CD30-Expression Defines a Novel Subset of Diffuse Large B-Cell Lymphoma with Superior Clinical Outcome: A Report from the International DLBCL Rituximab-CHOP Consortium Program Study
Shimin Hu, Alexander Tzankov, Carlo Visco, Attilio Orazi, Govind Bhagat, Eric E 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: CD30 (TNFSF8), a member of the tumor necrosis factor receptor superfamily originally identified as a marker of Reed-Sternberg and Hodgkin cells in classical Hodgkin lymphoma, is also expressed by several types of non-Hodgkin lymphoma, including anaplastic large cell lymphoma (ALCL), primary mediastinal B-cell lymphoma (PMBCL) and a subset of diffuse large B-cell lymphoma (DLBCL). The prognostic importance of CD30 expression in DLBCL remains unknown.
Design: 461 patients with de novo DLBCL treated with R-CHOP were studied for CD30 expression using tissue microarray immunohistochemistry and the results were correlated with clinicopathologic features, molecular genetic changes, gene expression profiles, and clinical outcome.
Results: CD30 was expressed in 65 (14%) cases of DLBCL. Patients with CD30+ DLBCL had superior 5-year overall survival (CD30+ 79% vs. CD30- 59%, p=0.0013) and progression-free survival (CD30+ 73% vs. CD30- 57%, p=0.0030). The favorable outcome of CD30 expression was maintained in the germinal center B-cell subtype and showed a trend in the activated B-cell subtype. Gene expression profiling of CD30+ DLBCL revealed upregulation of many genes encoding proteins that negatively regulate NF-kB activation and lymphocyte survival, and downregulation of genes involved in B-cell receptor signaling, suggesting a possible molecular basis for the favorable clinical outcome of patients with CD30+ DLBCL.
Conclusions: CD30 expression confers a favorable clinical outcome in patients with de novo DLBCL treated with R-CHOP. The unique gene signature of CD30+ DLBCL and its favorable prognostic impact supports the notion that CD30+ DLBCL could represent a distinct subtype of DLBCL.
Monday, March 4, 2013 1:30 PM
Proffered Papers: Section C, Monday Afternoon