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VISCO, C; LI, Y; D'AMORE, Esg; MONTES-MORENO, S; DYBKAER, K; CHIU, A; TAM, W; ORAZI, A; ZU, Y; BHAGAT, G; WINTER, J. N; WANG, H.-Y; XU-MONETTE, Z. Y; O'NEILL, S; DUNPHY, C. H; HSI, E. D; ZHAO, X. F; GO, R. S; CHOI, Wwl; ZHOU, F; CZADER, M; TONG, J; ZHAO, X; MIRANDA, R. N; KRIEKEN, Jh Van; HUANG, Q; AI, W; ETZELL, J; PONZONI, M; FERRERI, Ajm; PIRIS, M. A; MØLLER, M. B; BUESO-RAMOS, C. E; MEDEIROS, U; GREEN, T. M; WU, L; YOUNG, K. H; LI, Y; TZANKOV, A; WEN, W; LIU, W-M; KAHL, B. S
Leukemia, 09/2012, Volume: 26, Issue: 9Journal Article
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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