Skip to main content
Top
Published in: Diagnostic Pathology 1/2019

Open Access 01-12-2019 | Lymphoma | Research

Expression of P63 and its correlation with prognosis in diffuse large B-cell lymphoma: a single center experience

Authors: Wan-Ming Hu, Jie-Tian Jin, Chen-Yan Wu, Jia-Bin Lu, Li-Hong Zhang, Jing Zeng, Su-Xia Lin

Published in: Diagnostic Pathology | Issue 1/2019

Login to get access

Abstract

Background

Large B cell lymphoma (DLBCL) is the most common type of non-Hodgkin’s lymphoma among adults. In some cases, DLBCL may seem similar to carcinoma cells, presenting a round, oval, or polygonal shape and clear nuclei. We found that the expression of P63 accounted for a considerable proportion of DLBCL cases. Under the circumstances, P63 expression may lead to a misdiagnosis, especially with a small biopsy. We aim to investigate the expression status and prognostic significance of P63 in a cohort of Chinese DLBCL patients.

Methods

P63, ΔNP63(P40), P53 and Ki67 were detected by immunohistochemistry (IHC). A ROC curve was adopted to find the best cut-off value for positive P63/P53 expression and high Ki67 expression. We defined P53 as positive when ≥50% of the tumor cells showed staining. The relationship between P63 and P53/Ki67 expression was examined. Time-to-event endpoints were estimated according to the Kaplan-Meier method. Moreover, multivariate analyses were conducted to evaluate the prognostic factors in DLBCL.

Results

Out of all the 159 DLBCL cases, 76 (47.8%) expressed P63 in the nuclei, while 41 (25.8%) were determined to have high expression by using a ROC cut-off value “≥6”. Examination of the different P63 isoforms revealed that the ΔNP63(P40) was unclearly and weakly expressed in only 3 cases, showing a fuzzy yellow cytoplasm. P63 expression was not correlated with subtype (GCB or non-GCB) or P53 but was correlated with a high proliferative index (Ki67). Kaplan-Meier analyses revealed that P63 expression was correlated with overall survival, and P63 positive cases showed poor survival outcomes (P<0.05) in our cohort.

Conclusions

ΔNP63(P40) is a useful marker in the differential diagnosis of poorly differentiated squamous cell carcinoma versus DLBCL in small needle biopsy. P63 may be involved in DLBCL tumor progression, and it is an unfavorable prognostic marker in DLBCL. A subgroup of P63 and P53 coexpression DLBCL patients with an extremely poor prognosis should be noted.
Literature
1.
go back to reference Su X, Chakravarti D, Flores ER. p63 steps into the limelight: crucial roles in the suppression of tumorigenesis and metastasis. Nat Rev Cancer. 2013;13(2):136–43.CrossRef Su X, Chakravarti D, Flores ER. p63 steps into the limelight: crucial roles in the suppression of tumorigenesis and metastasis. Nat Rev Cancer. 2013;13(2):136–43.CrossRef
2.
go back to reference Di Como CJ, Urist MJ, Babayan I, Drobnjak M, Hedvat CV, Teruya-Feldstein J, Pohar K, Hoos A, Cordon-Cardo C. p63 expression profiles in human normal and tumor tissues. Clin Cancer Res. 2002;8(2):494–501.PubMed Di Como CJ, Urist MJ, Babayan I, Drobnjak M, Hedvat CV, Teruya-Feldstein J, Pohar K, Hoos A, Cordon-Cardo C. p63 expression profiles in human normal and tumor tissues. Clin Cancer Res. 2002;8(2):494–501.PubMed
3.
go back to reference Nylander K, Vojtesek B, Nenutil R, Lindgren B, Roos G, Zhanxiang W, Sjostrom B, Dahlqvist A, Coates PJ. Differential expression of p63 isoforms in normal tissues and neoplastic cells. J Pathol. 2002;198(4):417–27.CrossRef Nylander K, Vojtesek B, Nenutil R, Lindgren B, Roos G, Zhanxiang W, Sjostrom B, Dahlqvist A, Coates PJ. Differential expression of p63 isoforms in normal tissues and neoplastic cells. J Pathol. 2002;198(4):417–27.CrossRef
4.
go back to reference Sethi I, Romano RA, Gluck C, Smalley K, Vojtesek B, Buck MJ, Sinha S. A global analysis of the complex landscape of isoforms and regulatory networks of p63 in human cells and tissues. BMC Genomics. 2015;16:584.CrossRef Sethi I, Romano RA, Gluck C, Smalley K, Vojtesek B, Buck MJ, Sinha S. A global analysis of the complex landscape of isoforms and regulatory networks of p63 in human cells and tissues. BMC Genomics. 2015;16:584.CrossRef
5.
go back to reference Hibi K, Trink B, Patturajan M, Westra WH, Caballero OL, Hill DE, Ratovitski EA, Jen J, Sidransky D. AIS is an oncogene amplified in squamous cell carcinoma. Proc Natl Acad Sci U S A. 2000;97(10):5462–7.CrossRef Hibi K, Trink B, Patturajan M, Westra WH, Caballero OL, Hill DE, Ratovitski EA, Jen J, Sidransky D. AIS is an oncogene amplified in squamous cell carcinoma. Proc Natl Acad Sci U S A. 2000;97(10):5462–7.CrossRef
6.
go back to reference Fukushima N, Satoh T, Sueoka N, Sato A, Ide M, Hisatomi T, Kuwahara N, Tomimasu R, Tsuneyoshi N, Funai N, et al. Clinico-pathological characteristics of p63 expression in B-cell lymphoma. Cancer Sci. 2006;97(10):1050–5.CrossRef Fukushima N, Satoh T, Sueoka N, Sato A, Ide M, Hisatomi T, Kuwahara N, Tomimasu R, Tsuneyoshi N, Funai N, et al. Clinico-pathological characteristics of p63 expression in B-cell lymphoma. Cancer Sci. 2006;97(10):1050–5.CrossRef
7.
go back to reference Hedvat CV, Teruya-Feldstein J, Puig P, Capodieci P, Dudas M, Pica N, Qin J, Cordon-Cardo C, Di Como CJ. Expression of p63 in diffuse large B-cell lymphoma. Appl Immunohistochem Mol Morphol. 2005;13(3):237–42.CrossRef Hedvat CV, Teruya-Feldstein J, Puig P, Capodieci P, Dudas M, Pica N, Qin J, Cordon-Cardo C, Di Como CJ. Expression of p63 in diffuse large B-cell lymphoma. Appl Immunohistochem Mol Morphol. 2005;13(3):237–42.CrossRef
8.
go back to reference Hu W, Yang Y, Xi S, Sai K, Su D, Zhang X, Lin S, Zeng J. Expression of CPEB4 in human glioma and its correlations with prognosis. Medicine (Baltimore). 2015;94(27):e979.CrossRef Hu W, Yang Y, Xi S, Sai K, Su D, Zhang X, Lin S, Zeng J. Expression of CPEB4 in human glioma and its correlations with prognosis. Medicine (Baltimore). 2015;94(27):e979.CrossRef
9.
go back to reference Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017;45(W1):W98–W102.CrossRef Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017;45(W1):W98–W102.CrossRef
10.
go back to reference Kucukzeybek BB, Bener S, Calli AO, Paksoy TD, Payzin B. Prognostic significance of Bcl-2 and p53 protein expressions and Ki67 proliferative index in diffuse large B-cell lymphoma. Turk J Haematol. 2013;30(3):275–82.CrossRef Kucukzeybek BB, Bener S, Calli AO, Paksoy TD, Payzin B. Prognostic significance of Bcl-2 and p53 protein expressions and Ki67 proliferative index in diffuse large B-cell lymphoma. Turk J Haematol. 2013;30(3):275–82.CrossRef
11.
go back to reference O'Malley DP, Dogan A, Fedoriw Y, Medeiros LJ, Ok CY, Salama ME. American registry of pathology expert opinions: immunohistochemical evaluation of classic Hodgkin lymphoma. Ann Diagn Pathol. 2019;39:105–10.CrossRef O'Malley DP, Dogan A, Fedoriw Y, Medeiros LJ, Ok CY, Salama ME. American registry of pathology expert opinions: immunohistochemical evaluation of classic Hodgkin lymphoma. Ann Diagn Pathol. 2019;39:105–10.CrossRef
12.
go back to reference Zamo A, Malpeli G, Scarpa A, Doglioni C, Chilosi M, Menestrina F. Expression of TP73L is a helpful diagnostic marker of primary mediastinal large B-cell lymphomas. Mod Pathol. 2005;18(11):1448–53.CrossRef Zamo A, Malpeli G, Scarpa A, Doglioni C, Chilosi M, Menestrina F. Expression of TP73L is a helpful diagnostic marker of primary mediastinal large B-cell lymphomas. Mod Pathol. 2005;18(11):1448–53.CrossRef
13.
go back to reference Shi QY, Feng X, Chen H, Ma HH, Lu ZF, Shi QL, Zhou XJ, Shen Q. Primary mediastinal large B-cell lymphoma: a clinicopathologic study of 27 cases. Zhonghua Bing Li Xue Za Zhi. 2017;46(9):607–12.PubMed Shi QY, Feng X, Chen H, Ma HH, Lu ZF, Shi QL, Zhou XJ, Shen Q. Primary mediastinal large B-cell lymphoma: a clinicopathologic study of 27 cases. Zhonghua Bing Li Xue Za Zhi. 2017;46(9):607–12.PubMed
14.
go back to reference Robson A, Shukur Z, Ally M, Kluk J, Liu K, Pincus L, Sahni D, Sundram U, Subtil A, Karai L, et al. Immunocytochemical p63 expression discriminates between primary cutaneous follicle centre cell and diffuse large B cell lymphoma-leg type, and is of the TAp63 isoform. Histopathology. 2016;69(1):11–9.CrossRef Robson A, Shukur Z, Ally M, Kluk J, Liu K, Pincus L, Sahni D, Sundram U, Subtil A, Karai L, et al. Immunocytochemical p63 expression discriminates between primary cutaneous follicle centre cell and diffuse large B cell lymphoma-leg type, and is of the TAp63 isoform. Histopathology. 2016;69(1):11–9.CrossRef
15.
go back to reference Park CK, Oh YH. Expression of p63 in reactive hyperplasias and malignant lymphomas. J Korean Med Sci. 2005;20(5):752–8.CrossRef Park CK, Oh YH. Expression of p63 in reactive hyperplasias and malignant lymphomas. J Korean Med Sci. 2005;20(5):752–8.CrossRef
16.
go back to reference Hallack NA, Siqueira SA, Dulley FL, Ruiz MA, Chamone DA, Pereira J. p63 protein expression in high risk diffuse large B-cell lymphoma. J Clin Pathol. 2009;62(1):77–9.CrossRef Hallack NA, Siqueira SA, Dulley FL, Ruiz MA, Chamone DA, Pereira J. p63 protein expression in high risk diffuse large B-cell lymphoma. J Clin Pathol. 2009;62(1):77–9.CrossRef
17.
go back to reference Xu-Monette ZY, Zhang S, Li X, Manyam GC, Wang XX, Xia Y, Visco C, Tzankov A, Zhang L, Montes-Moreno S, et al. 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. Aging (Albany NY). 2016;8(2):345–65.CrossRef Xu-Monette ZY, Zhang S, Li X, Manyam GC, Wang XX, Xia Y, Visco C, Tzankov A, Zhang L, Montes-Moreno S, et al. 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. Aging (Albany NY). 2016;8(2):345–65.CrossRef
18.
go back to reference Massion PP, Taflan PM, Jamshedur RS, Yildiz P, Shyr Y, Edgerton ME, Westfall MD, Roberts JR, Pietenpol JA, Carbone DP, et al. Significance of p63 amplification and overexpression in lung cancer development and prognosis. Cancer Res. 2003;63(21):7113–21.PubMed Massion PP, Taflan PM, Jamshedur RS, Yildiz P, Shyr Y, Edgerton ME, Westfall MD, Roberts JR, Pietenpol JA, Carbone DP, et al. Significance of p63 amplification and overexpression in lung cancer development and prognosis. Cancer Res. 2003;63(21):7113–21.PubMed
19.
go back to reference Miller TP, Grogan TM, Dahlberg S, Spier CM, Braziel RM, Banks PM, Foucar K, Kjeldsberg CR, Levy N, Nathwani BN, et al. Prognostic significance of the Ki-67-associated proliferative antigen in aggressive non-Hodgkin's lymphomas: a prospective southwest oncology group trial. Blood. 1994;83(6):1460–6.CrossRef Miller TP, Grogan TM, Dahlberg S, Spier CM, Braziel RM, Banks PM, Foucar K, Kjeldsberg CR, Levy N, Nathwani BN, et al. Prognostic significance of the Ki-67-associated proliferative antigen in aggressive non-Hodgkin's lymphomas: a prospective southwest oncology group trial. Blood. 1994;83(6):1460–6.CrossRef
20.
go back to reference Xie Y, Bulbul MA, Ji L, Inouye CM, Groshen SG, Tulpule A, O'Malley DP, Wang E, Siddiqi IN. p53 expression is a strong marker of inferior survival in de novo diffuse large B-cell lymphoma and may have enhanced negative effect with MYC coexpression: a single institutional clinicopathologic study. Am J Clin Pathol. 2014;141(4):593–604.CrossRef Xie Y, Bulbul MA, Ji L, Inouye CM, Groshen SG, Tulpule A, O'Malley DP, Wang E, Siddiqi IN. p53 expression is a strong marker of inferior survival in de novo diffuse large B-cell lymphoma and may have enhanced negative effect with MYC coexpression: a single institutional clinicopathologic study. Am J Clin Pathol. 2014;141(4):593–604.CrossRef
21.
go back to reference Wang XJ, Medeiros LJ, Bueso-Ramos CE, Tang G, Wang S, Oki Y, Desai P, Khoury JD, Miranda RN, Tang Z, et al. P53 expression correlates with poorer survival and augments the negative prognostic effect of MYC rearrangement, expression or concurrent MYC/BCL2 expression in diffuse large B-cell lymphoma. Mod Pathol. 2017;30(2):194–203.CrossRef Wang XJ, Medeiros LJ, Bueso-Ramos CE, Tang G, Wang S, Oki Y, Desai P, Khoury JD, Miranda RN, Tang Z, et al. P53 expression correlates with poorer survival and augments the negative prognostic effect of MYC rearrangement, expression or concurrent MYC/BCL2 expression in diffuse large B-cell lymphoma. Mod Pathol. 2017;30(2):194–203.CrossRef
22.
go back to reference Clipson A, Barrans S, Zeng N, Crouch S, Grigoropoulos NF, Liu H, Kocialkowski S, Wang M, Huang Y, Worrillow L, et al. The prognosis of MYC translocation positive diffuse large B-cell lymphoma depends on the second hit. J Pathol Clin Res. 2015;1(3):125–33.CrossRef Clipson A, Barrans S, Zeng N, Crouch S, Grigoropoulos NF, Liu H, Kocialkowski S, Wang M, Huang Y, Worrillow L, et al. The prognosis of MYC translocation positive diffuse large B-cell lymphoma depends on the second hit. J Pathol Clin Res. 2015;1(3):125–33.CrossRef
23.
go back to reference Xu-Monette ZY, Wu L, Visco C, Tai YC, Tzankov A, Liu WM, Montes-Moreno S, Dybkaer K, Chiu A, Orazi A, et al. Mutational profile and prognostic significance of TP53 in diffuse large B-cell lymphoma patients treated with R-CHOP: report from an international DLBCL rituximab-CHOP consortium program study. Blood. 2012;120(19):3986–96.CrossRef Xu-Monette ZY, Wu L, Visco C, Tai YC, Tzankov A, Liu WM, Montes-Moreno S, Dybkaer K, Chiu A, Orazi A, et al. Mutational profile and prognostic significance of TP53 in diffuse large B-cell lymphoma patients treated with R-CHOP: report from an international DLBCL rituximab-CHOP consortium program study. Blood. 2012;120(19):3986–96.CrossRef
24.
go back to reference Xu-Monette ZY, Moller MB, Tzankov A, Montes-Moreno S, Hu W, Manyam GC, Kristensen L, Fan L, Visco C, Dybkaer K, et al. MDM2 phenotypic and genotypic profiling, respective to TP53 genetic status, in diffuse large B-cell lymphoma patients treated with rituximab-CHOP immunochemotherapy: a report from the international DLBCL rituximab-CHOP consortium program. Blood. 2013;122(15):2630–40.CrossRef Xu-Monette ZY, Moller MB, Tzankov A, Montes-Moreno S, Hu W, Manyam GC, Kristensen L, Fan L, Visco C, Dybkaer K, et al. MDM2 phenotypic and genotypic profiling, respective to TP53 genetic status, in diffuse large B-cell lymphoma patients treated with rituximab-CHOP immunochemotherapy: a report from the international DLBCL rituximab-CHOP consortium program. Blood. 2013;122(15):2630–40.CrossRef
Metadata
Title
Expression of P63 and its correlation with prognosis in diffuse large B-cell lymphoma: a single center experience
Authors
Wan-Ming Hu
Jie-Tian Jin
Chen-Yan Wu
Jia-Bin Lu
Li-Hong Zhang
Jing Zeng
Su-Xia Lin
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Diagnostic Pathology / Issue 1/2019
Electronic ISSN: 1746-1596
DOI
https://doi.org/10.1186/s13000-019-0880-7

Other articles of this Issue 1/2019

Diagnostic Pathology 1/2019 Go to the issue