Detección del Virus de Epstein-Barr en linfoma mediante qPCR //Detection of Epstein-Barr Virus (EBV) in lymphoma through qPCR
DOI:
https://doi.org/10.29076/issn.2528-7737vol11iss26.2018pp126-133pPalabras clave:
Linfoma, Hodking, No Hodking, PCR, Virus Epstein BarrResumen
Virus Epstein Barr (VEB) ha sido relacionado con una serie de tumores malignos de origen epitelial y linfoide. Existe una clara correlación entre este virus y enfermedades linfoproliferativas como Linfoma de Burkitt (LB), Linfoma Hodgkin (LH), Linfoma no Hodgkin (LNH) y carcinoma gástrico. Se han desarrollado diversas técnicas para la detección de VEB en células tumorales: hibridación in situ (RISH) que detecta RNAs (ácido ribonucleico) pequeños codificados para VEB (EBERs) en las células con infección latente, considerado el estándar de oro para la identificación del virus; la reacción en cadena de la polimerasa (PCR) que permite la detección de la cepa viral y representa un ensayo importarte en el diagnóstico del virus. Se realizó un estudio retrospectivo a partir de muestras de tejidos en parafina de pacientes con linfoma y se buscó al virus mediante PCR y RISH. La prevalencia del virus fue de 58,82%, el género más afectado fue el masculino y el grupo más afectado fue el de 31/40 años. La presencia del virus fue similar en ambos tipos de linfoma: Hodking y No Hodking. La técnica de RISH se mostró más eficiente para detectar la presencia del virus.
Abstract
Epstein Barr Virus (EBV) is linked to a number of malignant tumors of epithelial and lymphoid origin. There is a strong correlation between this virus and lymphoproliferative diseases such as Burkitt's lymphoma (BL), Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL) and gastric carcinoma. There are various techniques developed to detect EBV in tumor cells: in situ hybridization (ISH) detects small coded RNAs (ribonucleic acid) to VEB (EBERs) in latently infected cells. This is considered the gold standard for virus identification. The polymerase chain reaction (PCR) allows the detection of the viral strain and represents an important fact in the virus diagnose. We conducted a retrospective study in paraffin from tissue samples of patients with lymphoma and we sought the virus through PCR and RISH. The virus prevalence was 58.82%, the most affected gender was male and the most affected group was 31/40 years. The virus was similar in both types of lymphoma: Hodgkin and non-Hodgkin. RISH technique seemed to be more efficient to detect the virus.
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Referencias
Ahmed, W., Philip, P. S., Tariq, S., & Khan, G. (2014). Epstein-Barr Virus-Encoded Small RNAs (EBERs) Are Present in Fractions Related to Exosomes Released by EBV-Transformed Cells. PLoS ONE, 9(6), e99163. https://doi.org/10.1371/journal.pone.0099163
Almasri, N. M., & Khalidi, H. S. (2004). Epstein-Barr virus expression in Hodgkin’s disease in Jordan. Saudi Medical Journal, 25(6), 770–775.
Ambinder, R. F., & Mann, R. B. (1994). Detection and characterization of Epstein-Barr virus in clinical specimens. The American Journal of Pathology, 145(2), 239–252.
Cool, C. D., & Bitter, M. A. (1997). The malignant lymphomas of Kenya: morphology, immunophenotype, and frequency of Epstein-Barr virus in 73 cases. Human Pathology, 28(9), 1026–1033.
Fox, C. P., Shannon-Lowe, C., & Rowe, M. (2011). Deciphering the role of Epstein-Barr virus in the pathogenesis of T and NK cell lymphoproliferations. Herpesviridae, 2, 8–8. https://doi.org/10.1186/2042-4280-2-8
Gequelin, L. C. F., Riediger, I. N., Nakatani, S. M., Biondo, A. W., & Bonfim, C. M. (2011). Epstein-Barr virus: general factors, virus-related diseases and measurement of viral load after transplant. Revista Brasileira de Hematologia E Hemoterapia, 33(5), 383–388. https://doi.org/10.5581/1516-8484.20110103
Glaser, S. L., Lin, R. J., Stewart, S. L., Ambinder, R. F., Jarrett, R. F., Brousset, P., … Claviez, A. (1997). Epstein-Barr virus-associated Hodgkin’s disease: epidemiologic characteristics in international data. International Journal of Cancer, 70(4), 375–382.
Gulley, M. L., & Tang, W. (2008). Laboratory Assays for Epstein-Barr Virus-Related Disease. The Journal of Molecular Diagnostics : JMD, 10(4), 279–292. https://doi.org/10.2353/jmoldx.2008.080023
Hassan, R., White, L. R., Stefanoff, C. G., de Oliveira, D. E., Felisbino, F. E., Klumb, C. E., … Zalcberg, I. R. (2006). Epstein-Barr Virus (EBV) detection and typing by PCR: a contribution to diagnostic screening of EBV-positive Burkitt’s lymphoma. Diagnostic Pathology, 1, 17–17. https://doi.org/10.1186/1746-1596-1-17
Iizasa, H., Nanbo, A., Nishikawa, J., Jinushi, M., & Yoshiyama, H. (2012). Epstein-Barr Virus (EBV)-associated Gastric Carcinoma. Viruses, 4(12), 3420–3439. https://doi.org/10.3390/v4123420
Israel, B. F., & Kenney, S. C. (2003). Virally targeted therapies for EBV-associated malignancies. Oncogene, 22(33), 5122–5130.
Ko, Y.-H. (2015). EBV and human cancer. Exp Mol Med, 47, e130.
Lung, R. W.-M., Tong, J. H.-M., & To, K.-F. (2013). Emerging roles of small Epstein-Barr virus derived non-coding RNAs in epithelial malignancy. International Journal of Molecular Sciences, 14(9), 17378–17409. https://doi.org/10.3390/ijms140917378
Rickinson, A. (2002). Epstein-Barr Virus, 82(1), 109–13.
Roschewski, M., & Wilson, W. H. (2012). EBV-associated lymphomas in adults. Best Practice & Research. Clinical Haematology, 25(1), 75–89. https://doi.org/10.1016/j.beha.2012.01.005
Shannon-Lowe, C., & Rowe, M. (2011). Epstein-Barr Virus Infection of Polarized Epithelial Cells via the Basolateral Surface by Memory B Cell-Mediated Transfer Infection. PLoS Pathogens, 7(5), e1001338. https://doi.org/10.1371/journal.ppat.1001338
Sughayer, M. A., Haddad, H. A., Al-Yousef, R. M., El-Khateeb, M., & Abu-Rass, H. (2014). Epstein-Barr virus and Hodgkin lymphoma in Jordan. Hematology/oncology and Stem Cell Therapy, 7(2), 85–89. https://doi.org/10.1016/j.hemonc.2013.12.002
Tumwine, L. K., Orem, J., Kerchan, P., Byarugaba, W., & Pileri, S. A. (2010). EBV, HHV8 and HIV in B cell non Hodgkin lymphoma in Kampala, Uganda. Infectious Agents and Cancer, 5, 12. https://doi.org/10.1186/1750-9378-5-12
Urayama, K. Y., Jarrett, R. F., Hjalgrim, H., Diepstra, A., Kamatani, Y., Chabrier, A., … McKay, J. D. (2012). Genome-wide association study of classical Hodgkin lymphoma and Epstein-Barr virus status-defined subgroups. Journal of the National Cancer Institute, 104(3), 240–253. https://doi.org/10.1093/jnci/djr516
Vasef, M., Ubaidat, M., Khalidi, H., Almasri, N., Al-Abbadi, M., & Annab, H. (2004). Association between Epstein-Barr virus and classic Hodgkin lymphoma in Jordan: a comparative study with Epstein-Barr virus-associated Hodgkin lymphoma in North America, 97(3), 273–7.
Weinreb, M., Day, P. J., Niggli, F., Powell, J. E., Raafat, F., Hesseling, P. B., … Mann, J. R. (1996). The role of Epstein-Barr virus in Hodgkin’s disease from different geographical areas. Archives of Disease in Childhood, 74(1), 27–31.
Young, L. S., & Murray, P. G. (2003). Epstein-Barr virus and oncogenesis: from latent genes to tumours. Oncogene, 22(33), 5108–5121. https://doi.org/10.1038/sj.onc.1206556
Ahmed, W., Philip, P. S., Tariq, S., & Khan, G. (2014). Epstein-Barr Virus-Encoded Small RNAs (EBERs) Are Present in Fractions Related to Exosomes Released by EBV-Transformed Cells. PLoS ONE, 9(6), e99163. https://doi.org/10.1371/journal.pone.0099163
Almasri, N. M., & Khalidi, H. S. (2004). Epstein-Barr virus expression in Hodgkin’s disease in Jordan. Saudi Medical Journal, 25(6), 770–775.
Ambinder, R. F., & Mann, R. B. (1994). Detection and characterization of Epstein-Barr virus in clinical specimens. The American Journal of Pathology, 145(2), 239–252.
Cool, C. D., & Bitter, M. A. (1997). The malignant lymphomas of Kenya: morphology, immunophenotype, and frequency of Epstein-Barr virus in 73 cases. Human Pathology, 28(9), 1026–1033.
Fox, C. P., Shannon-Lowe, C., & Rowe, M. (2011). Deciphering the role of Epstein-Barr virus in the pathogenesis of T and NK cell lymphoproliferations. Herpesviridae, 2, 8–8. https://doi.org/10.1186/2042-4280-2-8
Gequelin, L. C. F., Riediger, I. N., Nakatani, S. M., Biondo, A. W., & Bonfim, C. M. (2011). Epstein-Barr virus: general factors, virus-related diseases and measurement of viral load after transplant. Revista Brasileira de Hematologia E Hemoterapia, 33(5), 383–388. https://doi.org/10.5581/1516-8484.20110103
Glaser, S. L., Lin, R. J., Stewart, S. L., Ambinder, R. F., Jarrett, R. F., Brousset, P., … Claviez, A. (1997). Epstein-Barr virus-associated Hodgkin’s disease: epidemiologic characteristics in international data. International Journal of Cancer, 70(4), 375–382.
Gulley, M. L., & Tang, W. (2008). Laboratory Assays for Epstein-Barr Virus-Related Disease. The Journal of Molecular Diagnostics : JMD, 10(4), 279–292. https://doi.org/10.2353/jmoldx.2008.080023
Hassan, R., White, L. R., Stefanoff, C. G., de Oliveira, D. E., Felisbino, F. E., Klumb, C. E., … Zalcberg, I. R. (2006). Epstein-Barr Virus (EBV) detection and typing by PCR: a contribution to diagnostic screening of EBV-positive Burkitt’s lymphoma. Diagnostic Pathology, 1, 17–17. https://doi.org/10.1186/1746-1596-1-17
Iizasa, H., Nanbo, A., Nishikawa, J., Jinushi, M., & Yoshiyama, H. (2012). Epstein-Barr Virus (EBV)-associated Gastric Carcinoma. Viruses, 4(12), 3420–3439. https://doi.org/10.3390/v4123420
Israel, B. F., & Kenney, S. C. (2003). Virally targeted therapies for EBV-associated malignancies. Oncogene, 22(33), 5122–5130.
Ko, Y.-H. (2015). EBV and human cancer. Exp Mol Med, 47, e130.
Lung, R. W.-M., Tong, J. H.-M., & To, K.-F. (2013). Emerging roles of small Epstein-Barr virus derived non-coding RNAs in epithelial malignancy. International Journal of Molecular Sciences, 14(9), 17378–17409. https://doi.org/10.3390/ijms140917378
Rickinson, A. (2002). Epstein-Barr Virus, 82(1), 109–13.
Roschewski, M., & Wilson, W. H. (2012). EBV-associated lymphomas in adults. Best Practice & Research. Clinical Haematology, 25(1), 75–89. https://doi.org/10.1016/j.beha.2012.01.005
Shannon-Lowe, C., & Rowe, M. (2011). Epstein-Barr Virus Infection of Polarized Epithelial Cells via the Basolateral Surface by Memory B Cell-Mediated Transfer Infection. PLoS Pathogens, 7(5), e1001338. https://doi.org/10.1371/journal.ppat.1001338
Sughayer, M. A., Haddad, H. A., Al-Yousef, R. M., El-Khateeb, M., & Abu-Rass, H. (2014). Epstein-Barr virus and Hodgkin lymphoma in Jordan. Hematology/oncology and Stem Cell Therapy, 7(2), 85–89. https://doi.org/10.1016/j.hemonc.2013.12.002
Tumwine, L. K., Orem, J., Kerchan, P., Byarugaba, W., & Pileri, S. A. (2010). EBV, HHV8 and HIV in B cell non Hodgkin lymphoma in Kampala, Uganda. Infectious Agents and Cancer, 5, 12. https://doi.org/10.1186/1750-9378-5-12
Urayama, K. Y., Jarrett, R. F., Hjalgrim, H., Diepstra, A., Kamatani, Y., Chabrier, A., … McKay, J. D. (2012). Genome-wide association study of classical Hodgkin lymphoma and Epstein-Barr virus status-defined subgroups. Journal of the National Cancer Institute, 104(3), 240–253. https://doi.org/10.1093/jnci/djr516
Vasef, M., Ubaidat, M., Khalidi, H., Almasri, N., Al-Abbadi, M., & Annab, H. (2004). Association between Epstein-Barr virus and classic Hodgkin lymphoma in Jordan: a comparative study with Epstein-Barr virus-associated Hodgkin lymphoma in North America, 97(3), 273–7.
Weinreb, M., Day, P. J., Niggli, F., Powell, J. E., Raafat, F., Hesseling, P. B., … Mann, J. R. (1996). The role of Epstein-Barr virus in Hodgkin’s disease from different geographical areas. Archives of Disease in Childhood, 74(1), 27–31.
Young, L. S., & Murray, P. G. (2003). Epstein-Barr virus and oncogenesis: from latent genes to tumours. Oncogene, 22(33), 5108–5121. https://doi.org/10.1038/sj.onc.1206556
Ahmed, W., Philip, P. S., Tariq, S., & Khan, G. (2014). Epstein-Barr Virus-Encoded Small RNAs (EBERs) Are Present in Fractions Related to Exosomes Released by EBV-Transformed Cells. PLoS ONE, 9(6), e99163. https://doi.org/10.1371/journal.pone.0099163
Almasri, N. M., & Khalidi, H. S. (2004). Epstein-Barr virus expression in Hodgkin’s disease in Jordan. Saudi Medical Journal, 25(6), 770–775.
Ambinder, R. F., & Mann, R. B. (1994). Detection and characterization of Epstein-Barr virus in clinical specimens. The American Journal of Pathology, 145(2), 239–252.
Cool, C. D., & Bitter, M. A. (1997). The malignant lymphomas of Kenya: morphology, immunophenotype, and frequency of Epstein-Barr virus in 73 cases. Human Pathology, 28(9), 1026–1033.
Fox, C. P., Shannon-Lowe, C., & Rowe, M. (2011). Deciphering the role of Epstein-Barr virus in the pathogenesis of T and NK cell lymphoproliferations. Herpesviridae, 2, 8–8. https://doi.org/10.1186/2042-4280-2-8
Gequelin, L. C. F., Riediger, I. N., Nakatani, S. M., Biondo, A. W., & Bonfim, C. M. (2011). Epstein-Barr virus: general factors, virus-related diseases and measurement of viral load after transplant. Revista Brasileira de Hematologia E Hemoterapia, 33(5), 383–388. https://doi.org/10.5581/1516-8484.20110103
Glaser, S. L., Lin, R. J., Stewart, S. L., Ambinder, R. F., Jarrett, R. F., Brousset, P., … Claviez, A. (1997). Epstein-Barr virus-associated Hodgkin’s disease: epidemiologic characteristics in international data. International Journal of Cancer, 70(4), 375–382.
Gulley, M. L., & Tang, W. (2008). Laboratory Assays for Epstein-Barr Virus-Related Disease. The Journal of Molecular Diagnostics : JMD, 10(4), 279–292.
Hassan, R., White, L. R., Stefanoff, C. G., de Oliveira, D. E., Felisbino, F. E., Klumb, C. E., … Zalcberg, I. R. (2006). Epstein-Barr Virus (EBV) detection and typing by PCR: a contribution to diagnostic screening of EBV-positive Burkitt’s lymphoma. Diagnostic Pathology, 1, 17–17. https://doi.org/10.1186/1746-1596-1-17
Iizasa, H., Nanbo, A., Nishikawa, J., Jinushi, M., & Yoshiyama, H. (2012). Epstein-Barr Virus (EBV)-associated Gastric Carcinoma. Viruses, 4(12), 3420–3439. https://doi.org/10.3390/v4123420
Israel, B. F., & Kenney, S. C. (2003). Virally targeted therapies for EBV-associated malignancies. Oncogene, 22(33), 5122–5130.
Ko, Y.-H. (2015). EBV and human cancer. Exp Mol Med, 47, e130.
Lung, R. W.-M., Tong, J. H.-M., & To, K.-F. (2013). Emerging roles of small Epstein-Barr virus derived non-coding RNAs in epithelial malignancy. International Journal of Molecular Sciences, 14(9), 17378–17409. https://doi.org/10.3390/ijms140917378
Rickinson, A. (2002). Epstein-Barr Virus, 82(1), 109–13.
Roschewski, M., & Wilson, W. H. (2012). EBV-associated lymphomas in adults. Best Practice & Research. Clinical Haematology, 25(1), 75–89. https://doi.org/10.1016/j.beha.2012.01.005
Shannon-Lowe, C., & Rowe, M. (2011). Epstein-Barr Virus Infection of Polarized Epithelial Cells via the Basolateral Surface by Memory B Cell-Mediated Transfer Infection. PLoS Pathogens, 7(5), e1001338. https://doi.org/10.1371/journal.ppat.1001338
Sughayer, M. A., Haddad, H. A., Al-Yousef, R. M., El-Khateeb, M., & Abu-Rass, H. (2014). Epstein-Barr virus and Hodgkin lymphoma in Jordan. Hematology/oncology and Stem Cell Therapy, 7(2), 85–89. https://doi.org/10.1016/j.hemonc.2013.12.002
Tumwine, L. K., Orem, J., Kerchan, P., Byarugaba, W., & Pileri, S. A. (2010). EBV, HHV8 and HIV in B cell non Hodgkin lymphoma in Kampala, Uganda. Infectious Agents and Cancer, 5, 12. https://doi.org/10.1186/1750-9378-5-12
Urayama, K. Y., Jarrett, R. F., Hjalgrim, H., Diepstra, A., Kamatani, Y., Chabrier, A., … McKay, J. D. (2012). Genome-wide association study of classical Hodgkin lymphoma and Epstein-Barr virus status-defined subgroups. Journal of the National Cancer Institute, 104(3), 240–253.
Vasef, M., Ubaidat, M., Khalidi, H., Almasri, N., Al-Abbadi, M., & Annab, H. (2004). Association between Epstein-Barr virus and classic Hodgkin lymphoma in Jordan: a comparative study with Epstein-Barr virus-associated Hodgkin lymphoma in North America, 97(3), 273–7.
Weinreb, M., Day, P. J., Niggli, F., Powell, J. E., Raafat, F., Hesseling, P. B., … Mann, J. R. (1996). The role of Epstein-Barr virus in Hodgkin’s disease from different geographical areas. Archives of Disease in Childhood, 74(1), 27–31.
Young, L. S., & Murray, P. G. (2003). Epstein-Barr virus and oncogenesis: from latent genes to tumours. Oncogene, 22(33), 5108–5121. https://doi.org/10.1038/sj.onc.1206556
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