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

Zijun Y. Xu-Monette, Shanxiang Zhang, Xin Li, Ganiraju C. Manyam, Xiao xiao Wang, Yi Xia, Carlo Visco, Alexandar Tzankov, 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, Han J. Van Krieken, Jooryung HuhMaurilio Ponzoni, Andrés J.M. Ferreri, Xiaoying Zhao, Michael B. Møller, Ben M. Parsons, Jane N. Winter, Miguel A. Piris, Jeffrey L. Medeiros, Ken H. Young

Research output: Contribution to journalArticle

11 Citations (Scopus)

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, p16 INK4A , 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 widetype 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 ΔNp63 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.

Original languageEnglish (US)
Pages (from-to)345-365
Number of pages21
JournalAging
Volume8
Issue number2
DOIs
StatePublished - Jan 1 2016
Externally publishedYes

Fingerprint

Lymphoma, Large B-Cell, Diffuse
Survival
Neoplasms
B-Lymphocytes
Cyclin-Dependent Kinase Inhibitor p16
Germinal Center
Gene Expression Profiling
Protein Isoforms
Carcinogenesis
Immunohistochemistry
Monoclonal Antibodies
Mutation
Research

Keywords

  • DLBCL
  • MDM2
  • P53
  • p63
  • TP53 mutation

ASJC Scopus subject areas

  • Aging
  • Cell Biology

Cite this

p63 expression confers significantly better survival outcomes in highrisk diffuse large B-cell lymphoma and demonstrates p53-like and p53-independent tumor suppressor function. / Xu-Monette, Zijun Y.; Zhang, Shanxiang; Li, Xin; Manyam, Ganiraju C.; Wang, Xiao xiao; Xia, Yi; Visco, Carlo; Tzankov, Alexandar; Zhang, Li; Montes-Moreno, Santiago; Dybkaer, Karen; Chiu, April; Orazi, Attilio; Zu, Youli; Bhagat, Govind; Richards, Kristy L.; Hsi, Eric D.; Choi, William W.L.; Van Krieken, Han J.; Huh, Jooryung; Ponzoni, Maurilio; Ferreri, Andrés J.M.; Zhao, Xiaoying; Møller, Michael B.; Parsons, Ben M.; Winter, Jane N.; Piris, Miguel A.; Medeiros, Jeffrey L.; Young, Ken H.

In: Aging, Vol. 8, No. 2, 01.01.2016, p. 345-365.

Research output: Contribution to journalArticle

Xu-Monette, ZY, Zhang, S, Li, X, Manyam, GC, Wang, XX, Xia, Y, Visco, C, Tzankov, A, Zhang, L, Montes-Moreno, S, Dybkaer, K, Chiu, A, Orazi, A, Zu, Y, Bhagat, G, Richards, KL, Hsi, ED, Choi, WWL, Van Krieken, HJ, Huh, J, Ponzoni, M, Ferreri, AJM, Zhao, X, Møller, MB, Parsons, BM, Winter, JN, Piris, MA, Medeiros, JL & Young, KH 2016, 'p63 expression confers significantly better survival outcomes in highrisk diffuse large B-cell lymphoma and demonstrates p53-like and p53-independent tumor suppressor function', Aging, vol. 8, no. 2, pp. 345-365. https://doi.org/10.18632/aging.100898
Xu-Monette, Zijun Y. ; Zhang, Shanxiang ; Li, Xin ; Manyam, Ganiraju C. ; Wang, Xiao xiao ; Xia, Yi ; Visco, Carlo ; Tzankov, Alexandar ; Zhang, Li ; Montes-Moreno, Santiago ; Dybkaer, Karen ; Chiu, April ; Orazi, Attilio ; Zu, Youli ; Bhagat, Govind ; Richards, Kristy L. ; Hsi, Eric D. ; Choi, William W.L. ; Van Krieken, Han J. ; Huh, Jooryung ; Ponzoni, Maurilio ; Ferreri, Andrés J.M. ; Zhao, Xiaoying ; Møller, Michael B. ; Parsons, Ben M. ; Winter, Jane N. ; Piris, Miguel A. ; Medeiros, Jeffrey L. ; Young, Ken H. / p63 expression confers significantly better survival outcomes in highrisk diffuse large B-cell lymphoma and demonstrates p53-like and p53-independent tumor suppressor function. In: Aging. 2016 ; Vol. 8, No. 2. pp. 345-365.
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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, p16 INK4A , 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 widetype 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 ΔNp63 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.",
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T1 - p63 expression confers significantly better survival outcomes in highrisk diffuse large B-cell lymphoma and demonstrates p53-like and p53-independent tumor suppressor function

AU - Xu-Monette, Zijun Y.

AU - Zhang, Shanxiang

AU - Li, Xin

AU - Manyam, Ganiraju C.

AU - Wang, Xiao xiao

AU - Xia, Yi

AU - Visco, Carlo

AU - Tzankov, Alexandar

AU - Zhang, Li

AU - Montes-Moreno, Santiago

AU - Dybkaer, Karen

AU - Chiu, April

AU - Orazi, Attilio

AU - Zu, Youli

AU - Bhagat, Govind

AU - Richards, Kristy L.

AU - Hsi, Eric D.

AU - Choi, William W.L.

AU - Van Krieken, Han J.

AU - Huh, Jooryung

AU - Ponzoni, Maurilio

AU - Ferreri, Andrés J.M.

AU - Zhao, Xiaoying

AU - Møller, Michael B.

AU - Parsons, Ben M.

AU - Winter, Jane N.

AU - Piris, Miguel A.

AU - Medeiros, Jeffrey L.

AU - Young, Ken H.

PY - 2016/1/1

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N2 - 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, p16 INK4A , 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 widetype 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 ΔNp63 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.

AB - 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, p16 INK4A , 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 widetype 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 ΔNp63 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.

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