Prognostic significance and phenotypic manifestations of MYC/BCL2 protein expression in diffuse large B-cell lymphoma (DLBCL) with extranodal organ involvement: a report of the International DLBCL Rituximab-CHOP Consortium Program Study

Abstract

BACKGROUND: In DLBCL, multiple extranodal sites of involvement and MYC/BCL2 translocations (double hit lymphoma) are associated with a poor clinical outcome. The association between the pattern of extranodal involvement and MYC and BCL2 protein expression, as well as the prognostic significance of expression, are unknown. METHODS: We analyzed the clinical data of 487 DLBCL patients treated with R-CHOP. Immunohistochemical (IHC) studies were performed on paraffin-embedded tissue samples for MYC and BCL2. A double-hit score (DHS) of 0, 1, or 2 was assigned to all patients based on protein expression of MYC and BCL2. Those with both MYC and BCL2 expression were DHS 2, with MYC or BCL2 was DHS 1, and neither was DHS 0. Cell-of-origin classification was achieved by combining gene expression profiling (GEP) and IHC data with GEP as the gold standard. Patient characteristics were compared using Fisher's exact test. Survival analyses were performed using Kaplan-Meier curves and compared using log-rank test. The Cox proportional regression model was used for mult…