Investigação de novos alvos imunofenotípicos aplicados ao diagnóstico de neoplasias de células linfoides B maduras

Tese (doutorado) - Universidade Federal de Santa Catarina, Centro de Ciências da Saúde, Programa de Pós-Graduação em Farmácia, Florianópolis, 2017.

Nível de Acesso:openAccess
Publication Date:2017
Main Author: Oliveira, Renata Cristina Messores Rudolf de
Orientador/a: Silva, Maria Cláudia Santos da
Format: Tese
Online Access:
Resumo inglês:Abstract : The diagnosis of mature B-cell neoplasms (MBCN) is based on the combination of clinical, morphological, genetic and immunophenotypic information. In recent years, the interest for methods such as immunophenotyping by flow cytometry has increased because this methodology is able to provide fast and important information about the patients diagnosis. However, there are some situations in which the overlapping of cellular phenotypic characteristics hampers the diagnosis, thus it cannot be properly concluded. Therefore, the investigation of immunophenotypic markers is necessary so that the differential diagnosis between some subtypes of MBCN can be performed. The aim of this study was to investigate immunophenotypic targets (CD80, CD86, CD163, CD261, CD261, CD262, CD264, CD358 and CD361) possibly applicable as markers for the differential diagnosis of MBCN, and also targets possibly useful for prognosis (survivin, ABCB1/PgP and ABCC1/MRP1). Bone marrow (BM) and peripheral blood (PB) samples were used to characterize the markers in non-neoplastic cells. In neoplastic cells, 195 samples from MBCN patients were used. CD80 was heterogeneously expressed in MBCN. CD86 expression was moderate in the neoplastic cells of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma, and weak in the cells of Burkitt lymphoma, chronic lymphocytic leukemia (CLL), lymphoplasmacytic lymphoma, marginal zone lymphoma and multiple myeloma (MM). CD361 expression differentiated MM from other MBCN. There was no difference in ABCC1/MRP1 and ABCB1/PgP protein expression among the MBCN. Survivin was expressed in all MBCN with some differences among then and overexpression was observed in CML, MM, B-cell lymphoma CD5 and CD10 negative and DLBCL neoplastic cells. Among the neoplasms, CD261 expression was significantly different in MM when compared to all MBCN. In addition, the results showed that non-neoplastic plasma cells express CD261, while clonal plasma cells do not express this marker. Thus, CD261 expression can be used as an auxiliary tool in the immunophenotypic diagnosis of MM. CD262 was useful in the differential diagnosis between neoplasms requiring distinction due to phenotypic overlap. This marker allows the differentiation between CD10 negative DLBCL cases with mantle cell lymphoma (MCL) and cases of CD10 negative DLBCL and CLL. Thus, the most useful marker in the differential diagnosis of MBCN was CD262, while CD261 was the most efficient market to differentiate normal and neoplastic cells. As a result, these markers can be used as an auxiliary tool in the immunophenotypic diagnosis of MBCN.