title: 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.
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.
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Zijun Y
authors.initials: ZY
authors.lastname: Xu-Monette
authors.affiliation: University of Indiana School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Shanxiang
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Ganiraju C
authors.initials: GC
authors.lastname: Manyam
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Xiao-Xiao
authors.initials: XX
authors.lastname: Wang
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Xia
authors.affiliation: San Bortolo Hospital, Vicenza, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Visco
authors.affiliation: University Hospital, Basel, Switzerland.
authors.forename: Alexandar
authors.initials: A
authors.lastname: Tzankov
authors.affiliation: Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Hospital Universitario Marques de Valdecilla, Santander, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Montes-Moreno
authors.affiliation: Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Karen
authors.initials: K
authors.lastname: Dybkaer
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: April
authors.initials: A
authors.lastname: Chiu
authors.affiliation: Weill Medical College of Cornell University, New York, NY 10065, USA.
authors.forename: Attilio
authors.initials: A
authors.lastname: Orazi
authors.affiliation: The Methodist Hospital, Houston, TX 77030, USA.
authors.forename: Youli
authors.initials: Y
authors.lastname: Zu
authors.affiliation: Columbia University Medical Center and New York Presbyterian Hospital, New York, NY 10032, USA.
authors.forename: Govind
authors.initials: G
authors.lastname: Bhagat
authors.affiliation: University of North Carolina School of Medicine, Chapel Hill, NC 27513, USA.
authors.forename: Kristy L
authors.initials: KL
authors.lastname: Richards
authors.affiliation: Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Eric D
authors.initials: ED
authors.lastname: Hsi
authors.affiliation: University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong, China.
authors.forename: William W L
authors.initials: WW
authors.lastname: Choi
authors.affiliation: Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands.
authors.forename: J Han
authors.initials: JH
authors.lastname: van Krieken
authors.affiliation: Asan Medical Center, Ulsan University College of Medicine, Seoul, Korea.
authors.forename: Jooryung
authors.initials: J
authors.lastname: Huh
authors.affiliation: San Raffaele H. Scientific Institute, Milan, Italy.
authors.forename: Maurilio
authors.initials: M
authors.lastname: Ponzoni
authors.affiliation: San Raffaele H. Scientific Institute, Milan, Italy.
authors.forename: Andrés J M
authors.initials: AJ
authors.lastname: Ferreri
authors.affiliation: Zhejiang University School of Medicine, Zhejiang, China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Odense University Hospital, Odense, Denmark.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Møller
authors.affiliation: Gundersen Medical Foundation, La Crosse, WI 54601, USA.
authors.forename: Ben M
authors.initials: BM
authors.lastname: Parsons
authors.affiliation: Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
authors.forename: Jane N
authors.initials: JN
authors.lastname: Winter
authors.affiliation: Hospital Universitario Marques de Valdecilla, Santander, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Piris
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: L Jeffrey
authors.initials: LJ
authors.lastname: Medeiros
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.|The University of Texas School of Medicine, Graduate School of Biomedical Sciences, Houston, TX 77030, USA.
authors.forename: Ken H
authors.initials: KH
authors.lastname: Young
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000032:analysis / Q000378:metabolism*; D059467:Transcriptome; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C495901:TP53 protein, human; C115051:TP63 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins
keywords: DLBCL; MDM2; TP53 mutation; p53; p63