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Recent studies provide convincing evidence that a combined immunohistochemical or fluorescence  in situ  hybridization (FISH) score of MYC, BCL2, BCL6 proteins and  MYC  translocations predicted outcome in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). However, by far, all these researches are based on Western populations. Therefore, we investigate the prognostic relevance of MYC-, BCL2- and BCL6-rearrangements and protein expression by immunohistochemistry and FISH from 336  de novo  DLBCL, NOS treated with CHOP or R-CHOP. Breaks in  MYC  and  BCL6 , and fusion in  IGH/BCL2  were detected in 9.7%, 20.0%, and 11.1% of the cases, respectively, and were not significantly associated with clinical outcomes. Protein overexpression of MYC (≥40%), BCL2 (≥70%) and BCL6 (≥50%) was encountered in 51%, 51% and 36% of the tumors, respectively. On the basis of MYC, BCL2 and BCL6 expression, double-hit scores (DHSs) and triple-hit score (THS) were assigned to all patients with DLBCL. Patients with high MYC/BCL2 DHS, high MYC/BCL6 DHS and high THS had multiple adverse prognostic factors including high LDH level, poor performance status, advanced clinical stage, high International Prognostic Index (IPI) score, and non-germinal center B-cell. In univariate analysis, high MYC/BCL2 DHS, high MYC/BCL6 DHS and high THS were associated with inferior OS and PFS in both CHOP and R-CHOP cohorts ( P <0.05). The highly significant correlations with OS and PFS were maintained in multivariate models that controlled for IPI ( P <0.05). DLBCLs with high DHSs and high THS share the clinical features and poor prognosis of double-hit lymphoma ( P >0.05). These data together suggest that the immunohistochemical DHSs and THS defined a large subset of DLBCLs with double-hit biology and was strongly associated with poor outcome in patients treated with R-CHOP or CHOP.

plos one

MYC Expression in Concert with BCL2 and BCL6 Expression Predicts Outcome in Chinese Patients with Diffuse Large B-Cell Lymphoma, Not Otherwise Specified