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
- 1 Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- 2 University of Indiana School of Medicine, Indianapolis, IN 46202, USA
- 3 Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- 4 San Bortolo Hospital, Vicenza, Italy
- 5 University Hospital, Basel, Switzerland
- 6 Hospital Universitario Marques de Valdecilla, Santander, Spain
- 7 Aalborg University Hospital, Aalborg, Denmark
- 8 Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA
- 9 Weill Medical College of Cornell University, New York, NY 10065, USA
- 10 The Methodist Hospital, Houston, TX 77030, USA
- 11 Columbia University Medical Center and New York Presbyterian Hospital, New York, NY 10032, USA
- 12 University of North Carolina School of Medicine, Chapel Hill, NC 27513, USA
- 13 Cleveland Clinic, Cleveland, OH 44195, USA
- 14 University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong, China
- 15 Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands
- 16 Asan Medical Center, Ulsan University College of Medicine, Seoul, Korea
- 17 San Raffaele H. Scientific Institute, Milan, Italy
- 18 Zhejiang University School of Medicine, Zhejiang, China
- 19 Odense University Hospital, Odense, Denmark
- 20 Gundersen Medical Foundation, La Crosse, WI 54601, USA
- 21 Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
- 22 The University of Texas School of Medicine, Graduate School of Biomedical Sciences, Houston, TX 77030, USA
Received: January 15, 2016 Accepted: January 26, 2016 Published: February 14, 2016
https://doi.org/10.18632/aging.100898How to Cite
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.