The New England journal of medicine
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.
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
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.
Lenz, G; Wright, G; Dave, S S; Xiao, W; Powell, J; Zhao, H; Xu, W; Tan, B; Goldschmidt, N; Iqbal, Javeed; Vose, Julie M.; Bast, M; Fu, Kai; Weisenburger, D D.; Greiner, T C; Armitage, James O.; Kyle, A; May, L; Gascoyne, R D; Connors, J M; Troen, G; Holte, H; Kvaloy, S; Dierickx, D; Verhoef, G; Delabie, J; Smeland, E B; Jares, P; Martinez, A; Lopez-Guillermo, A; Montserrat, E; Campo, E; Braziel, R M; Miller, T P; Rimsza, L M; Cook, J R; Pohlman, B; Sweetenham, J; Tubbs, R R; Fisher, R I; Hartmann, E; Rosenwald, A; Ott, G; Muller-Hermelink, H-K; Wrench, D; Lister, T A; Jaffe, E S; Wilson, W H; Chan, W C.; and Staudt, L M, "Stromal gene signatures in large-B-cell lymphomas." (2008). Journal Articles: Pathology and Microbiology. 32.