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Research Paper|Volume 8, Issue 2|pp 345—365

p63 expression confers significantly better survival outcomes in high-risk diffuse large B-cell lymphoma and demonstrates p53-like and p53-independent tumor suppressor function

Zijun Y. Xu-Monette1, Shanxiang Zhang2, Xin Li1, Ganiraju C. Manyam3, Xiao-xiao Wang1, Yi Xia1, Carlo Visco4, Alexandar Tzankov5, Li Zhang3, Santiago Montes-Moreno6, Karen Dybkaer7, April Chiu8, Attilio Orazi9, Youli Zu10, Govind Bhagat11, Kristy L. Richards12, Eric D. Hsi13, William W.L. Choi14, J. Han van Krieken15, Jooryung Huh16, Maurilio Ponzoni17, Andrés J.M. Ferreri17, Xiaoying Zhao18, Michael B. Møller19, Ben M. Parsons20, Jane N. Winter21, Miguel A. Piris6, L. Jeffrey Medeiros1, Ken H. Young1,22
  • 1Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
  • 2University of Indiana School of Medicine, Indianapolis, IN 46202, USA
  • 3Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
  • 4San Bortolo Hospital, Vicenza, Italy
  • 5University Hospital, Basel, Switzerland
  • 6Hospital Universitario Marques de Valdecilla, Santander, Spain
  • 7Aalborg University Hospital, Aalborg, Denmark
  • 8Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA
  • 9Weill Medical College of Cornell University, New York, NY 10065, USA
  • 10The Methodist Hospital, Houston, TX 77030, USA
  • 11Columbia University Medical Center and New York Presbyterian Hospital, New York, NY 10032, USA
  • 12University of North Carolina School of Medicine, Chapel Hill, NC 27513, USA
  • 13Cleveland Clinic, Cleveland, OH 44195, USA
  • 14University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong, China
  • 15Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands
  • 16Asan Medical Center, Ulsan University College of Medicine, Seoul, Korea
  • 17San Raffaele H. Scientific Institute, Milan, Italy
  • 18Zhejiang University School of Medicine, Zhejiang, China
  • 19Odense University Hospital, Odense, Denmark
  • 20Gundersen Medical Foundation, La Crosse, WI 54601, USA
  • 21Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
  • 22The University of Texas School of Medicine, Graduate School of Biomedical Sciences, Houston, TX 77030, USA

* * Equal contribution

Received: January 15, 2016Accepted: January 26, 2016Published: February 14, 2016

Copyright: © 2016 Xu-Monette et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

The role of p53 family member, p63 in oncogenesis is the subject of controversy. Limited research has been done on the clinical implications of p63 expression in diffuse large B-cell lymphoma (DLBCL). In this study, we assessed p63 expression in de novo DLBCL samples (n=795) by immunohistochemistry with a pan-p63-monoclonal antibody and correlated it with other clinicopathologic factors and clinical outcomes. p63 expression was observed in 42.5% of DLBCL, did not correlate with p53 levels, but correlated with p21, MDM2, p16INK4A, Ki-67, Bcl-6, IRF4/MUM-1 and CD30 expression, REL gains, and BCL6 translocation. p63 was an independent favorable prognostic factor in DLBCL, which was most significant in patients with International Prognostic Index (IPI) >2, and in activated-B-cell–like DLBCL patients with wide-type TP53. The prognostic impact in germinal-center-B-cell–like DLBCL was not apparent, which was likely due to the association of p63 expression with high-risk IPI, and potential presence of ∆Np63 isoform in TP63 rearranged patients (a mere speculation). Gene expression profiling suggested that p63 has both overlapping and distinct functions compared with p53, and that p63 and mutated p53 antagonize each other. In summary, p63 has p53-like and p53-independent functions and favorable prognostic impact, however this protective effect can be abolished by TP53 mutations.