Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 12 de 12
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
J Clin Exp Hematop ; 59(1): 1-16, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30918139

RESUMO

The microenvironment influences the behavior of follicular lymphoma (FL) but the specific roles of the immunomodulatory BTLA and TNFRSF14 (HVEM) are unknown. Therefore, we examined their immunohistochemical expression in the intrafollicular, interfollicular and total histological compartments in 106 FL cases (57M/49F; median age 57-years), and in nine relapsed-FL with transformation to DLBCL (tFL). BTLA expression pattern was of follicular T-helper cells (TFH) in the intrafollicular and of T-cells in the interfollicular compartments. The mantle zones were BTLA+ in 35.6% of the cases with similar distribution of IgD. TNFRSF14 expression pattern was of neoplastic B lymphocytes (centroblasts) and "tingible body macrophages". At diagnosis, the averages of total BTLA and TNFRSF14-positive cells were 19.2%±12.4STD (range, 0.6%-58.2%) and 46.7 cells/HPF (1-286.5), respectively. No differences were seen between low-grade vs. high-grade FL but tFL was characterized by low BTLA and high TNFRSF14 expression. High BTLA correlated with good overall survival (OS) (total-BTLA, Hazard Risk=0.479, P=0.022) and with high PD-1 and FOXP3+Tregs. High TNFRSF14 correlated with poor OS and progression-free survival (PFS) (total-TNFRSF14, HR=3.9 and 3.2, respectively, P<0.0001), with unfavorable clinical variables and higher risk of transformation (OR=5.3). Multivariate analysis including BTLA, TNFRSF14 and FLIPI showed that TNFRSF14 and FLIPI maintained prognostic value for OS and TNFRSF14 for PFS. In the GSE16131 FL series, high TNFRSF14 gene expression correlated with worse prognosis and GSEA showed that NFkB pathway was associated with the "High-TNFRSF14/dead-phenotype".In conclusion, the BTLA-TNFRSF14 immune modulation pathway seems to play a role in the pathobiology and prognosis of FL.


Assuntos
Linfoma Folicular/diagnóstico , Linfoma Difuso de Grandes Células B/diagnóstico , Receptores Imunológicos/metabolismo , Membro 14 de Receptores do Fator de Necrose Tumoral/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos B/química , Linfócitos B/patologia , Transformação Celular Neoplásica , Feminino , Humanos , Fatores Imunológicos , Linfoma Folicular/mortalidade , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de Sobrevida , Linfócitos T/química
4.
J Clin Exp Hematop ; 57(2): 54-63, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29021515

RESUMO

The estimation of clinical prognosis for diffuse large B-cell lymphoma (DLBCL) with a quick, cost-efficient method is necessary because of the clinical heterogeneity of this disease, which leads to death, relapsed or refractory disease in approximately 40% of patients. We analyzed 320 cases diagnosed from 2007 to 2013 treated with R-CHOP therapy at Tokai University Hospital and associated institutions. DLBCL was classified according to the cell-of-origin using the Hans algorithm [germinal center B-cell-like (GCB) vs non-GCB subtypes], and into 6 subgroups derived from combinations of CD10, BCL6 and MUM1 markers. The percentage of GCB and non-GCB (NGCB) subtypes was 35% and 65%, respectively. GCB-DLBCL was characterized by lower BCL2 immunohistochemical expression, extranodal sites <1, better therapeutic response, and favorable overall survival (OS) and progression free survival (PFS) (P<0.01). The most frequent subgroup was NGCB-1 (CD10-BCL6+MUM1+, 51%) followed by GCB-1 (CD10+BCL6+or-MUM1+, 21%), NGCB-2 (CD10-BCL6-MUM1+, 13%), GCB-2 (CD10+BCL6+or-MUM1-, 10%), GCB-3 (CD10-BCL6+MUM1-, 4%) and NGCB-3 (CD10-BCL6-MUM1-, 2%). In comparison with GCB-2 and GCB-3 (both MUM1-), the GCB-1 (MUM1+) was characterized by favorable PFS (5-year PFS 84% vs 65%, OR 0.368, P<0.05), independent of high LDH (associated with unfavorable PFS, OR 7.04, P<0.01) in the multivariate analysis. This predictive value of MUM1 was independent of CD10. Interestingly, triple-negative NGCB-3 tended to have a more favorable prognosis than the other NGCB subgroups. In conclusion, the Hans classifier is a valid method to evaluate the prognosis of DLBCL NOS. In the GCB subtypes, GCB subtypes, MUM1-positivity is associated with a more favorable outcome (PFS).


Assuntos
Algoritmos , Antígenos de Diferenciação/sangue , Antígenos de Neoplasias/sangue , Biomarcadores Tumorais/sangue , Linfoma Difuso de Grandes Células B , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Linfoma Difuso de Grandes Células B/sangue , Linfoma Difuso de Grandes Células B/classificação , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida
5.
Am J Surg Pathol ; 40(8): 1041-50, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27158755

RESUMO

Angioimmunoblastic T-cell lymphoma (AITL) is an infrequent subtype of peripheral T-cell lymphoma derived from follicular helper T cells. Recently, a somatic G17V RHOA gene mutation has been reported. In this article, we examined the RHOA G17V mutation in 18 cases of AITL by 3 different techniques of Sanger sequencing, fully automated SNP genotyping, and deep sequencing, using routine diagnostic formalin-fixed paraffin-embedded tissue. The RHOA G17V mutation was detected in 10 cases (56%). Among the 10 mutated cases, 8 cases were detected by all 3 methods. The status of RHOA mutation was subsequently compared with the clinicopathologic characteristics of AITL. RHOA-mutated AITL (10 cases) was clinically characterized by high serum IL-2R and a poor ECOG performance status. By immunohistochemistry, expression of CD10, PD-1, CXCL13, and CCR4 and a wide distribution of CD21(+) follicular dendritic cells were observed in RHOA-mutated cases. Among these, CCR4 expression and the CD21(+) network in RHOA-mutated AITL cases were more extensive than in the RHOA mutation-negative AITL cases (P<0.05). Thus, RHOA-mutated AITL cases are more characteristic of follicular helper T cells, and the presence of such a mutation is an important marker for AITL.


Assuntos
Análise Mutacional de DNA/métodos , Linfoma de Células T/genética , Proteína rhoA de Ligação ao GTP/genética , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Feminino , Citometria de Fluxo , Formaldeído , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Linfadenopatia Imunoblástica/genética , Linfadenopatia Imunoblástica/patologia , Imuno-Histoquímica , Hibridização In Situ , Linfoma de Células T/patologia , Masculino , Pessoa de Meia-Idade , Inclusão em Parafina , Reação em Cadeia da Polimerase , Fixação de Tecidos
6.
Am J Surg Pathol ; 40(3): 324-34, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26752547

RESUMO

Primary breast diffuse large B-cell lymphoma (PB-DLBCL) is a rare disease comprising <3% of extranodal lymphomas. It frequently reveals an activated B-cell (ABC)-like phenotype. ABC-like DLBCL was reported to have gain-of-function mutations in MYD88, CD79B, CARD11, and TNFAIP3, resulting in constitutive activation of the NFκB pathway. Because of the rare occurrence of PB-DLBCL, the frequency of MYD88 and CD79B mutations is still unknown. We used Sanger sequencing to study these mutations from 46 breast DLBCL cases and also investigated the associated clinicopathologic factors. MYD88 L265P was confirmed by allele-specific polymerase chain reaction and compared with the Sanger sequencing results. MYD88 L265P and CD79B mutations were detected in 27/46 (58.7%) and 11/33 (33.3%) cases, respectively. Twenty-eight of 46 cases met the criteria for PB-DLBCL, and the latter 18 cases were further classified as clinical breast DLBCL (CLB-DLBCL). The frequency of MYD88 L265P and CD79B mutations was 16/28 (57.1%) and 9/23 (39.1%), respectively, in PB-DLBCL and 11/18 (61.1%) and 2/10 (20%), respectively, in CLB-DLBCL. When the cutoff value was set at ΔCt≤1, the result of allele-specific polymerase chain reaction for MYD88 corresponded to those of the Sanger sequence at 92.6% sensitivity and 100% specificity. According to Choi's algorithm, 16/27 (59.3%) demonstrated an ABC-like phenotype in PB-DLBCL, and 15/18 (83.3%) demonstrated an ABC-like phenotype in CLB-DLBCL. In conclusion, MYD88 L265P and CD79B mutations were frequently detected in PB-DLBCL, and they may be key molecules associated with PB-DLBCL lymphomagenesis. Further analysis will be required to clarify the mechanism of its pathogenesis.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Antígenos CD79/genética , Linfoma Difuso de Grandes Células B/genética , Mutação , Fator 88 de Diferenciação Mieloide/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Biomarcadores Tumorais/análise , Neoplasias da Mama/química , Neoplasias da Mama/patologia , Análise Mutacional de DNA , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Imuno-Histoquímica , Hibridização In Situ , Japão , Linfoma Difuso de Grandes Células B/química , Linfoma Difuso de Grandes Células B/patologia , Pessoa de Meia-Idade , Fenótipo , Reação em Cadeia da Polimerase , Valor Preditivo dos Testes , Prognóstico , Taiwan
7.
Int J Hematol ; 101(5): 520-4, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25555480

RESUMO

We report a case of HIV-negative Burkitt lymphoma (BL) that relapsed 9 years after complete remission. We performed a polymerase chain reaction analysis of three regions of the VDJ junction of the immunoglobulin heavy chain (IGH) gene and compared the clonality of the first and second BL lesions, which were found to be clonally distinct. The patient received the R-Hyper CVAD/R-MA regimen; however, leukoencephalopathy subsequently developed due to the effect of cytarabine, and the regimen was changed to R-IVAM. The patient achieved complete remission and received high-dose chemotherapy following autologous stem cell transplantation. He maintained the complete remission for 72 months after transplantation. Given this outcome, we suggest that clonally distinct relapse of HIV-negative BL may exhibit a good prognosis.


Assuntos
Linfoma de Burkitt/genética , Linfoma de Burkitt/terapia , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/terapia , Recombinação V(D)J , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Sequência de Bases , Linfoma de Burkitt/patologia , Ciclofosfamida/uso terapêutico , Citarabina/uso terapêutico , Dexametasona/uso terapêutico , Doxorrubicina/uso terapêutico , Etoposídeo/uso terapêutico , Genes de Imunoglobulinas , Transplante de Células-Tronco Hematopoéticas , Humanos , Ifosfamida/uso terapêutico , Cadeias Pesadas de Imunoglobulinas/genética , Masculino , Metotrexato/uso terapêutico , Dados de Sequência Molecular , Recidiva Local de Neoplasia/patologia , Indução de Remissão , Vincristina/uso terapêutico
8.
Cancer Sci ; 105(9): 1170-5, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24974976

RESUMO

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of malignant lymphoma. The incidence of Epstein-Barr virus (EBV)-positive DLBCL in Asian and Latin American countries ranges from 8 to 10%. The prognosis of patients with EBV-positive DLBCL is controversial. To compare the clinical outcome of EBV-positive and EBV-negative patients with DLBCL in the rituximab era, we analyzed 239 patients with de novo DLBCL diagnosed between January 2007 and December 2011. The presence of EBV in lymphoma cells was detected using EBV-encoded RNA in situ hybridization, and it was found that 18 (6.9%) of 260 patients with diagnosed DLBCL tested positive. Among the 260 cases, 216 cases were treated with rituximab plus chemotherapy, as were 8 EBV-positive DLBCL patients. The median overall survival and progression-free survival times in patients with EBV-positive DLBCL were 8.7 months and 6.8 months, respectively. The median overall survival and progression-free survival could not be determined in EBV-negative DLBCL patients (P = 0.0002, P < 0.0001, respectively). The outcome of patients with EBV-positive DLBCL remains poor, even in the rituximab era.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Infecções por Vírus Epstein-Barr/complicações , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Idoso , Anticorpos Monoclonais Murinos/administração & dosagem , Anticorpos Monoclonais Murinos/uso terapêutico , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Infecções por Vírus Epstein-Barr/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/virologia , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Modelos de Riscos Proporcionais , Rituximab , Resultado do Tratamento , Vincristina/uso terapêutico
10.
Pathol Int ; 63(7): 339-44, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23865571

RESUMO

The basic region-leucine zipper (bZip) factor BTB, CNC homology 2 (BACH2) is known to have important roles in class switch recombination and somatic hypermutation (SHM) of the immunoglobulin (Ig) gene. In this study, we investigated the relationship between the expression of BACH2 and the status of SHM of the Ig heavy chain gene variable region (IgHV) for SHM in diffuse large B-cell lymphoma (DLBCL). We examined 20 cases of DLBCL, 13 of which were germinal center B-cell (GCB) DLBCL and 7 were non-GCB DLBCL. Seven cases were negative, 6 were positive (cytoplasmic expression) and 7 were strongly positive (both nuclear and cytoplasmic expression) for BACH2. Confirmed mutation (CM) was identified in 8 cases and the CM index (number of confirmed mutations per 10 subclones) was distributed from 0 to 5. A CM index of 7 strongly positive (over-expression) cases with BACH2 were distributed from 0 to 5, and that of 7 negative and 6 positive cases were distributed from 0 to 1. Over-expression of BACH2 was statistically related to CM index (P = 0.008). In conclusion, over-expression of BACH2 is critical for ongoing SHM of IgHV in DLBCL, and our data suggest that BACH2 may play an essential role for SHM of the Ig gene in B-cell lymphoma.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/biossíntese , Cadeias Pesadas de Imunoglobulinas/genética , Região Variável de Imunoglobulina/genética , Linfoma Difuso de Grandes Células B/metabolismo , Hipermutação Somática de Imunoglobulina/genética , Sequência de Bases , Fatores de Transcrição de Zíper de Leucina Básica/genética , Humanos , Cadeias Pesadas de Imunoglobulinas/metabolismo , Região Variável de Imunoglobulina/metabolismo , Imuno-Histoquímica , Linfoma Difuso de Grandes Células B/genética , Dados de Sequência Molecular , Reação em Cadeia da Polimerase
11.
Pathol Int ; 61(12): 742-8, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22126382

RESUMO

Diffuse large B-cell lymphoma (DLBCL) rarely involves the duodenum, and its clinicopathological characteristics have not been well elucidated. We performed clinicopathological examinations and identified 15 patients with duodenal DLBCL using 18 gastric or colonic DLBCL as a control. Eleven of the 15 patients (73%) were subclassified by immunohistochemical analysis according to the Choi algorithm as germinal center B-cell-like (GCB) type, whereas the 18 control gastric and colonic DLBCL were predominantly subclassified as activated B-cell-like (ABC) type. The classifications according to organ involvement were statistically significant (P= 0.011 and P= 0.035). Macroscopically, the GCB lesions were varied, while all ABC lesions were ulcerative. Fluorescence in situ hybridization analysis revealed a higher frequency of t(14;18) translocation in patients with duodenal DLBCL (3 of 13) as compared with non-duodenal gastrointestinal tract DLBCL (0 of 18), however, the difference was not significant (P = 0.064). Furthermore, the three patients with t(14;18) translocations were classified as GCB. In addition, overall survival of patients was statistically different between those with and without t(14;18) translocation (P= 0.040). In conclusion, duodenal DLBCL predominantly exhibits GCB-type tumors and the frequency of t(14;18) translocation appears to be higher in duodenal GCB-type DLBCL compared to non-duodenal tumors.


Assuntos
Cromossomos Humanos Par 14/genética , Cromossomos Humanos Par 18/genética , Neoplasias Duodenais/genética , Centro Germinativo/patologia , Linfoma Difuso de Grandes Células B/genética , Translocação Genética/genética , Idoso , Idoso de 80 Anos ou mais , Neoplasias Duodenais/patologia , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade
12.
Mod Pathol ; 22(7): 940-9, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19396151

RESUMO

Although most follicular lymphomas are believed to be of nodal origin, they sometimes originate from the duodenum. We have reported that the latter differ from nodal follicular lymphomas in having lower clinical stages and uniformly low histological grades, along with variable region of immunoglobulin heavy chain gene (VH) usage that is more similar to mucosa-associated lymphoid tissue (MALT) lymphomas. Little is known, however, about whether they possess other characteristics of nodal follicular lymphomas, particularly ongoing mutations with follicular dendritic cells. We examined 17 cases for which PCR identified the monoclonal bands of the immunoglobulin gene. The duodenal cases showed ongoing mutations, but they lacked activation-induced cytidine deaminase (AID) expression, a statistically significant difference from the nodal cases (P<0.001), and their follicular dendritic cell networks were disrupted. Moreover, not only were VH deviations observed but also they used very restricted VH genes. Although the mechanisms of ongoing mutation without AID and follicular dendritic cell were not clarified, restricted VH usage strongly suggested that antigen stimulation was involved, and that was similar to MALT lymphomas. In conclusion, duodenal follicular lymphomas were shown to be unique, in that they had ongoing hypermutations such as nodal cases, but the mechanisms involved in the hypermutation were quite different; furthermore, restricted VH usage suggested a strong similarity to the antigen-dependent origin of MALT lymphomas.


Assuntos
Citidina Desaminase/metabolismo , Células Dendríticas Foliculares/patologia , Neoplasias Duodenais/patologia , Linfonodos/patologia , Linfoma Folicular/patologia , Hipermutação Somática de Imunoglobulina , Idoso , Biomarcadores Tumorais/metabolismo , DNA de Neoplasias/análise , Células Dendríticas Foliculares/enzimologia , Neoplasias Duodenais/enzimologia , Neoplasias Duodenais/genética , Feminino , Genes de Cadeia Pesada de Imunoglobulina , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Antígeno Ki-67/metabolismo , Linfonodos/embriologia , Linfoma Folicular/enzimologia , Linfoma Folicular/genética , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Translocação Genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA