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

This journal issue is proceedings of ASH Conference 2012Open Access JournalOral Sessions - 622. Non-Hodgkin Lymphoma - Biology, excluding Therapy: MYC And Others, The Usual SuspectsBACKGROUND: 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…link_to_OA_fulltex

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

This journal issue is proceedings of ASH Conference 2012Open Access JournalOral Sessions - 622. Non-Hodgkin Lymphoma - Biology, excluding Therapy: MYC And Others, The Usual SuspectsBACKGROUND: 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…link_to_OA_fulltex

The t(14;18)(q32;q21) characterizes a subset of patients with diffuse large-B cell lymphoma of germinal center origin with poor outcome: report from the International DLBCL Rituximab-CHOP Consortium Program Study

Oral Sessions - 622. Non-Hodgkin Lymphoma - Biology, excluding Therapy: Clinical Determinants and MicroenvironmentOpen Access JournalThis journal issue is proceedings of ASH Conference 2011INTRODUCTION: Diffuse large B cell lymphoma (DLBCL) has a highly variable outcome, and individual risk assessment is largely based on clinical features. Gene expression profiling (GEP) stratifies patients into those with germinal center B-cell (GCB) and activated B-cell subtype (ABC) subtype with different prognoses. These groups have been shown to predict prognosis in patients treated with CHOP or R-CHOP. Conversely, the role of other recognized prognostic markers, such as BCL2 gene abnormalities or Bcl2 expression has been questioned in the new therapeutic era. MATERIALS AND METHODS: In 438 patients treated with R-CHOP for de novo DLBCL, we analyzed the tumors by immunohistochemistry for Bcl2 protein expression and by interphase fluorescence in situ hybridization (FISH) for BCL2 translocation and other abnormalities. All cases were successfully studied by GEP. The cutoff for Bcl2 protein expression, 60%, used as prognostic factor was determined using receiver operating characteristic curves. Progression-free survival (PFS) and overall survival (OS) were assessed. RESULTS: The t(14;18)(q32;q21) was detected in 82 cases (18.7%) and BCL2 gains occurred in 63 cases (14.3%). Both t(14;18) and BCL2 gains strongly correlated with higher levels of Bcl2 protein expression (p60%) tumors had significantly inferior PFS in the GCB subgroup (p=0.03), but not in the ABC subgroup (p=0.54). Multivariate analysis revealed that the presence of the t(14;18), but not Bcl2 protein expression, was independent of the International Prognostic Index in predicting outcome of our patients. CONCLUSIONS: Patients with the GCB subtype and t(14;18) exhibit a significantly worse prognosis than patients without t(14;18) when treated with R-CHOP. The assessment of t(14;18) by FISH approach not only functions as a valuable prognosticator for individual risk estimation in GCB-DLBCL patients in addition to the established parameters, but also provides valuable result for therapeutic intervention.link_to_OA_fulltex