The Profile of P63 Expression and Epstein-Barr-Encoded RNA (EBER) Distribution in Primary Central Nervous System Lymphoma: A Retrospective Bi-Center Study

Authors

  • Erna Kristiani Department of Anatomical Pathology, Faculty of Medicine, University of Pelita Harapan, Jendral Sudirman Boulevard, Lippo Karawaci, Tangerang, Indonesia 15811
  • Stephanie Marisca Department of Anatomical Pathology, Faculty of Medicine, University of Pelita Harapan, Jendral Sudirman Boulevard, Lippo Karawaci, Tangerang, Indonesia 15811
  • Sally Suharyani Department of Medicine, Faculty of Medicine, University of Pelita Harapan, Jendral Sudirman Boulevard, Lippo Karawaci, Tangerang, Indonesia 15811
  • Kevin Dermawan Department of Medicine, Faculty of Medicine, University of Pelita Harapan, Jendral Sudirman Boulevard, Lippo Karawaci, Tangerang, Indonesia 15811
  • Stephanie T. Widodo Department of Medicine, Faculty of Medicine, University of Pelita Harapan, Jendral Sudirman Boulevard, Lippo Karawaci, Tangerang, Indonesia 15811
  • Maria F. Ham Department of Anatomical Pathology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
  • Agnes S. Harahap Department of Anatomical Pathology, Faculty of Medicine, University of Pelita Harapan, Jendral Sudirman Boulevard, Lippo Karawaci, Tangerang, Indonesia 15811
  • Eka Susanto Department of Anatomical Pathology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
  • Hartono Tjahjadi Department of Anatomical Pathology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
  • Julius July Department of Neurosurgery, Faculty of Medicine, University of Pelita Harapan, Jendral Sudirman Boulevard, Lippo Karawaci, Tangerang, Indonesia 15811

DOI:

https://doi.org/10.19166/med.v14i2.9545

Keywords:

Primary central nervous system lymphoma (PCNSL), P63 expression, Epstein-Barr-Encoded RNA (EBER), Epstein-Barr virus (EBV), TP63 mutation

Abstract

Background : Primary central nervous system lymphoma (PCNSL) is a type of lymphoma occurring around 0.5 – 1.2% of all intracranial neoplasms. However, recent epidemiological research shows a threefold increase in the number of cases. The Epstein-Barr virus (EBV) and PCNSL are both associated with the condition of immunosuppression or immunodeficiency, which often found to have a significant relationship with each other. Moreover, the TP63 mutation is associated with a poor prognosis.

Methods : This is a descriptive study to assess the expression of TP63 and EBER on PCNSL, and present the characteristics of the disease. The study was conducted on 25 cases from two health centers with the most cases of brain tumors in Indonesia, Siloam Hospital Lippo Village and Cipto Mangunkusumo Hospital (CMH) from 2014 to 2018, the P63 expression and EBER-1 examinations were done by 4 pathologists. A total of 25 patients, 13 (52%) patients were male, ranging from age 30 – 79, with average 57,6 years old, located mostly in the frontal lobe in 8 patients (30.9%).

Result : From the research results obtained positive P63 results in 20 cases (80%), while the EBER test was negative for all 25 patients. Further analysis with software SPSS 25 proving that P63 expression is not associated with germinal center B-cell type (GCB) or non-GCB type (p-value 0,87). Neither, P63 have any association with Ki67 with p-value of 1.00.

Conclusions : This study concludes that there is a possibility that PCNSL cases in Indonesia are not associated with Epstein-Barr virus infection, but most of the cases will have a poor prognosis as indicated by P63 expression.

References

1. Olson JE. The continuing increase in the incidence of primary central nervous system non-Hodgkin lymphoma: A surveillance, epidemiology, and end results analysis. Cancer 2002; 95(7): 1504-1510. https://doi.org/10.1002/cncr.10851

2. Carbone A, Vaccher E, Gloghini A, Pantanowitz L, Abayomi A, de Paoli P, et al. Diagnosis and management of lymphomas and other cancers in HIV-infected patients. Nat Rev Clin Oncol 2014; 11(4): 223-238. https://doi.org/10.1038/nrclinonc.2014.31

3. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW. WHO Classification of Tumors of Haematopietic and Lymphoid Tissues. 4th ed. Lyon, France: IARC Press; 2008. p. 240-1.

4. Tun HW, Personett D, Baskerville KA, Menke DM, Jaeckle KA,Kreinest P, et al. Pathway analysis of primary central nervous system lymphoma. Blood 2008; 111(6): 3200-10. https://doi.org/10.1182/blood-2007-10-119099

5. Shiels MS, Pfeiffer RM, Besson C, et al. Trends in primary central nervous system lymphoma incidence and survival in the U.S.Br J Haematol. 2016;174(3):417-424. https://doi.org/10.1111/bjh.14073

6. Mahadevan A, Rao C, Shanmugham M, Shankar S. Primary central nervous system diffuse large B-cell lymphoma in the immunocompetent: Immunophenotypic subtypes and Epstein-Barr virus association. Journal of Neurosciences in Rural Practice. 2015; 6(01):008-014. https://doi.org/10.4103/0976-3147.143171

7. Gloghini A, Carbone A. Primary central nervous system lymphoma. Journal of Neurosciences in Rural Practice. 2015; 6(1): 002-003. https://doi.org/10.4103/0976-3147.143162

8. Wang J, Guo Z, Ma E, Xing D, Qiu B, Wang Y. Diagnosis and treatment of primary central nervous system lymphoma: A report of nine cases and literature review. Oncology Letters. 2015; 9(4): 1795-1801. https://doi.org/10.3892/ol.2015.2903

9. Rubenstein J, Ferreri AJ, Pittaluga S. Primary lymphoma of the central nervous system: epidemiology, pathology and current approaches to diagnosis, prognosis and treatment. Leuk Lymphoma. 2008;49(Suppl 1):43–51. https://doi.org/10.1080/10428190802311441

10. Hedvat C, Teruya-Feldstein J, Puig P, Capodieci P, Dudas M, Pica N et al. Expression of p63 in Diffuse Large B-Cell Lymphoma. Applied Immunohistochemistry & Molecular Morphology. 2005;13(3):237-242. https://doi.org/10.1097/01.pai.0000142160.52670.ce

11. Tandon A, Challa S, Shanmugam M, Gopalan S, Paul R, Digumarthi R. Epstein-Barr virus as a possible etiologic agent in primary central nervous system lymphoma in immunocompetent individuals. Neurology India. 2009; 57(1): 36-40. http://dx.doi.org/10.4103/0028-3886.48813

12. Kleinschmidt-DeMasters B, Damek D, Lillehei K, Dogan A, Giannini C. Epstein Barr Virus-Associated Primary CNS Lymphomas in Elderly Patients on Immunosuppressive Medications. Journal of Neuropathology & Experimental Neurology. 2008; 67(11):1103-1111. https://doi.org/10.1097/nen.0b013e31818beaea

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Published

2025-02-24

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Section

Clinical Research