ABSTRACT
CD137 (also known as 4-1BB and TNFRSF9) is a member of the tumor necrosis factor receptor superfamily. Originally identified as a costimulatory molecule expressed by activated T cells and NK cells, CD137 is also expressed by follicular dendritic cells, monocytes, mast cells, granulocytes, and endothelial cells. Anti-CD137 immunotherapy has recently shown promise as a treatment for solid tumors and lymphoid malignancies in preclinical models. We defined the expression of CD137 protein in both normal and neoplastic hematolymphoid tissue. CD137 protein is expressed by follicular dendritic cells in the germinal center and scattered paracortical T cells, but not by normal germinal-center B cells, bone marrow progenitor cells, or maturing thymocytes. CD137 protein is expressed by a select group of hematolymphoid tumors, including classical Hodgkin lymphoma, T-cell and NK/T-cell lymphomas, and follicular dendritic cells neoplasms. CD137 is a novel diagnostic marker of these tumors and suggests a possible target for tumor-directed antibody therapy.
Subject(s)
Histiocytic Disorders, Malignant/diagnosis , Histiocytic Disorders, Malignant/metabolism , Hodgkin Disease/metabolism , Hodgkin Disease/therapy , Lymphoma, T-Cell/diagnosis , Lymphoma, T-Cell/metabolism , Tumor Necrosis Factor Receptor Superfamily, Member 9/metabolism , Biomarkers, Tumor/metabolism , Dendritic Cells, Follicular/metabolism , Dendritic Cells, Follicular/pathology , Flow Cytometry , Histiocytic Disorders, Malignant/pathology , Histiocytic Disorders, Malignant/therapy , Hodgkin Disease/diagnosis , Hodgkin Disease/pathology , Humans , Immunohistochemistry , Lymphocyte Subsets/metabolism , Lymphoid Tissue/metabolism , Lymphoid Tissue/pathology , Lymphoma, B-Cell/metabolism , Lymphoma, B-Cell/pathology , Lymphoma, T-Cell/pathology , Lymphoma, T-Cell/therapyABSTRACT
AIDS-related lymphomas (ARL) present high biological heterogeneity. For better characterization of this type of lymphoma, the objectives of the present study were to evaluate the expression of immunohistochemical markers of cell differentiation (CD10, Bcl-6, MUM-1) and determine cell origin profile according to Hans' classification of diffuse large B-cell lymphoma in AIDS patients. This study included 72 consecutive patients with ARL diagnosed at the University Hospital, Universidade Federal do Rio de Janeiro (UFRJ) and at the Brazilian Instituto Nacional de Câncer (INCA) from 2000 to 2006. The morphologic distribution of the lymphomas was the following: 61% were diffuse large B-cell lymphomas (DLBCLs), 15% were Burkitt's lymphomas, 13% were plasmablastic lymphomas, 10% were high-grade lymphomas and 1% was follicular lymphoma. The positivity for each immunohistochemical marker in DLBCLs, Burkitt's lymphoma and plasmablastic lymphoma was respectively: CD20, 84%, 100%, and 0; CD10, 55%, 100%, and 0; Bcl-6, 45%, 80%, and 0; MUM-1, 41%, 20%, and 88%. A higher positivity of CD20 (84% x 56%, p = 0.01) was found in DLBCL compared to non-DLBCL; in Burkitt's lymphomas a higher positivity of CD10 (100% x 49%, p = 0.04) and Bcl-6 (80% x 39%, p = 0.035) were found compared to non-Burkitt's lymphomas. Germinal center (GC) profile was detected in 60% of DLBCLs. Our study suggests particular findings in ARL, as the most frequent phenotype was GC, different from HIV-negative patients.
Subject(s)
Biomarkers, Tumor/metabolism , Interferon Regulatory Factors/metabolism , Lymphoma, AIDS-Related/metabolism , Neprilysin/metabolism , Proto-Oncogene Proteins c-bcl-6/metabolism , Adolescent , Adult , Aged , Cell Differentiation , Child , Female , Humans , Immunohistochemistry , Lymphoma, AIDS-Related/classification , Lymphoma, AIDS-Related/pathology , Male , Middle Aged , Phenotype , Young AdultABSTRACT
AIDS-related lymphomas (ARL) present high biological heterogeneity. For better characterization of this type of lymphoma, the objectives of the present study were to evaluate the expression of immunohistochemical markers of cell differentiation (CD10, Bcl-6, MUM-1) and determine cell origin profile according to Hans' classification of diffuse large B-cell lymphoma in AIDS patients. This study included 72 consecutive patients with ARL diagnosed at the University Hospital, Universidade Federal do Rio de Janeiro (UFRJ) and at the Brazilian Instituto Nacional de Câncer (INCA) from 2000 to 2006. The morphologic distribution of the lymphomas was the following: 61 percent were diffuse large B-cell lymphomas (DLBCLs), 15 percent were Burkitt's lymphomas, 13 percent were plasmablastic lymphomas, 10 percent were high-grade lymphomas and 1 percent was follicular lymphoma. The positivity for each immunohistochemical marker in DLBCLs, Burkitt's lymphoma and plasmablastic lymphoma was respectively: CD20, 84 percent, 100 percent, and 0; CD10, 55 percent, 100 percent, and 0; Bcl-6, 45 percent, 80 percent, and 0; MUM-1, 41 percent, 20 percent, and 88 percent. A higher positivity of CD20 (84 percent x 56 percent, p = 0.01) was found in DLBCL compared to non-DLBCL; in Burkitt's lymphomas a higher positivity of CD10 (100 percent x 49 percent, p = 0.04) and Bcl-6 (80 percent x 39 percent, p = 0.035) were found compared to non-Burkitt's lymphomas. Germinal center (GC) profile was detected in 60 percent of DLBCLs. Our study suggests particular findings in ARL, as the most frequent phenotype was GC, different from HIV-negative patients.
Subject(s)
Adolescent , Adult , Aged , Child , Female , Humans , Male , Middle Aged , Young Adult , Interferon Regulatory Factors/metabolism , Lymphoma, AIDS-Related/metabolism , Neprilysin/metabolism , /metabolism , Biomarkers, Tumor/metabolism , Cell Differentiation , Immunohistochemistry , Lymphoma, AIDS-Related/classification , Lymphoma, AIDS-Related/pathology , PhenotypeABSTRACT
The outcome of Hodgkin's lymphoma (HL) has markedly improved over the last few decades, placing HL among the human cancers with highest cure rates. However, data about treatment outcomes in developing countries are scarce. From 1996 to 2005, 370 consecutive patients with HL treated in three public institutions in Rio de Janeiro were identified. A total of 216 patients who presented with advanced stage (IIB-IV) HL were selected for the present analysis. Patients with advanced disease were treated with ABVD, complemented or not by radiation therapy. The median follow-up time of survivors was 6.3 years (1-11.8). Fifteen patients died during first-line treatment. The complete remission rate was 80 percent. The 5-year progression-free survival (PFS) and the 5-year overall survival (OS) probabilities were 69 percent and 83 percent, respectively. The 5-year PFS in low-risk and high-risk patients were 81 percent and 62 percent (p=0.003), respectively. The 5-year OS in low-risk and high-risk International Prognostic Score patients were 89 percent and 78 percent (p=0.02), respectively. The present study provides a representative estimate of current treatment results for advanced HL in public institutions in an urban area in Brazil. It is clear that full treatment can be given to most patients, although those with very low socio-economic status might require special attention and support. Since Brazil is a large country, with substantial interregional heterogeneity, a nationwide registry of HL patients is currently being implemented.
Os resultados do tratamento do linfoma de Hodgkin (LH) melhoraram substancialmente ao longo das últimas décadas e tornaram o LH uma das neoplasias humanas com maior chance de cura. Entretanto, os dados sobre tratamento em países em desenvolvimento são escassos. Entre 1996 e 2005, 370 pacientes consecutivos com LH tratados em três instituições públicas no Rio de Janeiro foram identificados. Destes, 216 em estádio avançado (IIB-IV) foram selecionados para esta análise. Os pacientes foram tratados com o protocolo ABVD (doxorrubicina, bleomicina, vinblastina e dacarbazina). A mediana do tempo de seguimento dos sobreviventes foi de 6,3 anos (1-11,8). Quinze pacientes morreram durante o tratamento de primeira linha. A probabilidade de sobrevida livre de progressão (SLP) em cinco anos e a probabilidade de sobrevida global (SG) em cinco anos foram de 69 por cento e 83 por cento, respectivamente. A SLP nos grupos de baixo risco e de alto risco, de acordo com o "International Prognostic Score", foi de 81 por cento e 62 por cento (p=0,003), respectivamente. A SG em cinco anos nos grupos de baixo risco e de alto risco foi de 89 por cento e 78 por cento (p=0,02), respectivamente. O presente estudo apresenta uma estimativa representativa dos resultados atuais do tratamento do LH avançado em instituições públicas no Brasil. Fica claro que o tratamento completo pode ser oferecido à grande maioria dos pacientes, embora aqueles com baixo status socioeconômico possam exigir atenção especial. Em vista das dimensões continentais do Brasil, com substancial heterogeneidade interregional, um registro nacional de pacientes com LH está sendo implementado.
Subject(s)
Humans , Male , Female , Adolescent , Young Adult , Middle Aged , Aged, 80 and over , Drug Therapy , Hodgkin Disease , LymphomaABSTRACT
The human germinal center-associated lymphoma (HGAL) gene has prognostic value in diffuse large B-cell lymphoma, and expression of its cognate protein is germinal center-specific. A previous study had suggested that HGAL protein expression might also be related to the outcome in patients with Hodgkin lymphoma (HL). The aim of this study was to confirm the prognostic impact of HGAL protein expression in an independent, well-characterized cohort of 232 patients with classic HL treated uniformly with doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD). Tissue microarray analysis showed HGAL staining in 188 specimens (81%). Failure-free survival (FFS) was superior in patients with early-stage disease, low-risk IPS, and HGAL-positive patients. The estimated 5-year FFS for HGAL-positive and HGAL-negative patients was 82% and 67%, respectively (p = 0.03). In the multivariate analysis, advanced stage and absence of HGAL staining were independent predictors of a worse FFS. This study confirms and validates recent findings of a correlation between HGAL expression and outcome in classical HL.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hodgkin Disease/drug therapy , Hodgkin Disease/metabolism , Neoplasm Proteins/biosynthesis , Adolescent , Adult , Aged , Aged, 80 and over , Bleomycin/administration & dosage , Brazil , Cohort Studies , Dacarbazine/administration & dosage , Doxorubicin/administration & dosage , Female , Germinal Center/metabolism , Germinal Center/pathology , Hodgkin Disease/pathology , Humans , Immunohistochemistry , Intracellular Signaling Peptides and Proteins , Male , Microfilament Proteins , Middle Aged , Predictive Value of Tests , Prognosis , Survival Analysis , Tissue Array Analysis , Treatment Outcome , Vinblastine/administration & dosage , Young AdultABSTRACT
Immunohistochemistry (IHC) has become an essential part of diagnosis and clinical research in lymphomas. There is considerable heterogeneity, however, in IHC findings regarding expression rate and positivity cut-offs, which creates a degree of uncertainty that has prevented its incorporation for prognostic purposes. The purpose of the present study was to assess intra- and interobserver agreement in scoring bcl-2 expression on IHC. The study materials were 81 diffuse large B-cell lymphomas. Slides were processed in the same laboratory, and were analyzed independently and in a blinded manner by four pathologists twice, at least 1 month apart. The positivity rates ranged from 31% to 41% in the first evaluation, and from 30% to 43% in the second evaluation. The two analyses by the same pathologist gave concordant results in 88-93% of cases (kappa = 0.71-0.83). Complete agreement among all observers varied from 72% to 79%. The experience of the observer did not influence intra-observer concordance. Cooperative analysis of discordant slides led to consensus in all cases. The variation observed in scoring bcl-2 expression is acceptable for use in lymphoma diagnosis and classification. The use of IHC stratification, however, for clinical decisions regarding treatment will require standardization and centralized consensus review, and must await the results of ongoing prospective trials.
Subject(s)
Lymphoma, Large B-Cell, Diffuse/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Consensus , Humans , Immunohistochemistry , Lymph Nodes/pathology , Lymphoma, Large B-Cell, Diffuse/pathology , Observer Variation , Reproducibility of ResultsABSTRACT
O desenvolvimento do centro germinativo pelo linfoma de Burkitt cria dificuldades diagnósticas de grande conseqüência clínica. Descrevemos o caso de uma criança do sexo masculino com nove meses de idade, com massa tumoral osteilítica localizada na mandíbula. Ao exame físico, gânglio cervical aumentado, próximo à massa. Gânglios paravertebrais aumentados foram observados através de tomografia computadorizada. A biopsia do gânglio paravertebrais aumentados foram observados através de tomografia computadorizada. A biópsia do gânglio cervical mostrou centros germinativos hiperplásicos ao lado de outros parcial ou totalmente substituídos pelo linfoma. O aspecto de "céu estrelado" simulava, ao pequeno aumento, uma hiperplasia linfóide reacional. O estudo dos diversos padröes de centro germinativo foi essencial para o diagnóstico. Exame imuno-histoquímico mostrou células neoplásicas CD20+; a hibridizaçäo in situ para a presença de EBV foi negativa
