Prognostic Impact of Myc/Bcl6 Co-Rearrangement and MYC/BCL6 Co-Expression in De Novo Diffuse Large B-Cell Lymphoma: A Report from the International DLBCL Rituximab-CHOP Consortium Program Study
Shimin Hu, Alexander Tzankov, Carlo Visco, Orazi Orazi, Govind Bhagat, Eric D Hsi, Maurilio Ponzoni, Miguel A Piris, Michael B Moller, L Jeffrey Medeiros, Ken H Young. University of Texas MD Anderson Cancer Center, Houston, TX
Background: Myc/Bcl2 double-hit and MYC/BCL2 co-expression define a subset of diffuse large B-cell lymphoma (DLBCL) patients with an aggressive clinical course. However, the prognostic impact of chromosomal alterations involving MYC and BCL6 loci and MYC/BCL6 co-expression in DLBCL is less well known.
Design: 494 patients with de novo DLBCL treated with R-CHOP chemotherapy were studied for Myc, Bcl2, and Bcl6 genetic alterations by florescence in situ hybridization, and MYC, BCL2 and BCL6 expression by immunohistochemistry using tissue microarrays. The results were correlated with cell-of-origin (COO) and clinical outcome. The COO classification was based on gene expression profiles supplemented by immunohistochemistry.
Results: 250 (50.1%) cases were classified as germinal center B-cell like (GCB), 238 (48.2%) were classified as activated B-cell like (ABC), and 6 were unclassifiable. Myc and Bcl6 breaks occurred in 10.3% and 35% of DLBCL cases, respectively. Myc rearrangement demonstrated a GCB predominance (14.1% in GCB vs 6.7% in ABC, p=0.03) whereas Bcl6 rearrangement showed ABC predominance (41.7% in ABC vs 28.7% in GCB, p=0.02). Bcl6 amplification was common in DLBCL (32.0%) and was equally distributed across GCB and ABC subtypes. Myc amplification was rare. Myc/Bcl6 double-hit was observed in 1.7% of DLBCL cases. Myc rearrangement conferred significant adverse prognostic impact in patients with GCB DLBCL (p=0.0007) whereas Bcl6 rearrangement did not correlate with prognosis in DLBCL patients overall or in COO subtypes in the absence or presence of Myc rearrangement. Bcl6 amplification had a trend toward better overall survival in GCB DLBCL (p=0.06). MYC/BCL6 co-expression was seen in half of DLBCL cases. In the absence of BCL2 protein expression, neither MYC nor BCL6 expression, alone or in combination, conferred any prognostic impact in DLBCL or in COO subtypes.
Conclusions: Myc/Bcl6 co-rearrangement is rare whereas MYC/BCL6 co-expression is common in DLBCL. Neither Myc/Bcl6 co-rearrangement nor MYC/BCL6 co-expression confers any significant prognostic impact in DLBCL overall or in COO subtypes in the absence of Bcl2 co-rearrangement or BCL2 co-expression. Hence, the grouping of cases of Myc/Bcl6 co-rearrangement with Myc/Bcl2 co-rearrangement, often referred to as double-hit lymphomas, needs to be reconsidered.
Monday, March 4, 2013 1:00 PM
Poster Session II # 204, Monday Afternoon