RESUMO
Different studies have suggested that the expression of biomarkers related to lymphoid cell activation may provide information on the behavior of DLBCL. Most studies have concentrated on nodal or a mixture of nodal and extranodal lymphomas. The differential expression and potential clinical impact of these markers in a homogeneous group of extranodal DLBCLs are not well defined. In this study, we investigated the expression of three activation markers, Blimp1, Foxp1 and pStat3, in a cohort of 35 extranodal DLBCLs homogeneously treated with R-CHOP. Immunohistochemical stains were evaluated using an immunoreactivity score on representative paraffin sections. Blimp1 was positive in 55% (19/35), Foxp1 in 60% (21/35), and pStat3 in 69% (24/35) of our cases. We did not observe any statistical differences in the expression of these markers in GCB and non-GCB tumors or in gastrointestinal and non-gastrointestinal tumors. Blimp1 expression was negatively correlated with overall survival (OS) (p=0.001) in the whole series and in the non-GCB group (Muris algorithm) (p=0.002). Foxp1 positivity and pStat3 positivity had no impact on the outcome of the patients in the global cohort, but they were associated with a better survival in the non-GCB subgroup (p=0.033, p=0.044 respectively). Multivariate analysis showed that Blimp1 expression but not COO was an independent negative prognostic factor for OS (HR=17.5, 95%, CI=2.2-141.1, p=0.007). Our results suggest that these markers are differentially expressed and have different impacts on outcome in extranodal DLBCLs compared to nodal tumors, emphasizing the need to evaluate separately these and probably other markers in these subsets of tumors.
Assuntos
Fatores de Transcrição Forkhead/metabolismo , Regulação Neoplásica da Expressão Gênica , Linfoma de Células B/metabolismo , Fator 1 de Ligação ao Domínio I Regulador Positivo/metabolismo , Proteínas Repressoras/metabolismo , Fator de Transcrição STAT3/metabolismo , Adolescente , Adulto , Idoso , Algoritmos , Estudos de Coortes , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fosforilação , Resultado do Tratamento , Adulto JovemRESUMO
TACI is a membrane receptor of BAFF and APRIL, contributing to the differentiation and survival of normal B cells. Although malignant B cells are also subjected on TACI signaling, there is a remarkable intradisease and interindividual variability of TACI expression in B-cell malignancies. The aim of our study was to explore the possible role of TACI signaling in the biology of chronic lymphocytic leukemia (CLL), including its phenotypic and clinical characteristics and prognosis. Ninety-four patients and 19 healthy controls were studied. CLL patients exhibited variable TACI expression, with the majority of cases displaying low to undetectable TACI, along with low to undetectable BAFF and increased APRIL serum levels compared to healthy controls. CLL cells with high TACI expression displayed a better survival capacity in vitro, when cultured with BAFF and/or APRIL. Moreover, TACI expression was positively correlated with the presence of monoclonal gammopathy and inversely with CD11c expression. Therefore, our study provides further evidence for the contribution of BAFF/APRIL signaling to CLL biology, suggesting also that TACI detection might be useful in the selection of patients for novel targeting therapeutic approaches.
Assuntos
Fator Ativador de Células B/sangue , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/patologia , Proteína Transmembrana Ativadora e Interagente do CAML/sangue , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose/genética , Apoptose/imunologia , Linfócitos B/citologia , Linfócitos B/patologia , Antígeno CD11c/biossíntese , Diferenciação Celular/genética , Diferenciação Celular/imunologia , Feminino , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Paraproteinemias/genética , RNA Mensageiro/biossíntese , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Proteína Transmembrana Ativadora e Interagente do CAML/biossíntese , Proteína Transmembrana Ativadora e Interagente do CAML/genéticaAssuntos
Peritonite Tuberculosa/diagnóstico , Dor Abdominal/etiologia , Adulto , Antituberculosos/uso terapêutico , Líquido Ascítico , Biópsia , Diagnóstico Diferencial , Escavação Retouterina/patologia , Quimioterapia Combinada , Europa Oriental/etnologia , Feminino , Grécia , Ginecologia , Humanos , Laparoscopia , Peritônio/patologia , Peritonite Tuberculosa/tratamento farmacológico , Peritonite Tuberculosa/patologia , Peritonite Tuberculosa/fisiopatologia , Resultado do Tratamento , Adulto JovemRESUMO
Tyrosine-kinase inhibitors are very effective in patients with CML, but in most cases the disease relapses after their discontinuation. As a result, novel approaches should be considered, such as anti-survivin treatment or anti-survivin-based immunotherapy. To gain insight into the roles of survivin isoform expression and specific CD8(+) T cells in CML, we investigated 51 patients at different stages, both at diagnosis and during treatment. We demonstrated that (i) patients at advanced-stage displayed an increased expression of the standard-survivin form along with a significant decrease of survivin-2B and -ΔEx3 levels, (ii) patients in chronic phase with higher expression of the standard-survivin exhibited a 3.5-fold increased probability not to achieve an optimal response to imatinib (p=0.048), (iii) responders displayed a significant up-regulation of all survivin isoforms in bone marrow, and (iv) anti-survivin CD8(+) T cells were undetectable both at diagnosis and during treatment. Accordingly, our results question the validity of immunotherapeutic approaches targeting survivin in CML.
Assuntos
Progressão da Doença , Resistencia a Medicamentos Antineoplásicos/fisiologia , Proteínas Inibidoras de Apoptose/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Linfócitos T Citotóxicos/imunologia , Adulto , Idoso , Antineoplásicos/uso terapêutico , Benzamidas , Células Sanguíneas/metabolismo , Células da Medula Óssea/imunologia , Células da Medula Óssea/metabolismo , Epitopos de Linfócito T/imunologia , Feminino , Proteínas de Fusão bcr-abl/genética , Expressão Gênica/genética , Humanos , Mesilato de Imatinib , Proteínas Inibidoras de Apoptose/genética , Proteínas Inibidoras de Apoptose/imunologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/imunologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Leucócitos Mononucleares/imunologia , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/imunologia , Isoformas de Proteínas/genética , Isoformas de Proteínas/imunologia , Isoformas de Proteínas/metabolismo , Survivina , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND/AIMS/METHODS: To determine the frequency of Helicobacter pylori infection (Hp-I) in 73 patients with myelodysplastic syndromes (MDS) and 40 controls, serologic analyses of Hp and ¹³C-urease breath tests (INFAI) were performed. Gastric mucosal biopsy specimens were obtained to determine the presence of Hp-I using a rapid urease test, i.e. the Campylobacter-like organism (CLO) test, and cresyl violet staining. Peripheral blood (PB) flow cytometry for CD3, CD4, CD8, CD14, CD19 and CD34 was conducted in 35 patients and in controls. RESULTS: Hp-I was detected by: (a) serology in 75.34% of patients (p = 0.000), (b) INFAI in 57.69% of patients, (c) CLO in 60.71% of patients and (d) histological confirmation in 80.36% of patients (p = 0.001). No correlation between Hp-I and CD3, CD4, CD8, CD14, CD19 expression, leukemic transformation or death was observed. However, in 20 cases, significant variation in the PB lymphocytic proportion possibly attributable to Hp-I was ascertained, in contrast to the expected MDS ratio. CONCLUSION: Although there is no evidence for a causal relationship between Hp-I and MDS, the increased prevalence of Hp-I among the MDS patients is an interesting finding that deserves further investigation as it may indicate a common factor causing susceptibilities to both MDS and Hp-I or that Hp might influence the pathophysiology of MDS.
Assuntos
Infecções por Helicobacter/complicações , Helicobacter pylori , Síndromes Mielodisplásicas/complicações , Idoso , Antígenos CD/sangue , Estudos de Casos e Controles , Causalidade , Estudos de Coortes , Feminino , Grécia/epidemiologia , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/imunologia , Humanos , Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/imunologia , Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/sangue , Síndromes Mielodisplásicas/imunologiaRESUMO
BACKGROUND: The primary aim of this study was to evaluate a combined therapeutic intervention, including the dual endothelin receptor antagonist bosentan, in patients with carcinoid heart disease (CaHD). The efficacy of the treatment protocol was investigated using serological, echocardiographic, and clinical markers. PATIENTS AND METHODS: Since 2003, 40 patients with neuroendocrine tumours were identified; 14 had echocardiographic findings consistent with CaHD. Six of the 14 patients with CaHD and a New York Heart Association (NYHA) functional class >or= III received bosentan and were eligible for inclusion in this study. RESULTS: N-terminal pro-brain natriuretic peptide (NT-pro-BNP) had decreased 6 months after treatment with bosentan (median: 646 pg/ml vs. 400.5 pg/ml; p = 0.02); the right ventricular systolic pressure had decreased after 3 and 6 months (median: 69 mmHg vs. 61 mmHg, p = 0.02; median: 69 mmHg vs. 48.5 mmHg, p = 0.02); the 6-minute walk distance (6MWD) had significantly improved after 3 and 6 months of treatment (median: 293.5 vs. 406.5 m; p = 0.02; median: 293.5 vs. 578.5 m; p = 0.02). The NYHA functional class improved in 5/6 patients receiving bosentan. CONCLUSIONS: Combined treatment with bosentan is effective in patients with CaHD, based on functional class, 6MWD, and NT-pro-BNP. Further clarification of the CaHD fibrosis pathogenesis is needed to facilitate development of targeted antifibrotic therapeutic agents.
Assuntos
Anti-Hipertensivos/uso terapêutico , Doença Cardíaca Carcinoide/tratamento farmacológico , Antagonistas dos Receptores de Endotelina , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Sulfonamidas/uso terapêutico , Idoso , Anti-Hipertensivos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bosentana , Doença Cardíaca Carcinoide/sangue , Doença Cardíaca Carcinoide/diagnóstico , Terapia Combinada , Ecocardiografia Doppler , Teste de Esforço/efeitos dos fármacos , Feminino , Seguimentos , Neoplasias Gastrointestinais/patologia , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Neoplasias Ovarianas/patologia , Fragmentos de Peptídeos/sangue , Sulfonamidas/efeitos adversosRESUMO
BACKGROUND: B-type natriuretic peptide (BNP) and N-terminal-pro-BNP (NT-pro-BNP) are important diagnostic tools for patients with suspected cardiac disorders. The aim of this study was to evaluate the predictive value of plasma NT-pro-BNP in identifying cardiac metastases in patients with non-small cell lung cancer (NSCLC) and dyspnoea. PATIENTS AND METHODS: A total of 120 patients, median age 62 years (range 46-83), with NSCLC and dyspnoea were studied. Patients with heart failure or documented coronary artery disease were excluded. Echocardiographic imaging was used to detect cardiac metastases and estimate global left ventricular function. Ejection fraction and E/A ratio from transmitral inflow pattern were calculated. Plasma NT-pro-BNP was also measured. 72 patients (72/120, 60%) with cardiac metastases were identified. RESULTS: NT-pro-BNP was significantly higher in patients with metastases (1347.5 +/- 1004.30 pg/ml vs. 159.02 +/- 93.29 pg/ml; p = 0.001). No differences between groups, regarding s-creatinine (p = 0.45), haemoglobin (p = 0.71), left ventricular hypertrophy (p = 0.91), and diastolic dysfunction (p = 0.79), were observed. CONCLUSION: Plasma NT-pro-BNP is remarkably elevated in patients with NSCLC and myocardial/pericardial infiltrations and may be used as a sensitive marker for detecting cardiac metastases in these patients.
Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/secundário , Neoplasias Cardíacas/diagnóstico , Neoplasias Cardíacas/secundário , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/sangue , Feminino , Neoplasias Cardíacas/sangue , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/diagnóstico , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
RASSF1A, a key cell cycle related gene, is expressed in all hematopoietic cells, it is implicated in ras signaling pathway and its promoter hypermethylation is observed in a wide variety of solid tumors. Till now, RASSF1A methylation status has not been investigated in patients with chronic myeloid leukemia (CML). In this study, we analyzed 41 patients carrying the BCR-ABL rearrangement, in different stages of the disease. No patient displayed RASSF1A promoter methylation, although the K562 erythroleukemia cell line, bearing the BCR-ABL rearrangement, was found methylated. Thus, our findings indicate that RASSF1A methylation does not appear to represent a critical step in the pathogenesis and/or the progression of CML.
Assuntos
Metilação de DNA , DNA de Neoplasias/metabolismo , Regulação Leucêmica da Expressão Gênica , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Regiões Promotoras Genéticas , Proteínas Supressoras de Tumor/biossíntese , DNA de Neoplasias/genética , Feminino , Genes abl/genética , Células-Tronco Hematopoéticas/metabolismo , Humanos , Células K562 , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Masculino , Translocação Genética/genética , Proteínas Supressoras de Tumor/genéticaRESUMO
BACKGROUND: Cardiac tamponade (CT) as the primary clinical manifestation of lymphomas is extremely rare. Angioimmunoblastic T-cell lymphoma (AILT) is characterised by systemic disease usually presenting with generalised peripheral lymphadenopathy, hepatosplenomegaly, and bone marrow infiltration. CASE REPORT: We report on a 59-year-old male patient with CT as initial clinical manifestation of AILT. Coexistence with malignant pleural mesothelioma was additionally revealed. Cytologic examination of pericardial fluid presented diffuse lymphoid cells and sporadic malignant mesothelial cells. AILT diagnosis was confirmed by thoracoscopic mediastinal lymph node and bone marrow biopsy. Despite the presence of pleural effusion, the diagnosis of mesothelioma was initially established by cytologic ex-amination of pericardial fluid, due to the patient's critical cardiac condition requiring prompt subxiphoid pericardiocentesis. CONCLUSION: CT as primary clinical manifestation of AILT is very rare. This case reflects the differences in the underlying biology of AILT and consequently the vast spectrum of its clinical presentations. Coexistence of AILT with malignant pleural mesothelioma is also extremely rare.
Assuntos
Tamponamento Cardíaco/diagnóstico , Tamponamento Cardíaco/etiologia , Linfadenopatia Imunoblástica/complicações , Linfadenopatia Imunoblástica/diagnóstico , Linfoma/complicações , Linfoma/diagnóstico , Mesotelioma/complicações , Mesotelioma/diagnóstico , Humanos , Masculino , Pessoa de Meia-IdadeAssuntos
Infecções por Helicobacter/complicações , Leucemia Mieloide Aguda/prevenção & controle , Síndromes Mielodisplásicas/complicações , Infecções por Helicobacter/imunologia , Helicobacter pylori , Humanos , Leucemia Mieloide Aguda/etiologia , Leucemia Mieloide Aguda/imunologia , Modelos Biológicos , Síndromes Mielodisplásicas/imunologia , Fator de Necrose Tumoral alfa/sangueRESUMO
Recently, the acquired mutation JAK2-V617F has been described in the majority of patients with myeloproliferative disorders (MPDs). In this study we evaluated its clinical and laboratory correlates in 166 patients with MPDs. The mutation was detected by allele-specific PCR in 119 patients: 81.4% (35/43) of those with polycythemia vera, 69.1% (77/111) of those with essential thrombocythemia and 58.1% (7/12) of those with idiopathic myelofibrosis. The patients carrying the mutation were older (p=0.02) and displayed higher levels of Ht (p<0.01) and Hb (<0.01) and lower erythropoietin levels (p<0.01). Moreover, mutation-positive patients displayed a higher probability of having leucocytosis, splenomegaly and thrombotic events (three-fold, two-fold and two-fold, respectively) than mutation-negative patients. These correlations imply that the JAK2-V617F mutation may be useful for the classification and the management of patients with MPDs.
Assuntos
Janus Quinase 2/genética , Transtornos Mieloproliferativos/genética , Mutação Puntual/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Mieloproliferativos/diagnóstico , Transtornos Mieloproliferativos/enzimologia , Reação em Cadeia da PolimeraseRESUMO
Langerhans cell histiocytosis (LCH) of the female genital tract is very rare. A review of the literature revealed that only 12 cases of primary vulvar LCH have previously been published. We describe an additional case of LCH in which the disease was confined to the vulva. A 64-year-old woman was admitted to our hospital with a nodular mass on her left labium minus, and complete surgical excision was performed. On histological and immunohistochemical examination, the tumor fulfilled the criteria of LCH. A metastatic workup did not reveal any evidence of disease beyond the vulva. The patient received local radiotherapy, and 22 months later she is in excellent condition without local recurrence or metastatic disease.
Assuntos
Histiocitose de Células de Langerhans/patologia , Doenças da Vulva/patologia , Antígenos CD1/metabolismo , Biomarcadores Tumorais/metabolismo , Terapia Combinada , Feminino , Histiocitose de Células de Langerhans/metabolismo , Histiocitose de Células de Langerhans/terapia , Humanos , Pessoa de Meia-Idade , Radioterapia Adjuvante , Proteínas S100/metabolismo , Resultado do Tratamento , Doenças da Vulva/metabolismo , Doenças da Vulva/terapiaRESUMO
Non-Hodgkin's lymphoma (NHL) of the breast may be primary or secondary. Both are rare and there are no morphological criteria to make the differential diagnosis. Benign intramammary lymph nodes are often encountered, but the development of either primary or secondary lymphoma within an intramammary lymph node is extremely rare. We report the case of a 72-year-old woman who presented with a palpable mass in her right breast. A mammography showed a large intramammary lymph node from which a biopsy was taken. On morphological and immunohistochemical examination the tumor fulfilled the criteria of NHL originating in an intramammary lymph node. The patient received chemotherapy which led to the disappearance of the mass. A review of the literature revealed that this is the third reported case of primary NHL originating in an intramammary lymph node.