Epstein–Barr Virus Infection in Pediatric Hodgkin Lymphoma: EBER Analysis by In Situ Hybridization
DOI:
https://doi.org/10.66778/RM.v09n01.07Keywords:
Epstein–Barr virus (EBV), Hodgkin Lymphoma (HL), EBV encoded small RNAs( EBERs), in situ hybridization (ISH)Abstract
Introduction: Epstein–Barr virus (EBV) has been associated with various neoplasms, including pediatric Hodgkin lymphoma (HL). This relationship is more evident in developing countries, where primary infection occurs at an early age due to the high viral burden in the population. In Central America, however, studies exploring its presence in these tumors are limited, hindering a full understanding of its role in the etiopathogenesis of pediatric HL and restricting the development of diagnostic and therapeutic strategies tailored to the regional context. Objective: To investigate the presence of EBV in paraffin-embedded biopsy samples from pediatric HL cases treated at the National Children’s Hospital Benjamín Bloom. Materials and Methods: EBV infection in tumor cells was assessed using in situ hybridization (ISH) targeting EBV-encoded small RNAs (EBERs), considered the gold standard for detecting latent infection. Results: The findings showed that 71.42% of samples were positive for EBERs, confirming the presence of the virus and its potentially strong association with classical Hodgkin lymphoma (cHL) in this pediatric population. Conclusion: Overall, these results reinforce the important role EBV may play in the pathogenesis of pediatric cHL in regions with high viral endemicity, such as Central America. ISH remains an indispensable diagnostic tool for identifying latent infection, providing valuable information with potential clinical implications. These findings are particularly relevant in the context of emerging immunotherapies directed against viral antigens, which may pave the way for more personalized treatments for patients with EBV-positive tumors. Furthermore, they highlight the need to expand regional research by incorporating larger sample sizes and integrating clinical and immunological variables to achieve a more comprehensive understanding of the interaction among EBV infection, the host, and the neoplasm.
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References
Aggarwal, P., & Limaiem, F. (2025). Células de Reed-Sternberg Introducción. 6–13. https://www.ncbi.nlm.nih.gov/books/NBK542333/
Alejandro, M. (2012). Caracterización de variantes del virus de Epstein Barr en la infección aguda en pacientes pediátricos y su comparación con linfomas pediátricos EBV +.
Begić, V., Korać, P., Gašparov, S., Rozman, M., Simicic, P., & Zidovec-Lepej, S. (2022). Molecular Characterisation of Epstein–Barr Virus in Classical Hodgkin Lymphoma. International Journal of Molecular Sciences, 23(24). https://doi.org/10.3390/ijms232415635
Beltramino, M., Calmet, R., & Gatica Valdes, M. (2005). Virus de Epstein-Barr y su relación con el desarrollo de enfermedades linfoproliferativas. Hematología (B. Aires), 8, 39–54.
Bröckelmann, P. J., Eichenauer, D. A., Jakob, T., Follmann, M., Engert, A., & Skoetz, N. (2018). Clinical practice guideline: Hodgkin lymphoma in adults—diagnosis, treatment, and follow-up. Deutsches Arzteblatt International, 115(31–32), 535–540. https://doi.org/10.3238/arztebl.2018.0535
Diepstra, A., Nolte, I. M., van den Berg, A., Magpantay, L. I., Martínez-Maza, O., & Levin, L. I. (2023). Elevated serum TARC levels precede classic Hodgkin lymphoma diagnosis by several years. Blood, 142(22), 1928–1931. https://doi.org/10.1182/blood.2023020959
Farrell, P. J., & Farrell, P. J. (2025). Epstein – Barr virus functional RNAs as part of its immune evasion strategy : a role for EBER1 ? December. https://doi.org/10.1098/rsob.250088/2811425/rsob.250088.pdf
Fok, V., Friend, K., & Steitz, J. A. (2006). Epstein-Barr virus noncoding RNAs are confined to the nucleus, whereas their partner, the human La protein, undergoes nucleocytoplasmic shuttling. Journal of Cell Biology, 173(3), 319–325. https://doi.org/10.1083/jcb.200601026
Gulley, M. L., & Tang, W. (2008). Laboratory assays for Epstein-Barr virus-related disease. Journal of Molecular Diagnostics, 10(4), 279–292. https://doi.org/10.2353/jmoldx.2008.080023
Haleem Abusalah, et al. (2024). Recent Advances in Diagnostic Approaches for Epstein–Barr Virus. Journal Pathogens, 10(10), 1–17. https://doi.org/https://doi.org/10.3390/pathogens9030226
Han, Y., Liu, D., & Li, L. (2020). PD-1/PD-L1 pathway: current researches in cancer. American Journal of Cancer Research, 10(3), 727–742. http://www.ncbi.nlm.nih.gov/pubmed/32266087
Hui, K. F., Yiu, S. P. T., Tam, K. P., & Chiang, A. K. S. (2019). Viral-targeted strategies against EBV-associated lymphoproliferative diseases. Frontiers in Oncology, 9(FEB), 1–18. https://doi.org/10.3389/fonc.2019.00081
Iwakiri, D. (2014). Epstein-Barr virus-encoded RNAs: Key molecules in viral pathogenesis. Cancers, 6(3), 1615–1630. https://doi.org/10.3390/cancers6031615
Ko, Y. H. (2015). Editorial: EBV and human cancer. Experimental and Molecular Medicine, 47(1), e130--3. https://doi.org/10.1038/emm.2014.109
Li, H., Lee, C. Y., & Delecluse, H. J. (2025). Epstein–Barr virus lytic replication and cancer. Current Opinion in Virology, 70, 101438. https://doi.org/10.1016/j.coviro.2024.101438
Liu, T. Y., Wu, S. J., Huang, M. H., Lo, F. Y., Tsai, M. H., Tsai, C. H., Hsu, S. M., & Lin, C. W. (2010). EBV-positive Hodgkin lymphoma is associated with suppression of p21cip1/waf1and a worse prognosis. Molecular Cancer, 9, 1–12. https://doi.org/10.1186/1476-4598-9-32
Mautner, J. (2018). Clinical implications of Epstein-Barr virus strain diversity. Journal of Immunological Sciences, 2(3), 51–55. https://doi.org/10.29245/2578-3009/2018/3.1145
Murata, T., Sugimoto, A., Inagaki, T., Yanagi, Y., Watanabe, T., Sato, Y., & Kimura, H. (2021). Molecular basis of epstein–barr virus latency establishment and lytic reactivation. Viruses, 13(12), 1–20. https://doi.org/10.3390/v13122344
Nagpal, P., Akl, M. R., Ayoub, N. M., Tomiyama, T., Cousins, T., Tai, B., Carroll, N., Nyrenda, T., Bhattacharyya, P., Harris, M. B., Goy, A., Pecora, A., & Suh, S. S. (2016). Pediatric Hodgkin lymphoma- biomarkers, drugs, and clinical trials for translational science and medicine. Oncotarget, 7(41), 67551–67573. https://doi.org/10.18632/oncotarget.11509
Patel, P. G., Selvarajah, S., Boursalie, S., How, N. E., Ejdelman, J., Guerard, K. P., Bartlett, J. M., Lapointe, J., Park, P. C., Okello, J. B. A., & Berman, D. M. (2016). Preparation of formalin-fixed paraffin-embedded tissue cores for both RNA and DNA extraction. Journal of Visualized Experiments, 2016(114), 1–10. https://doi.org/10.3791/54299
Samanta, M., & Takada, K. (2010). Modulation of innate immunity system by Epstein-Barr virus-encoded non-coding RNA and oncogenesis. Cancer Science, 101(1), 29–35. https://doi.org/10.1111/j.1349-7006.2009.01377.x
Seifert, M., Scholtysik, R., & Küppers, R. (2019). Origin and pathogenesis of B cell lymphomas. In Methods in Molecular Biology (Vol. 1956). https://doi.org/10.1007/978-1-4939-9151-8_1
Shannon-Lowe, C., & Rickinson, A. (2019). The Global Landscape of EBV-Associated Tumors. Frontiers in Oncology, 9(August), 1–23. https://doi.org/10.3389/fonc.2019.00713
Shannon-Lowe, C., Rickinson, A. B., & Bell, A. I. (2017). Epstein-barr virus-associated lymphomas. Philosophical Transactions of the Royal Society B: Biological Sciences, 372(1732). https://doi.org/10.1098/rstb.2016.0271
Smatti, M. K., Al-Sadeq, D. W., Ali, N. H., Pintus, G., Abou-Saleh, H., & Nasrallah, G. K. (2018). Epstein-barr virus epidemiology, serology, and genetic variability of LMP-1 oncogene among healthy population: An update. Frontiers in Oncology, 8(JUN). https://doi.org/10.3389/fonc.2018.00211
Song, H., Lim, Y., Im, H., Bae, J. M., Kang, G. H., Ahn, J., Baek, D., Kim, T. Y., Yoon, S. S., & Koh, Y. (2019). Interpretation of EBV infection in pan-cancer genome considering viral life cycle: LiEB (Life cycle of Epstein-Barr virus). Scientific Reports, 9(1), 1–10. https://doi.org/10.1038/s41598-019-39706-0
Yu, H., & Robertson, E. S. (2023). Epstein–Barr Virus History and Pathogenesis. Viruses, 15(3). https://doi.org/10.3390/v15030714
Zhang, Y., Lyu, H., Guo, R., Cao, X., Feng, J., Jin, X., Lu, W., & Zhao, M. (2023). Epstein‒Barr virus–associated cellular immunotherapy. Cytotherapy, 25(9), 903–912. https://doi.org/10.1016/j.jcyt.2023.04.003
Zijtregtop, E. A. M., Tromp, I., Dandis, R., Zwaan, C. M., Lam, K. H., Meyer-Wentrup, F. A. G., & Beishuizen, A. (2022). The Prognostic Value of Eight Immunohistochemical Markers Expressed in the Tumor Microenvironment and on Hodgkin Reed-Sternberg Cells in Pediatric Patients With Classical Hodgkin Lymphoma. Pathology and Oncology Research, 28(August), 1–8. https://doi.org/10.3389/pore.2022.1610482
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