RESUMO
Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma of the elderly was included as a provisional entity in the 2008 WHO lymphoma classification. Most reports of this disease come from Asia and little is known about it in other regions of the world, including Latin America. Therefore, in this study, 305 diffuse large B-cell lymphomas in patients above 50 years were analyzed, 136 from Mexico and 169 from Germany. EBV was detected by Epstein-Barr early RNA (EBER) in situ hybridization. Only cases with EBER+ in the majority of tumor cells were regarded as EBV+ diffuse large B-cell lymphoma. The prevalence of EBV+ diffuse large B-cell lymphoma in Mexican patients was found to be 7% (9 of 136), whereas only 2% (4 of 169) of the German cases were positive. The median age at diagnosis was 66 years in the Mexican cohort, as opposed to 77 years in the German group. The site of presentation was in both groups predominantly nodal in nine cases (70%) and extranodal in four cases (30%). Of the 13 EBV+ cases, 10 (77%) were classified as polymorphic and 3 (23%) as monomorphic type. The polymorphic cases showed a non-germinal center B-cell immunophenotype (CD10- MUM1+). Twelve cases (92%) were LMP1 positive and two (15%) expressed EBNA2. An interesting finding was the high frequency of EBV type B with the LMP1 30 bp deletion found in the Mexican cases (50%). Eight of the 11 evaluable cases were B-cell monoclonal by polymerase chain reaction. In summary, we found a similar prevalence of EBV+ diffuse large B-cell lymphoma of the elderly in a Mexican population compared with what has been reported in Asian countries, and in contrast to the low frequency in Western populations (1-3%). However, compared with the Asian series, the Mexican patients were younger at diagnosis, presented predominantly with nodal disease and rarely expressed EBNA2 protein.
Assuntos
Infecções por Vírus Epstein-Barr/epidemiologia , Infecções por Vírus Epstein-Barr/etiologia , Linfoma Difuso de Grandes Células B/epidemiologia , Linfoma Difuso de Grandes Células B/virologia , Idade de Início , Idoso , Infecções por Vírus Epstein-Barr/patologia , Antígenos Nucleares do Vírus Epstein-Barr/análise , Antígenos Nucleares do Vírus Epstein-Barr/biossíntese , Feminino , Alemanha/epidemiologia , Herpesvirus Humano 4/genética , Humanos , Hibridização In Situ , Linfoma Difuso de Grandes Células B/patologia , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Prevalência , Proteínas da Matriz Viral/análise , Proteínas da Matriz Viral/biossíntese , Proteínas Virais/análise , Proteínas Virais/biossínteseRESUMO
BACKGROUND: Pediatric nasopharyngeal carcinoma (NPC) is relatively rare. The Epstein Barr virus (EBV) association with the oncogenesis of NPC is well established. Apoptosis-related proteins, p53 and bcl-2, have also been described in adult NPC pathogenesis. PROCEDURE: From 1988 to 1998, 16 patients with NPC were treated at R. Gutierrez Children's Hospital and the National J.P. Garrahan Pediatric Hospital. Their median age was 12 years (range 8-20), 2 females and 14 males. The presence of p53, bcl-2 and latent membrane protein-1 (LMP-1) of EBV expression was studied by immunohistochemistry and Epstein Barr encoded RNAs (EBERs) by in situ hybridization in tissue sections from formalin-fixed, paraffin-embedded NPC biopsies RESULTS: EBV presence and LMP-1 expression in epithelial tumor cells were detected in all the biopsies studied. p53 was expressed in 13/16 NPCs, but the frequency of positive malignant cells differed from case to case, ranging from less than 25 to 100% with heterogeneous staining intensity. Bcl-2 positive staining in tumor epithelial cells was detected in 2/16; whereas 10/16 cases showed bcl-2 positivity in infiltrating lymphocytes. CONCLUSIONS: Although our series is small, we conclude that the pathogenesis of pediatric NPC as a multistep process may well involve EBV infection. This leads to LMP-1 expression and p53 overexpression in epithelial tumor cells, whereas bc-2 seems unrelated to the development of this disorder.
Assuntos
Carcinoma/genética , Carcinoma/virologia , DNA de Neoplasias/genética , Infecções por Vírus Epstein-Barr/complicações , Regulação Neoplásica da Expressão Gênica , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/virologia , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Proteína Supressora de Tumor p53/biossíntese , Proteínas da Matriz Viral/biossíntese , Adolescente , Adulto , Criança , Feminino , Humanos , Imuno-Histoquímica , Hibridização In Situ , Masculino , RNARESUMO
A live virus vaccine vector has been constructed from a molecularly cloned attenuated strain of Venezuelan equine encephalitis virus (VEE). High levels of foreign protein expression are regulated by an additional copy of the 26 S viral subgenomic RNA promoter. The position of this additional promoter and foreign gene in the VEE genome was predicted to have a major influence on expression level of the heterologous protein. Two sites in the genome were tested to determine the optimal site for expression of the matrix/capsid (MA/CA) coding region of human immunodeficiency virus (HIV-1). One vector contained the additional promoter and the MA/CA genes immediately downstream of the VEE E1 gene at the 3' end of the genome. In the second vector, the additional promoter was introduced immediately upstream from the authentic 26 S subgenomic promoter. Significantly higher levels of MA/CA were expressed from the downstream vector compared to the upstream vector. However, the stability of expression for both vectors was similar following passage in baby hamster kidney cells (BHK) cells. In BALB/c mice, the two vectors elicited similar levels of cellular immune responses to MA/CA as determined by bulk cytotoxic T-lymphocyte assays and precursor frequency analysis, but the humoral response induced by the downstream vector was significantly stronger. At 11 months post boosting with the downstream vector, serum antibody levels against HIV MA/CA were undiminished, and MA/CA specific CTLp were detectable in all mice tested. These findings suggest that VEE vectors can be optimized to elicit strong, balanced and long-lived immune responses to foreign viral proteins.
Assuntos
Vacinas contra a AIDS/genética , Vírus da Encefalite Equina Venezuelana/genética , Vírus da Encefalite Equina Venezuelana/imunologia , Vetores Genéticos/síntese química , Vetores Genéticos/imunologia , HIV-1/genética , Vacinas de DNA/genética , Vacinas contra a AIDS/imunologia , Animais , Capsídeo/biossíntese , Capsídeo/genética , Capsídeo/imunologia , Células Cultivadas , Cricetinae , Feminino , Genoma Viral , Anticorpos Anti-HIV/biossíntese , Anticorpos Anti-HIV/sangue , HIV-1/imunologia , Humanos , Ativação Linfocitária/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Regiões Promotoras Genéticas/imunologia , Células-Tronco/imunologia , Linfócitos T Citotóxicos/imunologia , Proteínas da Matriz Viral/biossíntese , Proteínas da Matriz Viral/genética , Proteínas da Matriz Viral/imunologiaRESUMO
The Epstein-Barr Virus (EBV) is consistently found in tumor cells of Burkitt's lymphoma (BL) endemic in central Africa and malaria is considered a pathogenic cofactor. In contrast, fewer than 20% of BL cases occurring in Western countries are EBV-associated. We have investigated 54 BL cases from Bahia, a tropical region of Northeast Brazil, for expression of EBV gene products by in situ hybridization and immunohistology and performed typing of the EBV by polymerase chain reaction. Ten pediatric BL cases from Germany served as controls. New cases of malaria were not observed in the period and area of our study. Small nuclear EBV encoded transcripts, EBER, were found in tumor cells of 47 of 54 Brazilian cases (87%) but in only 2 of 10 German cases (20%). Type I latency of the EBV infection with absence of EBV-encoded proteins LMP1 and EBNA2 was found in 45 of 47 of the EBER-positive Brazilian cases. In two cases, occasional LMP1-containing tumor cells were found in the neighborhood of small Schistosoma mansoni granulomas and scars. BHLF1 transcripts associated with lytic EBV infection could be detected in few cells in 3 of the 40 EBER-positive Brazilian cases investigated. EBV type A was found in the majority of Brazilian BL cases (20 of 30 A-type, 7 of 30 B-type, and 3 of 30 not amplifiable). Our results indicate that the association of Bahian BL with EBV, but not the regional prevalence of malaria, is similar to endemic African BL. In two cases, type II latency was found in association with schistosomiasis, suggesting a role of this parasitosis in the induction of an EBV expression pattern that is unusual for BL. Because chronic schistosomiasis is associated with elevated Th2 cytokine expression resulting in reduced cell-mediated cytotoxicity, it seems possible that altered local immunity is responsible for this peculiar phenotype.