Blood Journal
Leading the way in experimental and clinical research in hematology

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

  1. Shimin Hu1,
  2. Zijun Y. Xu-Monette1,
  3. Aarthi Balasubramanyam2,
  4. Ganiraju C. Manyam3,
  5. Carlo Visco4,
  6. Alexander Tzankov5,
  7. Wei-min Liu2,
  8. Roberto N. Miranda1,
  9. Li Zhang3,
  10. Santiago Montes-Moreno6,
  11. Karen Dybkaer7,
  12. April Chiu8,
  13. Attilio Orazi9,
  14. Youli Zu10,
  15. Govind Bhagat11,
  16. Kristy L. Richards12,
  17. Eric D. Hsi13,
  18. William W.L. Choi14,
  19. J. Han van Krieken15,
  20. Qin Huang16,
  21. Jooryung Huh17,
  22. Weiyun Ai18,
  23. Maurilio Ponzoni19,
  24. Andrés J.M. Ferreri19,
  25. Xiaoying Zhao20,
  26. Jane N. Winter21,
  27. Mingzhi Zhang22,
  28. Ling Li22,
  29. Michael B. Møller23,
  30. Miguel A. Piris6,
  31. Yong Li24,
  32. Ronald S. Go25,
  33. Lin Wu2,
  34. L. Jeffrey Medeiros1, and
  35. Ken H. Young1,*
  1. 1 Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States;
  2. 2 Roche Molecular Systems, Inc., Pleasanton, CA, United States;
  3. 3 Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States;
  4. 4 San Bortolo Hospital, Vicenza, Italy;
  5. 5 University Hospital, Basel, Switzerland;
  6. 6 Hospital Universitario Marques de Valdecilla, Santander, Spain;
  7. 7 Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark;
  8. 8 Memorial Sloan-Kettering Cancer Center, New York, NY, United States;
  9. 9 Weill Medical College of Cornell University, New York, NY, United States;
  10. 10 The Methodist Hospital, Houston, TX, United States;
  11. 11 Columbia University Medical Center and New York Presbyterian Hospital, New York, NY, United States;
  12. 12 University of North Carolina School of Medicine, Chapel Hill, NC, United States;
  13. 13 Cleveland Clinic, Cleveland, OH, United States;
  14. 14 University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong, China;
  15. 15 Radboud University Nijmegen Medical Center, Nijmegen, Netherlands;
  16. 16 City of Hope National Medical Center, Duarte, CA, United States;
  17. 17 San Medical Center, Ulsan University College of Medicine, Seoul, Korea, Republic of;
  18. 18 University of California San Francisco School of Medicine, San Francisco, CA, United States;
  19. 19 San Raffaele H. Scientific Institute, Milan, Italy;
  20. 20 Zhejiang University School of Medicine, Second University Hospital, Hangzhou, China;
  21. 21 Feinberg School of Medicine, Northwestern University, Chicago, IL, United States;
  22. 22 Zhengzhou University Medical Center, Zhengzhou, China;
  23. 23 Odense University Hospital, Odense, Denmark;
  24. 24 University of Louisville, Louisville, KY, United States;
  25. 25 Gundersen Lutheran Health System, La Crosse, WI, United States
  1. * Corresponding author; email: khyoung{at}mdanderson.org

Key points

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

Abstract

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.