[HTML][HTML] Stromal gene signatures in large-B-cell lymphomas

G Lenz, G Wright, SS Dave, W Xiao… - … England Journal of …, 2008 - Mass Medical Soc
G Lenz, G Wright, SS Dave, W Xiao, J Powell, H Zhao, W Xu, B Tan, N Goldschmidt, J Iqbal…
New England Journal of Medicine, 2008Mass Medical Soc
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 …
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.
The New England Journal Of Medicine