RESUMO
Diffuse large B-cell lymphoma can be classified into two prognostically distinct subgroups with germinal center B-cell-like (CG) and activated B-cell-like (post-CG) characteristics, based on CD10, BCL-6, and MUM1 expression. We performed a retrospective analysis of the clinical variables of 37 patients with primary mediastinal large B-cell lymphoma and the expression of BCL-6 and MUM1 in 22 patients with available tissue. The median age was 30 years, and 70% of the patients were female. BCL-6 and MUM1 were expressed in 64% and 45% of cases, respectively. Five-year overall survival (OS) and disease-free survival (DFS) were 47% and 81%, respectively. In univariate analysis, complete response (pâ=â0.0001), radiation therapy (pâ=â0.01), International Prognostic Index (pâ=â0.001), and MUM1 expression (pâ=â0.002) correlated with OS. For this group of patients with homogeneous clinical characteristics, response to initial chemotherapy and MUM1 expression were associated with prognosis.
Assuntos
Proteínas de Ligação a DNA/biossíntese , Fatores Reguladores de Interferon/biossíntese , Linfoma Difuso de Grandes Células B/metabolismo , Neoplasias do Mediastino/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Biomarcadores Tumorais/biossíntese , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/terapia , Masculino , Neoplasias do Mediastino/patologia , Neoplasias do Mediastino/terapia , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Prognóstico , Modelos de Riscos Proporcionais , Proteínas Proto-Oncogênicas c-bcl-6 , Estudos Retrospectivos , Adulto JovemRESUMO
Burkitt lymphoma is a highly aggressive non-Hodgkin lymphoma with endemic, sporadic, and immunodeficiency-associated clinical variants composed of monomorphic medium-sized B cells with a high proliferation rate and a translocation involving the C-MYC locus. Classically, the immunophenotype of Burkitt lymphoma has been considered to be the germinal center type. In most reports, all cases of Burkitt lymphoma are reported to be multiple myeloma 1-negative. multiple myeloma 1 expression is seen in plasma cells and in a small fraction of B cells located in the light zone of germinal centers corresponding to the final step of intra-germinal center B-cell differentiation, and in activated T cells. Therefore, multiple myeloma 1 expression may denote the final step of intra-germinal center B-cell differentiation at the centrocyte stage, as well as the subsequent steps of B-cell maturation toward plasma cells. Unlike most normal germinal center B cells, in which the expression of multiple myeloma 1 and bcl-6 are mutually exclusive, the tumor cells in approximately 50% of multiple myeloma 1-positive DLBCL show coexpression of bcl-6, suggesting that the expression of these proteins may be deregulated. Twenty-five Burkitt lymphoma cases, including 19 associated with HIV, were reported in one of the few studies in the literature; 2 of these cases showed occasional multiple myeloma 1-positive cells, less than the 20% cutoff for positivity. We studied 222 cases of well-characterized Burkitt lymphoma with the classic phenotype and C-MYC translocation and found 90 cases (40.5%) with multiple myeloma 1 nuclear expression, suggesting a late germinal center stage of differentiation.
Assuntos
Linfoma de Burkitt/metabolismo , Linfoma de Burkitt/patologia , Fatores Reguladores de Interferon/biossíntese , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfoma de Burkitt/genética , Diferenciação Celular/fisiologia , Criança , Pré-Escolar , Proteínas de Ligação a DNA/biossíntese , Feminino , Centro Germinativo/patologia , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Lactente , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-bcl-6 , Estudos Retrospectivos , Sindecana-1/biossíntese , Análise Serial de TecidosRESUMO
Non-syndromic cleft lip with or without cleft palate (NSCLP) results from the complex interaction between genes and environmental factors. Candidate gene analysis and genome scans have been employed to identify the genes contributing to NSCLP. In this study, we evaluated the 16q24.1 chromosomal region, which has been identified by multiple genome scans as an NSCLP region of interest. Two candidate genes were found in the region: interferon regulatory factor 8 (IRF8) and cysteine-rich secretory protein LCCL domain containing 2 (CRISPLD2). Initially, Caucasian and Hispanic NSCLP multiplex families and simplex parent-child trios were genotyped for single nucleotide polymorphisms (SNPs) in both IRF8 and CRISPLD2. CRISPLD2 was subsequently genotyped in a data set comprised of NSCLP families from Colombia, South America. Linkage disequilibrium analysis identified a significant association between CRISPLD2 and NSCLP in both our Caucasian and Hispanic NSCLP cohorts. SNP rs1546124 and haplotypes between rs1546124 and either rs4783099 or rs16974880 were significant in the Caucasian multiplex population (P=0.01, P=0.002 and P=0.001, respectively). An altered transmission of CRISPLD2 SNPs rs8061351 (P=0.02) and rs2326398 (P=0.06) was detected in the Hispanic population. No association was found between CRISPLD2 and our Colombian population or IRF8 and NSCLP. In situ hybridization showed that CRISPLD2 is expressed in the mandible, palate and nasopharynx regions during craniofacial development at E13.5-E17.5, respectively. Altogether, these data suggest that genetic variation in CRISPLD2 has a role in the etiology of NSCLP.