Expression of NFκB/mTORC Pathway Proteins is Associated With Response to CHOP plus Bortezomib (CHOP-B) in a Patient With Angioimmunoblastic Peripheral T-cell Lymphoma (AI-PTCL)

DLBCL patients from developed countries who were treated with R-CHOP. Design: A cohort (n1⁄4732) of patients with DLBCL treated with R-CHOP chemotherapy are included in the International DLBCL Rituximab-CHOP Consortium Program. All cases were diagnosed according to the WHO criteria. DLBCLs transformed from a low-grade B-cell lymphoma or associated with acquired immunodeficiency (e.g. human immunodeficiency virus infection), primary cutaneous DLBCLs, primary central nervous system DLBCLs, and primary mediastinal large B-cell lymphomas were excluded. For the study group we collected clinical data and assessed different biomarkers by immunohistochemistry. We also assessed for genetic abnormalities by fluorescent in situ hybridization, performed mutation analysis, gene expression profiling (GEP) and gene set enrichment analysis (GSEA). Presence of EBV was assessed by in situ hybridization for EBV encoded RNA (EBER). Setting: This study can aid lymphoma specialists in improving risk stratification of DLBCL patients. Results: Twenty-eight (4.0%) patients were positive for EBV with a median age of 60.5 years (add range). No clinical characteristics distinguished patients with EBV+ DLBCL from patients with EBV-negative DLBCL. Genetic aberrations were rarely seen in EBV+ DLBCL. NF-kB p50, phosphoSTAT-3 and CD30 were more commonly expressed in EBV+ DLBCL (P<.05). Significant differences in survival were not observed in patients with EBV+ DLBCL versus EBV-negative DLBCL. CD30 co-expression appeared to confer inferior outcome although statistical significance was not achieved. GEP showed a unique expression signature in EBV+ DLBCL and GSEA revealed enhanced activity of the NF-kB and JAK/STAT pathways. Conclusions: The clinical characteristics of patients with EBV+ DLBCL versus EBV-negative DLBCL are similar. EBV infection per se does not predict a worse outcome. CD30 expression is more common in EBV+ DLBCL and, when present, is associated with an adverse outcome. EBV+ DLBCL has a unique genetic signature.