C Visco,
Y Li,
Z Y Xu-Monette,
R N Miranda,
T M Green,
A Tzankov,
W Wen,
W-M Liu,
B S Kahl,
E S G d'Amore, [......],
W Ai,
J Etzell,
M Ponzoni,
A J M Ferreri,
M A Piris,
M B Møller, C E Bueso-Ramos,
L J Medeiros,
L Wu,
K H Young
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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.
Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 03/2012; 26(9):2103-13. · 8.30 Impact Factor
