CD30 expression defines a novel subset of diffuse large B-cell lymphoma with favorable prognosis and distinct gene expression signature: a report from The International DLBCL Rituximab-CHOP Consortium Program Study

Shimin Hu, Zijun Y. Xu-Monette, Aarthi Balasubramanyam, Ganiraju C. Manyam, Carlo Visco, Alexander Tzankov, Wei-min Liu, Roberto N. Miranda, Li Zhang, Santiago Montes-Moreno, Karen Dybkaer, April Chiu, Attilio Orazi, Youli Zu, Govind Bhagat, Kristy L. Richards, Eric D. Hsi, William W.L. Choi, J. Han van Krieken, Qin Huang, Jooryung Huh, Weiyun Ai, Maurilio Ponzoni, Andrés J.M. Ferreri, Xiaoying Zhao, Jane N. Winter, Mingzhi Zhang, Ling Li, Michael B. Møller, Miguel A. Piris, Yong Li, Ronald S. Go, Lin Wu, L. Jeffrey Medeiros and Ken H. Young

Key points

  • CD30 expression defines a novel and unique subgroup of DLBCL with favorable clinical outcome and distinct gene expression signature


CD30, originally identified as a cell-surface marker of Reed-Sternberg and Hodgkin cells of classical Hodgkin lymphoma, is also expressed by several types of non-Hodgkin lymphoma, including a subset of diffuse large B-cell lymphoma (DLBCL). However, the prognostic and biological importance of CD30 expression in DLBCL is unknown. Here we report that CD30 expression is a favorable prognostic factor in a cohort of 903 de novo DLBCL patients. CD30 was expressed in approximately 14% of DLBCL patients. Patients with CD30+ DLBCL had superior 5-year overall survival (CD30+ 79% vs CD30- 59%, P=.001) and progression-free survival (P=.003). The favorable outcome of CD30 expression was maintained in both the germinal center B-cell and activated B-cell subtypes. Gene-expression profiling revealed the up-regulation of genes encoding negative regulators of NF-kB activation and lymphocyte survival, and down-regulation of those involving B-cell receptor signaling and B-cell proliferation, as well as prominent cytokine and stromal signatures in CD30+ DLBCL patients, suggesting a distinct molecular basis for its favorable outcome. Given the superior prognostic value, unique gene-expression signature and significant value of CD30 as a therapeutic target for Brentuximab vedotin in ongoing successful clinical trials, it would be appropriate to consider CD30+ DLBCL as a distinct subgroup of DLBCL.

  • Submitted October 17, 2012.
  • Accepted January 11, 2013.