Association of p53 protein expression with the presence of a 17p13 locus deletion of the TP53 gene and with the survival of patients with diffuse large B-cell lymphoma

Cover Page


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Background. A significant role in the pathogenesis, resistance to treatment and progression of many types of lymphomas, including diffuse large B-cell lymphoma, is assigned to the TP53 gene. Literature data on the prognostic significance of the expression of its product, the p53 protein, and its association with aberrations at the 17p13 locus are ambiguous.

Aim. To assess the relationship of p53 protein expression with the presence of a 17p13 locus deletion of the TP53 gene and the survival of patients with diffuse large B-cell lymphoma.

Material and methods. The study included 75 patients with newly diagnosed diffuse large B-cell lymphoma who received R-CHOP therapy. The calculation of the relative content of tumor cells expressing p53 was carried out using immunohistochemical and morphometric methods on biopsy samples of lymph nodes. The 17p13/TP53 deletion was determined by fluorescent in situ hybridization. The threshold level of p53-positive tumor cells, corresponding to 43%, was calculated by ROC analysis. The association between p53 protein expression and the presence of a 17p13 deletion was assessed using Fisher's (F) and Pearson's χ2 tests. The correlation dependence was evaluated by the Cramer method (V). Five-year overall and progression-free survival was calculated using the Kaplan–Meier method. Differences between the indicators were considered statistically significant at p <0.05.

Results. The frequency of 17p13/TP53 deletion was higher in patients with high expression of p53 (≥43%) compared to the group of patients with low expression: 87.5 and 12.5%, respectively (p=0.018). A direct correlation between a high level of p53 expression (>43%) and the presence of a 17p13/TP53 deletion was found (p=0.018). Five-year overall and progression-free survival in patients with a proportion of p53-positive cells> 43% was significantly lower than in patients with its subthreshold value: 54.5 versus 81.0% (p=0.014) and 45.5 versus 66.7% (p=0.022), respectively.

Conclusion. High expression of the p53 protein is associated with the presence of a 17p13 locus deletion and a low five-year survival rate in patients with diffuse large B-cell lymphoma.

Keywords

Full Text

Restricted Access

About the authors

Mariia V. Sarpova

Kirov Research Institute of Hematology and Blood Transfusion of the Federal Medical and Biological Agency

Author for correspondence.
Email: marisarpova@mail.ru
ORCID iD: 0000-0001-5949-7865
SPIN-code: 8444-6740

Researcher, Laboratory of Pathomorphology

Russian Federation, Kirov, Russia

Elena V. Vaneeva

Kirov Research Institute of Hematology and Blood Transfusion of the Federal Medical and Biological Agency

Email: vaneeva@niigpk.ru
ORCID iD: 0000-0003-1045-2011
SPIN-code: 9663-3399
Scopus Author ID: 57222653084

Researcher, Laboratory of Pathomorphology

Russian Federation, Kirov, Russia

Dmitry A. Diakonov

Kirov Research Institute of Hematology and Blood Transfusion of the Federal Medical and Biological Agency

Email: dyakonov@niigpk.ru
ORCID iD: 0000-0001-8688-1344
SPIN-code: 6301-6557
Scopus Author ID: 55920048300

M.D., Cand. Sci. (Med.), Head, Laboratory of Pathomorphology

Russian Federation, Kirov, Russia

Vitaly A. Rosin

Kirov Research Institute of Hematology and Blood Transfusion of the Federal Medical and Biological Agency

Email: rosin@niigpk.ru
ORCID iD: 0000-0003-2054-2870
SPIN-code: 8058-3942
Scopus Author ID: 55893734700

M.D., Cand. Sci. (Med.), Senior Researcher, Laboratory of Pathomorphology

Russian Federation, Kirov, Russia

Svetlana V. Samarina

Kirov Research Institute of Hematology and Blood Transfusion of the Federal Medical and Biological Agency

Email: samarina@niigpk.ru
ORCID iD: 0000-0001-8639-719X

M.D., Head, Clinical Diagnostic Depart.

Russian Federation, Kirov, Russia

References

  1. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J. WHO classification of tumours of haematopoietic and lymphoid tissues. Revised 4th edition. Lyon: IARC; 2017. 585 p.
  2. Sehn LH, Gascoyne RD. Diffuse large B-cell lymphoma: optimizing outcome in the context of clinical and biologic heterogeneity. Blood. 2015;125(1):22–32. doi: 10.1182/blood-2014-05-577189.
  3. Wight JC, Chonga G, Grigga AP, Hawkesa EA. Prognostication of diffuse large B-cell lymphoma in the molecular era: Moving beyond the IPI. Blood. 2018;32(5):400–415. doi: 10.1016/j.blre.2018.03.005.
  4. Kaplanov KD, Volkov NP, Klitochenko TYu, Matveeva IV, Shipaeva AL, Shirokova MN, Davydova NV, Gemdzhian EG, Abramov DS, Konovalov DM, Snigur GL, Red’kina NA. Analysis results of the regional registry of patients with diffuse large B-cell lymphoma: risk factors and chemo-immunotherapy issues. Clinical oncohematology. 2019;12(2):154–164. (In Russ.) doi: 10.21320/2500-2139-2019-12-2-154-164.
  5. Coiffier B, Sarkozy C. Diffuse large B-cell lymphoma: R-CHOP failure — what to do? Hematology Am Soc Hematol Educ Program. 2016;2016(1):366–378. doi: 10.1182/asheducation-2016.1.366.
  6. Xu-Monette ZY, Wu L, Visco C, Tai YC, Tzankov A, Liu WM, Montes-Moreno S, Dybkaer K, Chiu A, Orazi A, Zu Y, Bhagat G, Richards KL, Hsi ED, Zhao XF, Choi WW, Zhao X, van Krieken JH, Huang Q, Huh J, Ai W, Ponzoni M, Ferreri AJ, Zhou F, Kahl BS, Winter JN, Xu W, Li J, Go RS, Li Y, Piris MA, Møller MB, Miranda RN, Abruzzo LV, Medeiros LJ, Young KH. 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):3986–3996. doi: 10.1182/blood-2012-05-433334.
  7. Berendsen MR, Stevens WBC, van den Brand M, van Krieken JH, Scheijen B. Molecular genetics of relapsed diffuse large B-cell lymphoma: Insight into mechanisms of therapy resistance. Cancers. 2020;12(12):3553. doi: 10.3390/cancers12123553.
  8. Donehower LA, Soussi T, Korkut A, Liu Y, Schultz A, Cardenas M, Li X, Babur O, Hsu TK, Lichtarge O, Weinstein JN, Akbani R, Wheeler DA. Integrated analysis of TP53 gene and pathway alterations in the Cancer Genome Atlas. Cell Rep. 2019;28(5):1370–1384.e5. doi: 10.1016/j.celrep.2019.07.001.
  9. Leveille E, Johnson NA. Genetic events inhibiting apoptosis in diffuse large B cell lymphoma. Cancers. 2021;13(9):2167. doi: 10.3390/cancers13092167.
  10. Zlamalikova L, Moulis M, Ravcukova B, Liskova K, Malcikova J, Salek D, Jarkovsky J, Svitakova M, Hrabalkova R, Smarda J, Smardova J. Complex analysis of the TP53 tumor suppressor in mantle cell and diffuse large B-cell lymphomas. Oncol Rep. 2017;4:2535–2542. doi: 10.3892/or.2017.5891.
  11. Wang XJ, Medeiros LJ, Bueso-Ramos C, Tang G, Wang S, Oki Y, Desai P, Khoury JD, Miranda RN, Tang Z, Reddy N, Li S. 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;30:194–203. doi: 10.1038/modpathol.2016.178.
  12. Xie Y, Bulbul MA, Ji L, Inouye C, Groshen S, Tulpule A, O’Malley D, Wang E, Siddiqi I. 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. doi: 10.1309/AJCPPHMZ6VHF0WQV.
  13. Peroja P, Pedersen M, Mantere T, Nørgaard P, Peltonen J, Haapasaari K-M, Böhm J, Jantunen E, Turpeenniemi-Hujanen T, Rapakko K, Karihtala P, Soini Y, Vasala K, Kuittinen O. Mutation of TP53, translocation analysis and immunohistochemical expression of MYC, BCL-2 and BCL-6 in patients with DLBCL treated with R-CHOP. Sci Rep. 2018;8:14814. doi: 10.1038/s41598-018-33230-3.
  14. Joerger A, Fersht A. Structure-function-rescue: the diverse nature of common p53 cancer mutants. Oncogene. 2007;26:2226–2242. doi: 10.1038/sj.onc.1210291.
  15. Cao Y, Zhu T, Zhang P, Xiao M, Yi S, Yang Y, Li Q, Ling S, Wang Y, Gao L, Zhu L, Wang J, Wang N, Huang L, Zhang P, Zhai Q, Qiu L, Zhou J. Mutations or copy number losses of CD58 and TP53 genes in diffuse large B cell lymphoma are independent unfavorable prognostic factors. Oncotarget. 2016;7(50):83294–83307. doi: 10.18632/oncotarget.13065.
  16. Vaneeva EV, Rosin VA, Dyakonov DA, Luchinin AS, Kochetov NL, Samarina SV. Significance of pAKT1 expression in diffuse large B-cell lymphoma. Bulletin of Siberian Medicine. 2021;(3):6–13. (In Russ.) doi: 10.20538/1682-0363-2021-3-13-20.
  17. Vaneeva EV, Rosin VA, Dyakonov DA, Samarina SV, Rylov AV. Prognostic value of pSTAT3 expression in diffusive B-large cell lymphoma in the Russian patient sample. Siberian Scientific Medical Journal. 2019;39(5):125–133. (In Russ.) doi: 10.15372/SMMJ20190515.

Supplementary files

Supplementary Files
Action
1. JATS XML
2. Рис. 1. Лимфатический узел. Иммуногистохимическая окраска опухолевых клеток антителом к p53: высокая (а) и низкая (б) экспрессия, ×1000

Download (45KB)
3. Рис. 2. Общая (а) и беспрогрессивная (б) выживаемость больных диффузной В-крупноклеточной лимфомой с высокой (нижняя линия, n=33) и низкой (верхняя линия, n=42) экспрессией p53 опухолевыми клетками

Download (31KB)
4. Рис. 3. Общая (а) и беспрогрессивная (б) выживаемость больных диффузной В-крупноклеточной лимфомой с делецией ТР53/17р13 (нижняя линия, n=8) и без данной аберрации (верхняя линия, n=67)

Download (30KB)

© 2023 Eco-Vector





This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies