Virus de Epstein-Barr y su relación con el desarrollo del cáncer

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Abstract

RESUMEN El virus de Epstein-Barr (VEB) es un agente infeccioso que tiene tropismo por células linfoides y ocasionalmente por células epiteliales. La Agencia Internacional para la Investigación sobre Cáncer (IARC, por su sigla en inglés) lo clasificó hace 20 años como carcinógeno de tipo I, porque durante la infección latente expresa diferentes proteínas o micro-ARN con capacidad oncogénica, por lo que las células infectadas tendrían el potencial de desarrollar cáncer. Esto se ha demostrado en algunos tipos de cáncer como linfomas, carcinoma nasofaríngeo y cáncer gástrico, mientras que la asociación no es completamente clara en los cánceres de mama y pulmón. La presente revisión describe, profundiza y analiza la relación del VEB con dichos tipos de cáncer, así como los métodos diagnósticos empleados para su detección. Finalmente, se plantean preguntas cuyas respuestas podrían contribuir al conocimiento de los mecanismos moleculares involucrados en la relación VEB-cáncer.

Translated abstract

SUMMARY Relationship between Epstein-Barr virus and cancer development Epstein-Barr virus (EBV) is an infectious agent with tropism for lymphoid cells and occasionally for epithelial cells. Twenty years ago it was classified by the International Agency for Research on Cancer (IARC) as type I carcinogen, because during latent infection it expresses different proteins or microRNAs with oncogenic ability, so that infected cells could potentially develop cancer. This association has been shown in some cancers such as lymphoma, nasopharyngeal carcinoma and gastric cancer, while the association has not been completely clear in breast and lung cancer. This review describes, deepens and analyzes the relationship between EVB and the aforementioned types of cancer, as well as diagnostic methods for its detection. Finally, this paper poses different questions whose answers could contribute to understand the molecular mechanisms involved in the EVB-cancer relationship.

Translated abstract

RESUMO O vírus de Epstein-Barr (VEB) é um agente infeccioso que tem tropismo pelas células linfóides e, ocasionalmente, por células epiteliais. A Agência Internacional de Investigação do Câncer (IARC, por sua sigla do Inglês) classificou-o há 20 anos como substância cancerígena tipo I, devido a que durante a infecção latente expressa diferentes proteínas ou micro-ARN com capacidade oncogênica, de modo que as células infectadas têm o potencial de desenvolver câncer. Isto tem sido demonstrado em alguns tipos de câncer tais como linfomas, carcinoma da nasofaringe e câncer gástrico, enquanto que a associação não é inteiramente claro nos câncer da mama e do pulmão. Esta revisão descreve, analisa os aprofunda a relação do VEB com os mencionados tipos de câncer, bem como os métodos de diagnóstico para a sua detecção. Finalmente, planteiam se questões cujas respostas poderiam contribuir na compreensão dos mecanismos moleculares envolvidos na relação VEB-câncer.

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Most cited references 93

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Biological agents. Volume 100 B. A review of human carcinogens.

(2012)

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Clonal proliferations of cells infected with Epstein-Barr virus in preinvasive lesions related to nasopharyngeal carcinoma.

R. Pathmanathan, U. Prasad, R. Sadler … (1995)

The Epstein-Barr virus (EBV) is consistently detected in patients with nasopharyngeal carcinoma. To determine whether EBV infection is an early, initiating event in the development of this malignant tumor, we screened nasopharyngeal-biopsy samples, most of which were archival, for preinvasive lesions, including dysplasia and carcinoma in situ. Preinvasive lesions were found in 11 samples, which were tested for the presence of EBV. EBV infection was detected with in situ hybridization for EBV-encoded RNAs (EBERs) and by immunohistochemical staining for latent membrane protein 1 (LMP-1). The larger samples were also tested for the EBV genome with the use of Southern blotting. The expression of specific EBV RNAs was determined by the amplification of complementary DNA with the polymerase chain reaction. Evidence of EBV infection was detected in all 11 tissue samples with dysplasia or carcinoma in situ. EBERs were identified in all eight samples tested, and LMP-1 was detected in all six of the tested samples. Six of the seven samples tested for the EBV termini contained clonal EBV DNA: Transcription of the latent EBV gene products, EBV nuclear antigen 1, LMP-1, LMP-2A, and the BamHI-A fragment, was detected in most of the samples. Viral proteins characteristic of lytic lesions were not detected. Preinvasive lesions of the nasopharynx are infected with EBV. The EBV DNA is clonal, indicating that the lesions represent a focal cellular growth that arose from a single EBV-infected cell and that EBV infection is an early, possibly initiating event in the development of nasopharyngeal carcinoma. Preinvasive lesions contain EBV RNAs that are characteristic of latent infection but not the viral proteins that are characteristic of lytic infection. The detection of the EBV-transforming gene, LMP-1, in all the neoplastic cells suggests that its expression is essential for preinvasive epithelial proliferations associated with nasopharyngeal carcinoma.

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Clinicopathological and molecular characteristics of Epstein-Barr virus-associated gastric carcinoma: a meta-analysis.

Seo-Jeon Kim, Jon Geun Lee, Won Suk An … (2009)

There is conflicting data regarding the clinicopathological significance of the risk factors associated with Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC). To address this controversy, we performed a meta-analysis for the clinicopathological and molecular characteristics of EBVaGC. The relevant published studies were reviewed according to the defined selection criteria. The effect sizes of the outcome parameters were estimated by an odds ratio or a weighted mean difference. This meta-analysis included 48 studies that encompassed a total of 9738 patients. The frequency of EBVaGC was 8.8%, and EBVaGC was significantly associated with ethnicity. It was more predominant in men and in younger individuals. Interestingly, EBVaGC was more prevalent in Caucasian and Hispanic patients than in Asian ones. EBVaGC developed most often in the cardia and body, and it generally showed the diffuse histological type. EBV was highly prevalent in the patients with lymphoepithelial carcinoma. EBVaGC was closely associated with remnant cancer and a CpG island methylator-high status, but not with Helicobacter pylori infection, a TP53 expression, and p53 mutation. In addition, EBVaGC was not significantly associated with the depth of invasion, lymph node metastasis, or the clinical stage. The clinicopathological and molecular characteristics of EBVaGC are quite different from those of conventional gastric adenocarcinoma. However, further study is needed to determine the effect of EBV on the survival of EBVaGC patients.