期刊
LEUKEMIA
卷 26, 期 9, 页码 2103-2113出版社
SPRINGERNATURE
DOI: 10.1038/leu.2012.83
关键词
diffuse large B-cell lymphoma; ABC-DLBCL; GCB-DLBCL; CD10; BCL6; FOXP1
资金
- San Bortolo Hospital, Vicenza, Italy
- University of Texas MD Anderson Cancer Center
- University of Texas MD Anderson Cancer Center Institutional R and D Fund
- Institutional Research Grant Award
- MD Anderson Cancer Center SPORE Research Development Program Award
- Gundersen Lutheran Medical Foundation Award and Forward Lymphoma Fund
- Zurich Stiftung zur Krebsbekaempfung
- NCI/NIH [R01CA138688, 1RC1CA146299]
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.
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