutes of Health, Bethesda, MD
Javeed Iqbal, University of Nebraska Medical CenterFollow
Julie M. Vose, University of Nebraska Medical CenterFollow
M Bast, University of Nebraska Medical CenterFollow
Kai Fu, University of Nebraska Medical CenterFollow
D D. Weisenburger, University of Nebraska Medical Center
T C Greiner, University of Nebraska Medical CenterFollow
James O. Armitage, University of Nebraska Medical CenterFollow
A Kyle, British Columbia Cancer Agency
L May, British Columbia Cancer Agency
R D Gascoyne, British Columbia Cancer Agency
J M Connors, British Columbia Cancer Agency
G Troen, University of Oslo
H Holte, University of Oslo
S Kvaloy, University of Oslo
D Dierickx, University of Leuven, Belgium
G Verhoef, University of Leuven, Belgium
J Delabie, University of Oslo
E B Smeland, University of Oslo
P Jares, University of Barcelona
A Martinez, University of Barcelona
A Lopez-Guillermo, University of Barcelona
E Montserrat, University of Barcelona
E Campo, University of Barcelona
R M Braziel, Oregon Health and Science University
T P Miller, Southwest Oncology Group
L M Rimsza, Southwest Oncology Group
J R Cook, Southwest Oncology Group
B Pohlman, Cleveland Clinic Taussig Cancer Institute
J Sweetenham, Cleveland Clinic Taussig Cancer Institute
R R Tubbs, Southwest Oncology Group
R I Fisher, Southwest Oncology Group
E Hartmann, University of Würzburg
A Rosenwald, University of Würzburg
G Ott, University of Würzburg
H-K Muller-Hermelink, University of Würzburg
D Wrench, Bartholomew's Hospital, London
T A Lister, Bartholomew's Hospital, London
E S Jaffe, National Institutes of Health, Bethesda, MD
W H Wilson, National Institutes of Health, Bethesda, MD
W C. Chan, University of Nebraska Medical Center
L M Staudt, National Institutes of Health, Bethesda, MD

Document Type

Article

Journal Title

The New England journal of medicine

Publication Date

Winter 11-27-2008

Volume

359

Abstract

BACKGROUND: The addition of rituximab to combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), or R-CHOP, has significantly improved the survival of patients with diffuse large-B-cell lymphoma. Whether gene-expression signatures correlate with survival after treatment of diffuse large-B-cell lymphoma is unclear.

METHODS: We profiled gene expression in pretreatment biopsy specimens from 181 patients with diffuse large-B-cell lymphoma who received CHOP and 233 patients with this disease who received R-CHOP. A multivariate gene-expression-based survival-predictor model derived from a training group was tested in a validation group.

RESULTS: A multivariate model created from three gene-expression signatures--termed "germinal-center B-cell," "stromal-1," and "stromal-2"--predicted survival both in patients who received CHOP and patients who received R-CHOP. The prognostically favorable stromal-1 signature reflected extracellular-matrix deposition and histiocytic infiltration. By contrast, the prognostically unfavorable stromal-2 signature reflected tumor blood-vessel density.

CONCLUSIONS: Survival after treatment of diffuse large-B-cell lymphoma is influenced by differences in immune cells, fibrosis, and angiogenesis in the tumor microenvironment.

MeSH Headings

Antibodies, Monoclonal, Antibodies, Monoclonal, Murine-Derived, Antineoplastic Combined Chemotherapy Protocols, Cyclophosphamide, Disease Progression, Doxorubicin, Extracellular Matrix, Gene Expression, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Genes, MHC Class II, Germinal Center, Humans, Immunologic Factors, Kaplan-Meier Estimate, Lymphoma, Large B-Cell, Diffuse, Middle Aged, Multivariate Analysis, Neovascularization, Pathologic, Prednisone, Prognosis, Rituximab, Stromal Cells, Vincristine

ISSN

1533-4406

Rights

From the New England Journal of Medicine, Lenz G, Wright G, Dave SS, et al. Stromal gene signatures in large-B-cell lymphomas, 359, 2313-2323 . Copyright © (2008) Massachusetts Medical Society. Reprinted with permission.

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