RESUMEN
Previous studies have investigated the prognostic relevance of MMP9 in classical Hodgkin lymphoma (cHL), with negative results. However, we have found that MMP9 immunoistochemical expression by Hodgkin-Reed-Sternberg cells is associated with reduced overall survival in a subset of young adult Brazilian patients diagnosed with cHL. Additionally, we have observed that MMP9 expression by neoplastic cells in cHL is associated with EBV positivity. These results may support a rational basis for additional studies on the role of this metalloproteinase as a target for therapy in classical Hodgkin lymphoma.
Asunto(s)
Enfermedad de Hodgkin/enzimología , Enfermedad de Hodgkin/patología , Metaloproteinasa 9 de la Matriz/metabolismo , Células de Reed-Sternberg/enzimología , Células de Reed-Sternberg/patología , Adolescente , Adulto , Femenino , Herpesvirus Humano 4/fisiología , Enfermedad de Hodgkin/virología , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Modelos de Riesgos Proporcionales , Células de Reed-Sternberg/virología , Análisis de Supervivencia , Adulto JovenRESUMEN
Clinical and histological features of classical Hodgkin lymphoma (cHL) are primarily due to the effects of cytokines and enzymes produced by Hodgkin/Reed-Sternberg (HRS) cells and their surrounding inflammatory cells. In EBV-related cancers, the expression of viral latent membrane protein 1 correlates with an increased MMP9 expression. In this study, we evaluated the prognostic relevance of MMP9 expression and EBV status in HRS cells in patients with cHL in Brazil. We selected 97 patients with cHL for EBV and MMP9 detection. EBV was detected in 52.5%, and MMP9 expression positivity was found in 87.6%. Of all cases, there was no correlation between MMP9 expression and EBV status. Response to treatment and relapse rate was independent of MMP9 expression and EBV status. MMP9 positivity did not influence overall survival and event-free survival. The consistent and increased intensity of MMP9 expression in HRS cells make this enzyme a potential target for therapy.
Asunto(s)
Enfermedad de Hodgkin/enzimología , Enfermedad de Hodgkin/mortalidad , Enfermedad de Hodgkin/virología , Metaloproteinasa 9 de la Matriz/biosíntesis , Células de Reed-Sternberg/enzimología , Adolescente , Adulto , Anciano , Brasil , Supervivencia sin Enfermedad , Infecciones por Virus de Epstein-Barr/complicaciones , Humanos , Estimación de Kaplan-Meier , Metaloproteinasa 9 de la Matriz/análisis , Persona de Mediana Edad , Adulto JovenRESUMEN
Hodgkin and Reed-Sternberg (H-RS) cells of classical Hodgkin lymphoma (cHL) present an impaired expression of immunoglobulin genes, but escape apoptotic death. We investigated whether nitric oxide synthases (NOS) are expressed by H-RS cells, studied their association with EBV status and the expression of apoptotic proteins, and investigated their relationship to the clinical outcome of 171 patients. NOS1 and NOS2 were expressed in a large number of cases, whereas NOS3 expression was not detected. Positive associations were found between NOS1 and p53, bax and NOS2, bcl-2 and NOS2, bax and p53, and between bax and fasL. Inverse correlations were established between EBV and NOS2 and between EBV and bcl-2. A shorter overall survival (OS) was associated with strong expression of NOS2. In conclusion, NOS are expressed by H-RS cells of cHL.