RESUMO
BACKGROUND: Plasmablastic lymphoma has recently come to be considered a distinct entity among mature B cell neoplasms, although the limits with diffuse large B-cell lymphoma (DLBCL) need to be more accurately defined. DESIGN AND METHODS: Here we show the results of an immunohistochemical study of 35 cases of plasmablastic lymphoma compared with a set of 111 conventional DLBCLs. RESULTS: Our results demonstrate that the use of a limited combination of immunohistochemical markers (PAX5&CD20, PRDM1/BLIMP1 and XBP1s) enables the identification of a plasmablastic immunophenotype highly characteristic of plasmablastic lymphoma cases and associated with an aggressive clinical behavior. Additionally, the study shows that the acquisition of a partial plasmablastic phenotype (PRDM1/BLIMP1 expression) in DLBCL is associated with shorter survival in R-CHOP-treated patients. CONCLUSIONS: The use of a restricted combination of immunohistochemical markers (PAX5&CD20, PRDM1/BLIMP1 and XBP1s) enables a more accurate definition of terminal differentiation for large B-cell lymphoma.
Assuntos
Linfoma de Células B/metabolismo , Linfoma Difuso de Grandes Células B/metabolismo , Plasmócitos/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD20/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Diferenciação Celular , Feminino , Humanos , Imuno-Histoquímica , Imunofenotipagem , Linfoma de Células B/tratamento farmacológico , Linfoma de Células B/patologia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fator de Transcrição PAX5/metabolismo , Plasmócitos/efeitos dos fármacos , Plasmócitos/patologia , Fator 1 de Ligação ao Domínio I Regulador Positivo , Proteínas Repressoras/metabolismo , Análise de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
Kv, which play a role in the immune system, are remodeled during carcinogenesis. Leukocytes present a limited Kv repertoire, with Kv1.3 and Kv1.5 as isoforms that are involved in neoplastic processes, such as proliferation and migration. In this study, we identified Kv1.5 in B-lymphocytes, characterized its role in proliferation and migration, and analyzed Kv1.3 and Kv1.5 expression in human non-Hodgkin lymphomas. DLBCL, F, MCL, ALCL, and T, along with control N specimens, were analyzed. Kv1.3 and Kv1.5 were found to be remodeled differentially; whereas Kv1.3 expression did not correlate with the state of dedifferentiation or the nature of lymphomatous cells, Kv1.5 abundance correlated inversely with clinical aggressiveness. Whereas indolent F expressed noticeable levels of Kv1.5, aggressive DLBCL showed low Kv1.5 levels. In addition, control LNs expressed heterogeneous high levels of Kv1.3, which could indicate some reactivity, whereas Kv1.5 abundance was low and quite homogeneous. Our data show that Kv1.5 is a determinant of human B cell proliferation and migration, thereby identifying this channel as a new target for immunomodulation. Our work also provides new insights into the use of Kv1.3 and Kv1.5 as potential targets during tumorigenesis.