RESUMEN
Simian virus 40 (SV40) is associated with some systemic non-Hodgkin's lymphomas (NHL) among HIV-positive patients, based on assays for viral DNA sequences. To investigate the possible production of the viral transforming protein, we examined age-matched case-control specimens from patients with HIV/AIDS for the expression of SV40 large tumor antigen (T-ag). Masked specimens initially examined by polymerase chain reaction (PCR) for polyomavirus and herpesvirus DNA sequences were assessed for the expression of SV40 T-ag and phenotypic lymphocyte markers by immunohistochemistry (IHC). Fifty-five systemic NHL and 25 nonmalignant lymphoid and malignant nonlymphoid tissue control cases from two HIV community programs in Texas and New Jersey were scored for IHC positivity without knowledge of the PCR results. IHC showed expression of SV40 T-ag among B-cell lymphomas, whereas none of the control tissue samples were positive for T-ag (12/55, 22% vs. 0/25, 0%; P = 0.01). SV40 T-ag expression was detected only in B-cell lymphoma specimens that contained SV40 DNA sequences. Not all lymphoma cells in a positive specimen stained for T-ag, and the reaction was lower intensity than observed in SV40 hamster tumors. SV40 T-ag was demonstrated in both primary and recurrent tumors from one patient. A germinal center B-cell-like (GCB) profile was more frequently expressed by SV40-positive tumors than in Epstein-Barr virus (EBV)-related lymphomas (10/12, 83% vs. 6/13, 46%; P = 0.05), whereas a non-GCB phenotype was more frequent in EBV-positive than in SV40-positive lymphomas (7/13, 54% vs. 2/12, 17%; P = 0.05). This study shows that SV40 gene expression occurs in a fraction of cells in some B-cell lymphomas among patients with HIV/AIDS.
Asunto(s)
Antígenos Transformadores de Poliomavirus/genética , Linfoma Relacionado con SIDA/inmunología , Linfoma Relacionado con SIDA/virología , Linfoma no Hodgkin/inmunología , Linfoma no Hodgkin/virología , Adulto , Secuencia de Bases , Estudios de Casos y Controles , ADN Viral/genética , ADN Viral/aislamiento & purificación , Femenino , Expresión Génica , Genes Virales , VIH-1 , Humanos , Inmunofenotipificación , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Recurrencia Local de Neoplasia/inmunología , Recurrencia Local de Neoplasia/virología , Virus 40 de los Simios/genética , Virus 40 de los Simios/aislamiento & purificaciónRESUMEN
Plasmablastic lymphoma is an aggressive neoplasm that shares many cytomorphologic and immunophenotypic features with plasmablastic plasma cell myeloma. However, plasmablastic lymphoma is listed in the World Health Organization (WHO) classification as a variant of diffuse large B-cell lymphoma. To characterize the relationship between plasmablastic lymphoma and plasmablastic plasma cell myeloma, we performed immunohistochemistry using a large panel of B-cell and plasma cell markers on nine cases of plasmablastic lymphoma and seven cases of plasmablastic plasma cell myeloma with and without HIV/AIDS. The expression profiles of the tumor suppressor genes p53, p16, and p27, and the presence of Epstein-Barr virus (EBV) and human herpes virus type 8 (HHV-8) were also analyzed. All cases of plasmablastic lymphoma and plasmablastic plasma cell myeloma were positive for MUM1/IRF4, CD138, and CD38, and negative for CD20, corresponding to a plasma cell immunophenotype. PAX-5 and BCL-6 were weakly positive in 2/9 and 1/5 plasmablastic lymphomas, and negative in all plasmablastic plasma cell myelomas. Three markers that are often aberrantly expressed in cases of plasma cell myelomas, CD56, CD4 and CD10, were positive in 5/9, 2/5, and 6/9 plasmablastic lymphomas, and in 3/7, 1/5, and 2/7 plasmablastic plasma cell myelomas. A high Ki-67 proliferation index, overexpression of p53, and loss of expression of p16 and p27 were present in both tumors. No evidence of HHV-8 infection was detected in either neoplasm. The only significant difference between plasmablastic lymphoma and plasma cell myeloma was the presence of EBV-encoded RNA, which was positive in all plasmablastic lymphoma cases tested and negative in all plasma cell myelomas. In conclusion, most cases of AIDS-related plasmablastic lymphoma have an immunophenotype and tumor suppressor gene expression profile virtually identical to plasmablastic plasma cell myeloma, and unlike diffuse large B-cell lymphoma. These results do not support the suggestion in the WHO classification that plasmablastic lymphoma is a variant of diffuse large B-cell lymphoma.
Asunto(s)
Inmunofenotipificación , Linfoma/patología , Mieloma Múltiple/patología , Células Plasmáticas/patología , Adulto , Anciano , Antígenos CD/análisis , ADN Viral/genética , Proteínas de Unión al ADN/análisis , Infecciones por Virus de Epstein-Barr/inmunología , Infecciones por Virus de Epstein-Barr/patología , Infecciones por Virus de Epstein-Barr/virología , Femenino , Herpesvirus Humano 4/genética , Herpesvirus Humano 8/genética , Humanos , Inmunohistoquímica , Hibridación in Situ , Antígeno Ki-67/análisis , Linfoma/inmunología , Linfoma/virología , Linfoma Relacionado con SIDA/inmunología , Linfoma Relacionado con SIDA/patología , Linfoma Relacionado con SIDA/virología , Masculino , Persona de Mediana Edad , Mieloma Múltiple/inmunología , Mieloma Múltiple/virología , Células Plasmáticas/inmunología , Células Plasmáticas/virología , Reacción en Cadena de la Polimerasa , Proteínas Proto-Oncogénicas/análisis , Proteínas Proto-Oncogénicas c-bcl-2/análisis , Proteínas Proto-Oncogénicas c-bcl-6 , Factores de Transcripción/análisis , Proteína p53 Supresora de Tumor/análisisRESUMEN
Studies conducted before the introduction of highly active antiretroviral therapy (HAART) suggested that the risk of Hodgkin lymphoma in persons with human immunodeficiency virus (HIV) infection was increased. However, little is known about the features of this malignancy in patients receiving HAART. From January 1996 through December 2001, 23 cases of Hodgkin lymphoma were diagnosed among 3,945 HIV infected patients attending the Harris County Hospital District in Houston, Texas. Twenty (87%) of the HIV-infected patients diagnosed with Hodgkin lymphoma were receiving HAART and 3 (13%) were naive to antiretroviral therapy. The incidence per 1,000 patients of Hodgkin lymphoma in patients receiving HAART was 6.5. The median duration of HAART before the diagnosis of Hodgkin lymphoma was 16 months (range, 7-22 mo). The median CD4 cell count was 235 cells/mm(3) (range, 189-325 cells/mm(3)) for the 20 HIV-infected patients receiving HAART at the time of diagnosis of Hodgkin lymphoma and 90 cells/mm (range, 72-120 cells/mm(3)) for the 3 patients naive for antiretroviral therapy. Among patients with Hodgkin lymphoma receiving HAART, 50% (10/20) had an HIV-RNA viral load in plasma below the level of detection <400 copies/mL). Chemotherapy was administered to all patients, but a complete response was achieved in 30% (6/20) of the patients receiving HAART and 0% (0/3) of the patients naive to antiretroviral therapy. These results suggest that Hodgkin lymphoma has a low incidence in HIV-infected patients receiving HAART, but the malignancy is an aggressive disease with unfavorable clinical outcome in these patients.
Asunto(s)
Terapia Antirretroviral Altamente Activa , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Enfermedad de Hodgkin/epidemiología , Linfoma Relacionado con SIDA/epidemiología , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Recuento de Linfocito CD4 , Inhibidores de la Proteasa del VIH/uso terapéutico , VIH-1/genética , VIH-1/aislamiento & purificación , Humanos , Incidencia , Linfoma Relacionado con SIDA/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , ARN Viral/análisis , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Texas/epidemiología , Factores de Tiempo , Resultado del Tratamiento , Carga ViralRESUMEN
BACKGROUND: Non-Hodgkin lymphoma has increased in frequency over the past 30 years, and is a common cancer in HIV-1-infected patients. Although no definite risk factors have emerged, a viral cause has been postulated. Polyomaviruses are known to infect human beings and to induce tumours in laboratory animals. We aimed to identify which one of the three polyomaviruses able to infect human beings (simian virus 40 [SV40], JC virus, and BK virus) was associated with non-Hodgkin lymphoma. METHODS: We analysed systemic non-Hodgkin lymphoma from 76 HIV-1-infected and 78 HIV-1-uninfected patients, and non-malignant lymphoid samples from 79 HIV-1-positive and 107 HIV-1-negative patients without tumours; 54 colon and breast carcinoma samples served as cancer controls. We used PCR followed by Southern blot hybridisation and DNA sequence analysis to detect DNAs of polyomaviruses and herpesviruses. FINDINGS: Polyomavirus T antigen sequences, all of which were SV40-specific, were detected in 64 (42%) of 154 non-Hodgkin lymphomas, none of 186 non-malignant lymphoid samples, and none of 54 control cancers. This difference was similar for HIV-1-infected patients and HIV-1-uninfected patients alike. Few tumours were positive for both SV40 and Epstein-Barr virus. Human herpesvirus type 8 was not detected. SV40 sequences were found most frequently in diffuse large B-cell and follicular-type lymphomas. INTERPRETATION: SV40 is significantly associated with some types of non-Hodgkin lymphoma. These results add lymphomas to the types of human cancers associated with SV40.