O papel do epstein barr vírus na carcinogênese oral

Introduction: the squamous cell carcinoma (SCC) is the head and neck cancer of higher occurrence, representing about 90% of all these tumors. The SCC has several risk factors as smoking, alcohol and some oncogenic viruses, including the Epstein Barr virus (EBV). The EBV is a member of Herpesviridae family and has tropism for B lymphocytes and also for epithelial cells. Aim: the aim of this study was accomplish a review of the literature about the presence of the EBV in oral carcinomas. Conclusion: EBV is closely related to nasopharyngeal carcinoma, a SCC of high incidence in Southeast Asia, however its role in others oral SCC has not been proved.

Carga viral e genotipagem do vírus de Epstein-Barr (EBV) e análise da frequência das variantes do gene viral BNLF-1 em indivíduos portadores do vírus da imunodeficiência humana (HIV)

Indivíduos imunocomprometidos possuem maior risco de desenvolver linfomas associados ao EBV. A detecção desse vírus em sangue periférico e a determinação de sua carga viral podem ter importância na evolução clínica de indivíduos portadores do HIV. Foram avaliadas 156 amostras de pacientes HIVpositivos pela reação em cadeia da polimerase em tempo real (qPCR) para detecção e quantificação da carga viral do EBV. 123/156 (78,8%) casos apresentaram carga viral detectável para o EBV, sendo que a carga viral média foi de 6,9x10-3 cópias de EBV/célula. Foi detectada elevada carga viral do EBV em indivíduos com falha terapêutica ou sem HAART (p =0,0076), em coinfectados pelos EBVs 1 e 2 (p=0,0205), em pacientes com altas cargas de HIV (rho=0,27614, p=0,0005) e longos períodos de infecção pelo HIV (rho= 0,24164, p =0,0026) e os que apresentavam altos níveis de linfócitos T CD8 + (rho=0,19286, p =0,0159). A amplificação do gene EBNA-2 para realização da tipagem viral foi possível em 95/123 (77,2%) amostras, das quais 72 (75,8%) revelaram infecção pelo EBV-1, 9 (9,5%) pelo EBV-2 e 14 (14,7%) apresentavam coinfecção entre os EBVs 1 e 2. Esses dados estão de acordo com a literatura visto que o tipo 1 é predominante em países ocidentais e 70,0% da coorte era composta por indivíduos caucasianos e heterossexuais. A maioria dos pacientes que apresentaram coinfecção pelos EBVs 1 e 2 tiveram contagem de linfócitos T CD4 + entre 200 e 499 células/μL de sangue segundo classificação CDC (p =0,0272). Quanto a analise do gene BNLF-1, a amplificação foi possível em 99/123 (80,5%). Desses 50/99 (50,5%) apresentavam a deleção de 30pb no gene, enquanto 49/99 (49,5%) não a possuíam. Em conjunto, os resultados obtidos evidenciam deterioração do sistema imunitário, caracterizada...(Resumo completo, clicar acesso eletrônico abaixo)

Detecção do vírus Epstein-Barr (EBV) em adenocarcinomas gástricos procedentes dos estados do Ceará e de São Paulo

INTRODUÇÃO: O vírus Epstein-Barr (EBV) está associado a cerca de 10% dos adenocarcinomas gástricos, representando mais de 50 mil casos por ano no mundo. Apesar dos estudos realizados em várias partes do mundo, alguns aspectos clinicopatológicos permanecem controversos. OBJETIVOS: O presente estudo teve como objetivo analisar as características clinicopatológicas de casos de adenocarcinomas gástricos procedentes dos estados de São Paulo e Ceará, correlacionando-os com a detecção de EBV. MATERIAIS E MÉTODOS: Foram obtidos 192 casos de adenocarcinomas gástricos de hospitais dos estados de São Paulo e do Ceará, dos quais 160 foram submetidos à técnica de RNA-hibridização in situ para detecção de EBV. RESULTADOS: Dos 160 casos, 11 (6,9%) foram EBV-positivo, exibindo intensa marcação nuclear em células tumorais. Destes, dois casos também apresentaram linfócitos infiltrados marcados. Não encontramos marcação em tecido normal ou pré-neoplásico. São Paulo e Ceará apresentaram as frequências 3/60 (5%) e 8/100 (8%), respectivamente, e maior relação do EBV com indivíduos do sexo masculino, de idade avançada, com tumores do tipo intestinal, de estadiamento elevado e grau pouco a moderadamente diferenciado. Os casos do Ceará exibiram aumento relativo de tumores EBV(+) localizados na cárdia, enquanto os casos de São Paulo demonstraram aumento naqueles localizados no corpo gástrico. CONCLUSÃO: A frequência de tumores EBV(+) do presente estudo situa-se nos valores descritos na literatura mundial. Entre os achados, um deles não encontra paralelo na literatura mundial e refere-se ao elevado percentual de tumores EBV(+) no corpo gástrico observado nos casos de São Paulo.

Detecção do vírus Epstein-Barr em carcinoma espinocelular oral e mucosa oral na região de Araçatuba – SP, Brasil

Pós-graduação em Odontologia - FOA

Infecção pelo vírus de Epstein-Barr (EBV) e vírus do papiloma humano (HPV), expressão da proteína p53 e proliferação celular em carcinomas de nasofaringe e laringe

Pós-graduação em Patologia - FMB

Migração e invasão celular in vitro de células humanas expressando variantes da oncoproteína LMP1 do vírus de Epstein-Barr (EBV)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Lack of Epstein-Barr virus infection in cervical carcinomas

Context.-The Epstein-Barr virus (EBV) is a ubiquitous microorganism strongly associated with lymphoproliferative disorders and a large number of human neoplasms, mainly undifferentiated nasopharyngeal carcinoma and Burkitt lymphoma. The viral DNA has been detected in other tumors, such as carcinomas from tonsil, salivary glands, and thymus, and malignancies of the female genital tract. Some authors have proposed that EBV could play a role in the carcinogenesis of cervical tumors; however, other studies do not support this hypothesis.Objective.-To assess whether EBV is associated with female genital tract neoplasms.Design.-Sixty-five biopsy specimens (5 in situ carcinomas, 24 invasive squamous cell carcinomas, 6 lymphoepithelioma-like carcinomas, and 30 endocervical adenocarcinomas) were used to perform EBV detection through RNA in situ hybridization.Results.-None of the cervical carcinoma cases studied was positive for EBV infection.Conclusions.-The results suggest that it is still premature to incriminate EBV in the carcinogenesis of cervical carcinoma.

Geographic variation in Epstein-Barr virus-associated Burkitt's lymphoma in children from Brazil

In developing countries, BL has a strong association with EBV infection during childhood. In South America, the data have shown an EBV association intermediate between that reported in the United States (30%) and that in equatorial Africa (95%). Early age at EBV infection and lower socioeconomic status have been related to increased EBV-associated BL in developing countries. In Brazil, there are not enough data on childhood BL related to EBV infection. Our aim was to evaluate the clinicopathologic features and EBV association of 44 children with NHL from the state of Rio de Janeiro, situated in the southeast of Brazil. EBV was detected using RNA in situ hybridization in 36 biopsy specimens. DNA from fresh tumor samples and from paraffin-embedded tissues of patients were analyzed by PCR, in which the first reaction included primers for an EBNA-2 common region while the nested reaction amplified the region discriminating between EBV types I and 2 in separate reactions. EBV was detected in 21 of 29 BLs (72%), and type I virus infected the majority of EBV-positive BLs (18/21). There was a trend for younger age in children with EBV-positive BL compared to EBV-negative BL (median age 4 compared to 6 years, respectively; p = 0.056). Our study confirmed that in the southeast of Brazil BL had an intermediate association with EBV. A higher rate of EBV-associated BL was described in the northeast of Brazil. These differences are probably related to regional socioeconomic status. In conclusion, our study suggests that early infection with EBV in the background of a low socioeconomic condition associated with other environmental factors could contribute to BL in Brazil. (C) 2003 Wiley-Liss, Inc.

Epstein-Barr virus infection and gastric carcinoma in São Paulo State, Brazil

Epstein-Barr virus (EBV) is a ubiquitous herpesvirus, and most people have serological evidence of previous viral infection at adult age. EBV is associated with infectious mononucleosis and human cancers, including some lymphomas and gastric carcinomas. Although EBV was first reported in lymphoepithelioma-like gastric carcinoma, the virus was also found in conventional adenocarcinomas. In the present study, 53 gastric carcinomas diagnosed in São Paulo State, Brazil, were evaluated for EBV infection by non-isotopic in situ hybridization with a biotinylated probe (Biotin-AGACACCGTCCTCACCACCC GGGACTTGTA) directed to the viral transcript EBER-I, which is actively expressed in EBV latently infected cells. EBV infection was found in 6 of 53 (11.32%) gastric carcinomas, mostly from male patients (66.7%), with a mean age of 59 years old. Most EBV-positive tumors were in gastric antrum. Two EBV-positive tumors (33.3%) were conventional adenocarcinomas, whereas four (66.7%) were classified as lymphoepithelioma-like carcinomas. EBV infection in gastric carcinomas was reported elsewhere in frequencies that range from 5.6% (Korea) up to 18% (Germany). In Brazil, a previous work found EBV infection in 4 of 80 (5%) gastric carcinomas, whereas another study found 4.7 and 11.2% of EBV-positive gastric carcinomas of Brazilians of Japanese origin or not, respectively. In the present study, the frequency of EBV-positive gastric carcinomas is similar to that reported in other series, and the clinicopathologic characteristics of these EBV-positive tumors are in agreement with the data in the literature.

Epstein-Barr virus-associated gastric carcinoma in Brazil: comparison between in situ hybridization and polymerase chain reaction detection

Epstein-Barr virus (EBV) has been associated with 10% of gastric carcinomas. The aim of this study was to determine the frequency of EBV in gastric carcinomas in Brazil assessed by in situ hybridization (ISH) and PCR, which would contribute to the characterization of the clinical and pathological aspects of EBV-associated gastric carcinomas. One hundred and ninety-two gastric carcinoma cases were collected at hospitals in two Brazilian states. Seventy-three out of 151 cases were PCR(+), while 11/160 cases were ISH(+). Nine out of eleven ISH(+) cases displayed a diffuse staining pattern and 2 out of 11 a focal pattern. Both techniques showed that the EBV(+) cases were characterized by their association with males, older patients, lower gastric region, intestinal type, advanced stage and poorly to moderately differentiated tumors. The concordance between the two techniques was 55.8% (Cohen's kappa index = 0.034). Four cases were ISH(+)/PCR(-), while 49 cases were PCR(+)/ISH(-). Only two cases showed stained lymphocytes by ISH and one of them was PCR(-). The observed discrepancy between the two techniques could not be explained just by the elevated accuracy of PCR. ISH(+)/PCR(-) carcinomas may be encountered if EBV is not present in the whole tumor tissue or if there are polymorphisms in the sequences of the viral genome amplified. on the other hand, the high frequency of PCR(+) results associated with the absence of ISH staining in lymphocytes and/or tumors cells suggests that the virus may be present in tumor cells or other cell types without expressing EBER1, the target of the ISH technique.

Burkitt's lymphoma in Brazil: Strong association with Epstein-Barr virus

The incidence of Burkitt's lymphoma (BL) in Brazil is intermediate between the endemic form of equatorial Africa and the sporadic form in the United States, To characterize these lymphomas, we evaluated the clinical, morphologic, and immunohistochemical features of 24 Brazilian cases of BL, We also analyzed the cases for the presence of Epstein-Barr virus (EBV)-RNA using a highly sensitive and specific method of in situ hybridization, Most cases presented with involvement of intraabdominal organs, similar to the sporadic form of BL, EBV-RNA was detected in 17 of 24 cases (71%) in all or virtually all the tumor cells, This prevalence of EBV-positivity in our cases is intermediate between the endemic form of BL in equatorial Africa (100%) and the sporadic form in the United States (30%), These findings suggest that EBV plays an important role in the pathogenesis of BL in Brazil, This intermediate incidence of EBV infection may explain in part the differences of incidence of BL in different geographic regions.

AIDS-related lymphoma in Brazil - Histopathology, immunophenotype, and association with Epstein-Barr virus

The occurrence of malignant lymphoma is an increasingly important cause of morbidity and mortality in AIDS patients. The incidence of AIDS-related lymphoma in some developing countries such as Brazil is increasing as the survival of HIV infection has improved. Although there is a clear association between several types of immunodeficiency related lymphomas and Epstein-Barr virus (EBV), the association of EBV infection in AIDS-related lymphoma in Brazil, where the incidence of AIDS is high, is unknown. Formalin-fixed, paraffin-embedded tissue from 24 cases of AIDS-related lymphoma in Brazil were analyzed for morphologic classification, immunophenotype, and EBV association using in situ hybridization studies with an EBV-EBER1 biotinylated probe. Twenty cases of AIDS-related lymphoma were classified as non-Hodgkin's lymphoma and four cases were Hodgkin's disease. Eleven non-Hodgkin's lymphomas were classified as diffuse large cell type, five cases were small non-cleaved cell, Burkitt-type, and four cases were large cell immunoblastic non-Hodgkin's lymphoma. Eighteen cases were of B-cell phenotype; one was a T-cell lymphoma, and one was classified as null. Epstein-Barr virus (EBV) was demonstrated in the majority of tumor cells of 11 of 20 (55%) of the cases non-Hodgkin's lymphomas and in 3 of 4 (75%) cases of Hodgkin's disease. AIDS-related lymphomas in Brazil are usually of large cell/immunoblastic type, but Hodgkin's disease is also seen. Both non-Hodgkin's lymphoma and Hodgkin's disease are often associated with EBV infection. The non-Hodgkin's lymphoma is predominantly of B-cell phenotype.

Deletion of Epstein-Barr virus latent membrane protein 1 gene in United States and Brazilian Hodgkin's disease and reactive lymphoid tissue: High frequency of a 30-bp deletion

A 30-basepair (bp) deletion in the Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) gene has been reported in nasopharyngeal carcinoma and EBV-associated malignant lymphomas. Prior studies have found the deletion in about 10% to 28% of cases of Hodgkin's disease (HD), particularly in cases with aggressive histology. We studied the prevalence of 30-bp LMP1 gene deletion in EBV-positive HD in the United States (US) (12 cases) and Brazil (26 cases) with comparison to reactive lymphoid tissues (21 cases) and HD without EBV-positive Reed-Sternberg cells (15 cases). We studied the status of the LMP1 gene by Southern blot hybridization of polymerase chain reaction (PCR) products obtained after amplification with primers spanning the site of the deletion. We also performed EBV typing, EBER1 in situ hybridization, and LMP1 protein immunohistochemistry. EBV was detected in 12/26 (46%) cases of HD from the US and 26/27 (96%) cases of Brazilian HD. The 30-bp LMP1 gene deletion was observed in 4/12 (33%) cases of EBV-positive HD from US, and 12/26 (46%) cases of Brazilian EBV-positive HD, including 3 cases of type B EBV, as compared with 12/21 (57%) reactive lymphoid tissues and 9/15 (60%) cases of EBV-negative HD. US and Brazilian HD showed a higher prevalence of the 30-bp LMP1 gene deletion, compared with studies of others. The unexpected finding of high incidence of 30-bp deletion in LMP1 gene in reactive lymphoid tissue and HD without EBV-positive Reed-Sternberg cells suggests that this deletion may not be relevant to HD pathogenesis in most cases. Copyright (C) 1997 by W.B. Saunders Company.

Epstein-barr virus infection and single nucleotide Polymorphisms in the promoter region of interleukin 10 gene in patients with Hodgkin lymphoma

Context. - Hodgkin lymphoma is a neoplastic disease in which the immune system plays a major role in its pathogenesis. Interleukin 10 ( IL-10), an immunosuppressive cytokine actively produced in patients with Hodgkin lymphomas, favors the survival of the Hodgkin/Reed-Sternberg cells. Individual variations in IL-10 levels may be due, in part, to the presence of single nucleotide polymorphisms in the IL10 gene promoter.Objective. - To evaluate whether particular single nucleotide polymorphisms in the IL10 gene are found more frequently in Hodgkin lymphoma cases associated with Epstein-Barr virus infection.Design. - the identification of single nucleotide polymorphisms at positions -1082 and -819/-592 in the IL10 gene was performed by polymerase chain reaction and restriction length fragment polymorphisms analysis in 65 cases of Hodgkin lymphoma and 50 cases of reactive benign follicular lymphoid hyperplasia ( non-Hodgkin lymphoma control group).Results. - the frequency of the genotype GG at position -1082 was found to be significantly higher in patients with Epstein-Barr virus-positive Hodgkin lymphoma compared with Epstein-Barr virus-negative cases.Conclusions. - the results suggest that the presence of specific single nucleotide polymorphisms in the IL10 gene, notably those associated with high IL-10 production, may play a role in the susceptibility to Epstein-Barr virus -positive Hodgkin lymphoma development.