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1.
Cancer Sci ; 111(1): 219-228, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31729088

RESUMO

Use of immune index is a new potential approach for cancer classification and prediction. To investigate the status and clinical effect of immune index in gallbladder cancer (GBC), 238 GBC patients from Zhongshan Hospital affiliated to Fudan University were involved in the present study, including 113 patients in a training set and 125 patients in a validation set. Five immune cells (macrophages, neutrophils, regulatory T cells, cytotoxic T cells and mast cells) were selected based on a literature review and the immune index for each patient was calculated using the LASSO regression. A low immune index (<1) was defined as immunotype A and a high immune index (≥1) was defined as immunotype B. The 5-year overall survival rate for immunotype A was higher than that for immunotype B in the training set and the validation set (70.0% vs 37.0%, P < 0.001; 68.9% vs 47.5%, P = 0.002; respectively). Moreover, the immune index showed higher prediction efficiency compared with all the single immune cells which we selected. When combined with the immune index, the areas under the curve (AUC) of the TNM staging system in both sets were elevated from 0.677 to 0.787 and from 0.631 to 0.694, respectively. Interestingly, gemcitabine-based chemotherapy only benefits stage II patients of immunotype B and stage III patients of both immunotype A and immunotype B (P = 0.015, P = 0.030, P = 0.011, respectively) but does not work in stage II patients of immunotype A (P = .307). Taken together, the immune index could effectively predict prognosis and the benefits of gemcitabine-based chemotherapy and might improve on the TNM staging system.


Assuntos
Neoplasias da Vesícula Biliar/imunologia , Neoplasias da Vesícula Biliar/patologia , Imunidade/imunologia , Área Sob a Curva , Quimioterapia Adjuvante/métodos , Feminino , Humanos , Imunofenotipagem/métodos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Prognóstico , Taxa de Sobrevida
2.
Virchows Arch ; 475(6): 771-779, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31686194

RESUMO

The aim of this study was to review the histopathological, phenotypic, and molecular characteristics of pediatric-type follicular lymphoma (PTFL) and to assess the diagnostic value of novel immunohistochemical markers in distinguishing PTFL from follicular hyperplasia (FH). A total of 13 nodal PTFLs were investigated using immunohistochemistry, fluorescence in situ hybridization (FISH), and PCR and were compared with a further 20 reactive lymph nodes showing FH. Morphologically, PTFL cases exhibited a follicular growth pattern with irregular lymphoid follicles in which the germinal centers were composed of numerous blastoid cells showing a starry-sky appearance. Immunohistochemistry highlighted preserved CD10 (13/13) and BCL6 (13/13) staining, CD20 (13/13) positivity, a K light chain predominance (7/13), and partial BCL2 expression in 6/13 cases (using antibodies 124, E17, and SP66). The germinal center (GC)-associated markers stathmin and LLT-1 were positive in most of the cases (12/13 and 12/13, respectively). Interestingly, FOXP-1 was uniformly positive in PTFL (12/13 cases) in contrast to reactive GCs in FH, where only a few isolated positive cells were observed. FISH revealed no evidence of BCL2, BCL6, or MYC rearrangements in the examined cases. By PCR, clonal immunoglobulin gene rearrangements were detected in 100% of the tested PTFL cases. Our study confirmed the unique morphological and immunophenotypic features of PTFL and suggests that FOXP-1 can represent a novel useful diagnostic marker in the differential diagnosis between PTFL and FH.


Assuntos
Fatores de Transcrição Forkhead/metabolismo , Linfoma de Células B/patologia , Linfoma Folicular/metabolismo , Linfoma Folicular/patologia , Proteínas Repressoras/metabolismo , Adolescente , Adulto , Criança , Diagnóstico Diferencial , Humanos , Imuno-Histoquímica/métodos , Imunofenotipagem/métodos , Linfoma de Células B/diagnóstico , Linfoma de Células B/metabolismo , Linfoma Folicular/diagnóstico , Masculino , Estatmina/metabolismo , Adulto Jovem
3.
Presse Med ; 48(7-8 Pt 1): 807-815, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31447332

RESUMO

Chronic lymphocytic leukemia is the most frequent adult leukemia. Eighty per cent of the patients are asymptomatic at diagnosis and 30% of the patients will be never treated. The diagnosis is based on the blood smear examination and immunophenotyping by flow cytometry of blood lymphocytes. The first line option is immunochemotherapy in 90% of the patients without genetic abnormalities associated with chemo resistance. The use of new compounds targeting different pathways is more frequent especially in relapsing patients and could be an alternative to the chemotherapy in the future. Asymptomatic patients with a stable disease assessed by the specialist can be followed by the general practitioner with a blood count and clinical examination every six months or once a year.


Assuntos
Leucemia Linfocítica Crônica de Células B , Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Diagnóstico Diferencial , Humanos , Imunofenotipagem/métodos , Imunoterapia , Leucemia Linfocítica Crônica de Células B/classificação , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/patologia , Leucemia Linfocítica Crônica de Células B/terapia , Terapia de Alvo Molecular/métodos , Terapia de Alvo Molecular/tendências , Prognóstico , Inibidores de Proteínas Quinases/uso terapêutico , Terapias em Estudo/métodos , Terapias em Estudo/tendências
4.
Presse Med ; 48(7-8 Pt 1): 850-858, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31447334

RESUMO

Follicular lymphoma, the second most common lymphoma, is characterized by its slow growth and is often considered incurable in advanced stages. Progresses in biology have contributed to better understand the complex and successive mechanisms of development of this pathology, whose diagnosis is based on a lymph node biopsy. However, the prognosis of the patients is heterogeneous and several indexes have been proposed to identify groups of patients with a similar life expectancy, in order to guide the therapeutic choices. The treatment has been modified in the last 20 years by the emergence of anti-CD20 monoclonal antibodies which constitute, alone or in combination, of the cornerstone of therapeutic management. After staging using, in particular, 18-fluorodeoxyglucose positron emission tomography, the therapeutic strategy will be adapted for each patient, ranging from simple watchful waiting to a combination of chemotherapy and anti-CD20 antibodies. Relapses (which often require a new lymph node biopsy to eliminate a possible histological transformation into an aggressive lymphoma with poorer prognosis) remain common but are still accessible to effective therapeutic interventions. Thanks to these advances, the median life expectancy of patients with follicular lymphoma now exceeds 15 years.


Assuntos
Linfoma Folicular , Biópsia , Diagnóstico Diferencial , Humanos , Imunofenotipagem/métodos , Imunoterapia/métodos , Imunoterapia/tendências , Expectativa de Vida , Linfoma Folicular/diagnóstico , Linfoma Folicular/epidemiologia , Linfoma Folicular/patologia , Linfoma Folicular/terapia , Técnicas de Diagnóstico Molecular , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/terapia , Medicina de Precisão/métodos , Medicina de Precisão/tendências , Prognóstico , Taxa de Sobrevida , Terapias em Estudo/métodos , Terapias em Estudo/tendências
5.
Presse Med ; 48(7-8 Pt 1): 816-824, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31439443

RESUMO

Diagnosis of mature B cell malignancies is highly multidisciplinary. Biological tools provide diagnostic, prognostic and theranostic information. Biological hematology allows considering mature B cell diseases from two perspectives : cellular and molecular approaches. Cytomorphology and flow cytometry are tools from cell hematology. Conventional cytogenetics, FISH and molecular biology are tools from molecular hematology. NGS is a new technique that could dramatically change diagnostic and therapeutic management of B cell malignancies in the near future. Integration of clinical, pathological and biological data allows for personalized management of these diseases.


Assuntos
Técnicas de Laboratório Clínico/métodos , Leucemia de Células B/diagnóstico , Linfoma de Células B/diagnóstico , Integração de Sistemas , Hibridização Genômica Comparativa/métodos , Citodiagnóstico/métodos , Análise Citogenética/métodos , Análise Mutacional de DNA/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Imunofenotipagem/métodos , Hibridização in Situ Fluorescente/métodos , Leucemia de Células B/genética , Leucemia de Células B/patologia , Linfoma de Células B/genética , Linfoma de Células B/patologia , Técnicas de Diagnóstico Molecular/métodos , Imagem Multimodal/métodos , Imagem Multimodal/tendências
6.
J Cancer Res Clin Oncol ; 145(11): 2803-2811, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31463716

RESUMO

BACKGROUND: Flow cytometry (FCM) plays a crucial role in the differential diagnosis of Burkitt lymphoma/leukemia (BL) and B-cell precursor acute lymphoblastic leukemia (BCP-ALL). The presence of surface IgM (sIgM) alone or with light chain restriction indicates a mature blast phenotype (BIV by EGIL) and is usually observed in BL. However, sIgM expression could also be detected in transitional BCP-ALL cases. These similarities in immunophenotype and ambiguous correspondence with other laboratory findings may challenge the correct BL diagnostics. METHODS: We retrospectively reviewed the available data from immunophenotypic, morphological, cytogenetic, and molecular genetic studies of 146 children (85 boys and 61 girls) with a median age of 10 years (range 0-18 years) who were diagnosed with BL and BCP-ALL. The blasts' immunophenotype was studied by multicolor FCM. The conventional cytogenetic analysis included G-banded karyotyping and fluorescence in situ hybridization (FISH). RESULTS: In 54 children classified as BIV-ALL according to the EGIL, it was demonstrated that sIgM in a minority of cases can be associated with various types of BCP-ALL. Analysis of the antigen expression profile of 105 patients with verified BL (n = 21) and BCP-ALL (n = 84) showed significant differences in BL and the sIgM(+) vs BCP-ALL immunophenotype. Thus, even in cases of ambiguous sIgM expression, these two diseases could be reliably discriminated by complex immunophenotyping. Moreover, 10 patients (7 boys and 3 girls) with BL leukemic cells did not express sIgM, and they were diagnosed with BL on the basis of other laboratory and clinical signs. CONCLUSIONS: In conclusion, our study shows that BIV subtype is heterogeneous group of leukemia including not only the BL, but also BCP-ALL. In ambiguous cases, only a combination of multiple immunophenotypic, cytomorphologic, and genetic diagnostic technologies can allow the precise discrimination of BL and BCP-ALL and selection of the appropriate treatment scheme.


Assuntos
Linfócitos B/patologia , Citometria de Fluxo/métodos , Imunofenotipagem/métodos , Cariotipagem/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras B/classificação , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Prognóstico , Estudos Retrospectivos
7.
Virchows Arch ; 475(4): 513-518, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31388760

RESUMO

An accurate diagnosis of clinically distinct subgroups of aggressive mature B cell lymphomas is crucial for the choice of proper treatment. Presently, precise recognition of these disorders relies on the combination of morphological, immunophenotypical, and cytogenetic/molecular features. The diagnostic workup in such situations implies the application of costly and time-consuming analyses, which are not always required, since an intensified treatment option is reasonably reserved to fit patients. The Italian Group of Haematopathology proposes herein a practical algorithm for the diagnosis of aggressive mature B cell lymphomas based on a stepwise approach, aimed to select cases deserving molecular analysis, in order to optimize time and resources still assuring the optimal management for any patient.


Assuntos
Algoritmos , Linfoma de Células B/diagnóstico , Humanos , Imunofenotipagem/métodos , Hibridização in Situ Fluorescente/métodos
8.
Surg Pathol Clin ; 12(3): 671-686, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31352980

RESUMO

Increasing evidence supports the prognostic significance of measurable residual disease (MRD) in acute myeloid leukemia (AML). Dynamic MRD assessment for patients with AML complements baseline patient risk assessment factors in determining patient prognosis. MRD status may also be helpful in informing therapeutic decisions. The European Leukemia Net MRD working party recently issued consensus recommendations for the use of MRD in AML. The Food and Drug Administration also issued advice for using MRD in trials of hematologic malignancies. This article discusses MRD testing, highlights the challenges in adopting MRD testing in clinical practice, and provides insights into the future of the field.


Assuntos
Leucemia Mieloide Aguda/diagnóstico , Neoplasia Residual/diagnóstico , Biomarcadores Tumorais/metabolismo , Citometria de Fluxo/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Imunofenotipagem/métodos , Leucemia Mieloide Aguda/terapia , Terapia de Alvo Molecular/métodos , Neoplasia Residual/terapia , Fenótipo , Reação em Cadeia da Polimerase em Tempo Real/métodos , Indução de Remissão/métodos , Sensibilidade e Especificidade , Manejo de Espécimes/métodos
9.
Surg Pathol Clin ; 12(3): 709-718, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31352983

RESUMO

The diagnosis of B-cell lymphoma unclassifiable with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma, also called gray zone lymphoma (GZL), is frequently challenging. Incorrect diagnosis as either classic Hodgkin lymphoma or diffuse large B-cell lymphoma has significant implications for choice of upfront therapy based on recent large multi-institutional series from the United States and Europe. These studies have clarified some diagnostic challenges and provided guidance on the spectrum of morphologic features in this entity. This article clarifies some of the diagnostic conundrum surrounding GZL and provides an evidence-based approach to GZL diagnosis using morphology and immunohistochemistry.


Assuntos
Linfoma de Células B/patologia , Idoso , Biomarcadores Tumorais/metabolismo , Diagnóstico Diferencial , Infecções por Vírus Epstein-Barr/patologia , Feminino , Doença de Hodgkin/patologia , Humanos , Imunofenotipagem/métodos , Antígeno Ki-1/metabolismo , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias do Timo/patologia
10.
Surg Pathol Clin ; 12(3): 719-731, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31352984

RESUMO

Technical advances in diagnostic modalities have led to the characterization of indolent lymphoid disorders similar to the in situ lesions described in epithelial malignancies. These early and indolent lymphoid lesions share clinicopathologic characteristics with well-characterized lymphoid malignancies such as chronic lymphocytic leukemia and follicular lymphoma. The in situ lesions have an indolent clinical course with only a minor subset shown to progress to frank malignancies. In addition to the in situ lesions, new indolent lymphoproliferative disorders have been recently characterized. Diagnosis and characterization of these indolent lesions is necessary to prevent overtreatment with aggressive therapeutic regimens.


Assuntos
Linfoma Folicular/patologia , Transtornos Linfoproliferativos/patologia , Linfócitos B/patologia , Diagnóstico Diferencial , Humanos , Imunofenotipagem/métodos , Leucemia Linfocítica Crônica de Células B/patologia , Linfocitose/patologia , Linfoma de Célula do Manto/patologia , Prognóstico
11.
J Med Case Rep ; 13(1): 223, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31327318

RESUMO

INTRODUCTION: Post-transplant lymphoproliferative disorder is a serious disorder which occurs post hematopoietic stem cell transplant or solid organ transplantation. T-prolymphocytic leukemia is a T cell type monomorphic post-transplant lymphoproliferative disorder which accounts for only 2% of all mature lymphocytic leukemias in adults over the age of 30. CASE PRESENTATION: A 59-year-old man of Chinese ethnicity presented to our hematology unit with headache, lethargy, and exertional dyspnea for the past 1 month. He underwent an uneventful cadaveric renal transplant 20 years ago for chronic glomerulonephritis-induced end-stage renal disease. He had been on long-term immunosuppressants since then consisting of orally administered prednisolone 10 mg daily and orally administered cyclosporine A 50 mg twice daily. On examination, he was pale with a palpable liver and spleen. He had a functioning renal graft. Marrow flow cytometry confirmed T-prolymphocytic leukemia with lymphocytes expressing CD2, CD3, CD7, CD52, and TCL-1. His human T-cell lymphotropic virus and Epstein-Barr virus serology and deoxyribonucleic acid (DNA) were negative. He was treated with one cycle of cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy to which he failed to respond. In view of his renal allograft, he was not suitable for alemtuzumab due to the risk of nephrotoxicity. He was given orally administered venetoclax but he died on day 17 due to severe auto tumor lysis syndrome. CONCLUSION: The place of immunophenotyping in the diagnosis and treatment of this disorder is of significant importance. More research needs to be carried out to further comprehend the pathophysiology and treatment modalities for this disorder.


Assuntos
Transplante de Rim/efeitos adversos , Transtornos Linfoproliferativos/diagnóstico , Erros de Diagnóstico , Evolução Fatal , Humanos , Imunofenotipagem/métodos , Leucemia Prolinfocítica/diagnóstico , Transtornos Linfoproliferativos/imunologia , Masculino , Pessoa de Meia-Idade
12.
Vet Immunol Immunopathol ; 213: 109889, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31307671

RESUMO

Blocking immunoglobulin G (IgG) binding receptors on leukocytes is an established and highly recommended preventive procedure for immunological assays. Failing to prevent such nonspecific binding can lead to erroneous results. Several studies testing different blocking reagents have been performed in murine or human cells, however, there are no specific studies on bovine cells. Our study aimed to investigate the efficiency of blocking reagents to inhibit the nonspecific binding of mouse monoclonal antibodies (mAbs) to bovine peripheral blood cells. We observed nonspecific interactions of IgG2a and IgG2b negative isotypes with bovine leukocytes, but not IgG1. We found that these nonspecific bindings could be eliminated by blocking with purified mouse IgG, whereas little or no blocking effect was observed when bovine serum or Mouse Seroblock FcR were applied. Moreover, in the absence of an efficient blocking reagent, the percentage of CD335 positive cells was significantly higher than in the group previously blocked with mouse IgG. Based on these results, and due to the lack of specific commercial blocking reagents for bovine cells, our recommendation is to use purified mouse IgG as a blocking reagent for immune assays targeting bovine leukocytes in order to enhance the accuracy of the results.


Assuntos
Anticorpos Monoclonais/imunologia , Imunofenotipagem/métodos , Leucócitos Mononucleares/imunologia , Receptores Fc/imunologia , Erro Experimental , Animais , Bovinos , Epitopos/imunologia , Citometria de Fluxo , Imunoglobulina G/imunologia , Imunoglobulina G/isolamento & purificação , Imunofenotipagem/normas , Camundongos , Ligação Proteica
13.
Asian Pac J Cancer Prev ; 20(7): 2109-2115, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31350973

RESUMO

Background: Gas station workers are exposed to carcinogenic substances with impact on the hematologic and immune systems. The aim was to apply the immunophenotyping as a tool in the biological monitoring. Methods: This is a workplace-based case-control study with 49 workers and 26 controls. Medical interviews, hematological exams, and immunophenotyping analyses were performed. According to risk behavior (cleaning flannel and mistrust in the automatic fuel supply) the workers were divided into two groups: low risk (group 1) and high risk (group 2). Results: The results showed that CD16, HLA-DR, CD25, CD56+, CD16 CD56 low, and CD56 high expressions were higher in workers when compared to the control group (P =0.020, P =0.001, P =0.001; P =0.034, P=0.023, and P =0.008, respectively). The expressions of CD2, CD8, CD10, CD8low, and CD4/CD8 ratios were lower (P =0.016, P =0.001, P=0.001, P= 0.017, P = 0.0259, and P =0.029, respectively). Headache and paresthesia complaints were associated with workers when compared to the control group (OR = 4.091, 95% CI, 1.400 -11.951, P = 0.014; OR =12.12, 95% CI, 1.505 - 97.61, P =0.004). Using cleaning flannel and mistrust in the automatic fuel supply (risk behaviors) were associated with group 2 (OR = 9.71, 95% CI, 2.60-36.26, P = 0.005; OR = 18.18, 95% CI, 2.04-161.37, P = 0.004). Conclusions: The results strengthen the worker's immunosuppression hypothesis, which may contribute to some disorders and the carcinogenesis process. The evaluation of the immune system by flow cytometry is a promising tool for monitoring blood malignancy risk in addition to regular classic hematological exams.


Assuntos
Biomarcadores Tumorais/análise , Gasolina/efeitos adversos , Neoplasias Hematológicas/diagnóstico , Imunidade Celular/imunologia , Imunofenotipagem/métodos , Doenças Profissionais/diagnóstico , Exposição Ocupacional/efeitos adversos , Adulto , Poluentes Ocupacionais do Ar/efeitos adversos , Antígenos CD/metabolismo , Estudos de Casos e Controles , Feminino , Seguimentos , Antígenos HLA/metabolismo , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/etiologia , Humanos , Imunidade Celular/efeitos dos fármacos , Masculino , Doenças Profissionais/sangue , Doenças Profissionais/etiologia , Prognóstico , Subpopulações de Linfócitos T/imunologia
14.
BMC Med ; 17(1): 106, 2019 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-31164128

RESUMO

BACKGROUND: Intratumoral immune infiltrates have manifested a robust prognostic signature in patients with hepatocellular carcinoma (HCC). We hypothesized that a novel tissue-related immune signature (TRIS) could improve the prediction of postoperative survival for patients diagnosed with early/intermediate HCC. METHODS: Twenty-eight immune features were immunohistochemically examined on 352 HCC specimens. The LASSO Cox regression model was used to construct a five-feature-based TRIS. The univariate and multivariate Cox analyses were performed. Based on independent predictors, the immune-clinical prognostic index (ICPI) was established. Performance assessment was measured with C-index and compared with seven traditional staging systems. The independent validation cohort (n = 393) was included to validate the model. RESULTS: By using the LASSO method, the TRIS were constructed on the basis of five immune features, CD3intratumoral (T), CD27T, CD68peritumoral (P), CD103T, and PD1T. Multivariate Cox analysis showed that the TRIS was an independent prognostic predictor. In the training cohort, γ-glutamyl transferase, tumor diameter, tumor differentiation, and TRIS were incorporated into the ICPI. The ICPI presented satisfactory discrimination ability, with C-index values of 0.691 and 0.686 in the training and validation cohorts, respectively. Compared with seven conventional staging systems (C-index, training cohort, 0.548-0.597; validation cohort, 0.519-0.610), the ICPI exhibited better performance for early/intermediate-stage HCCs. Further, the patients were categorized into three subgroups with X-tile software, and the stratified ICPI presented a superior corrected Akaike information criterion and homogeneity in both cohorts. CONCLUSIONS: Our ICPI was a useful and reliable prognostic tool which may offer good individualized prediction capability for HCC patients with early/intermediate stage.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Imunofenotipagem , Neoplasias Hepáticas/diagnóstico , Linfócitos do Interstício Tumoral/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Estudos de Coortes , Feminino , Humanos , Imuno-Histoquímica , Imunofenotipagem/métodos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Linfócitos/patologia , Linfócitos do Interstício Tumoral/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Análise de Sobrevida , Análise Serial de Tecidos , Transcriptoma
15.
J Exp Clin Cancer Res ; 38(1): 190, 2019 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-31072360

RESUMO

BACKGROUND: One of the most potent costimulatory molecules involved in the recognition and killing of tumor cells is CD80. However, its role and the molecular mechanisms regulating its expression in sporadic colorectal carcinogenesis remain elusive. Here, we provide evidence for CD80 overexpression in human colon epithelial cells derived from preneoplastic mucosa. METHODS: Expression of CD80 on colonic epithelial cells isolated from normal human colonic mucosa, preneoplastic and neoplastic specimens was assessed by flow cytometry. WT and CD80KO mice received azoxymethane to induce colon preneoplastic lesions and sacrificed to perform histology, flow cytometry analysis and immunohistochemistry of colonic mucosa. Some WT mice were treated with a monoclonal anti-CD80 antibody following AOM administration. Primary colon epithelial cells and CT26 cell line were used to quantify the expression of CD80 in response to pro-oxidant stimuli. Specific pharmacological inhibitors and siRNA silencing were used to inhibit MAPK pathways and STAT3. RESULTS: CD80 expression was significantly increased in colon epithelial cells of human preneoplastic lesions. In the AOM model, CD80 impairment by administration of neutralizing antibodies or use of CD80 knockout mice enhanced dysplasia development. In vitro, CD80 upregulation was induced by oxidative stress in colon cancer cells and primary colon epithelial cells. In addition, reactive oxygen species could induce CD80 expression via the JNK and p38 MAPK pathways, that activated STAT3 transcription factor in colon cancer epithelial cells. CONCLUSION: This study provide evidence for a major role of CD80 in orchestrating immune surveillance of colon preneoplastic lesions and might help to develop novel approaches that exploit anti-tumor immunity to prevent and control colon cancer.


Assuntos
Antígeno B7-1/genética , Neoplasias do Colo/genética , Lesões Pré-Cancerosas/genética , Fator de Transcrição STAT3/genética , Animais , Antígeno B7-1/imunologia , Carcinogênese/genética , Carcinogênese/imunologia , Colo/metabolismo , Colo/patologia , Neoplasias do Colo/imunologia , Neoplasias do Colo/patologia , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Citometria de Fluxo , Regulação Neoplásica da Expressão Gênica , Humanos , Imunofenotipagem/métodos , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Camundongos , Camundongos Knockout , Estresse Oxidativo/genética , Lesões Pré-Cancerosas/imunologia , Lesões Pré-Cancerosas/patologia , Cultura Primária de Células , Transdução de Sinais/genética , Proteínas Quinases p38 Ativadas por Mitógeno/genética
16.
Pediatr Dermatol ; 36(4): 477-481, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31120154

RESUMO

BACKGROUND: Pediatric mastocytosis differs from adult mastocytosis in its presentation and clinical course. However, the data regarding the immunophenotypic characterization of mast cells in children are limited. Our objective was to evaluate the immunophenotype of mast cells in pediatric mastocytosis and correlate it with the clinical course. METHODS: Biopsy specimens of children with cutaneous mastocytosis were retrieved from the institutions of pathology and were stained for CD25, CD2, and CD30. The percentage of mast cells and the staining intensity were correlated with the clinical data. RESULTS: Twenty-five biopsy specimens were included in the study. Patients' average age was 15.4 at presentation and 37.5 months at biopsy performance. Clinical presentations included maculopapular cutaneous mastocytosis in 79% and mastocytoma in 21% of cases. CD25, CD2, and CD30 were positive in 60%, 44%, and 84% of the biopsy specimens, respectively. The staining score was significantly higher for CD30 as compared to those for CD25 and CD2 (P = 0.02). No correlation was found between the immunophenotype and the clinical form or course of disease. CONCLUSIONS: Our results confirm that CD30 is a sensitive marker for pediatric-onset mastocytosis. Nevertheless, its expression does not correlate with clinical subtype or clinical course. The sensitivity of CD25 is higher than that of CD2 in skin lesions.


Assuntos
Imunofenotipagem/métodos , Antígeno Ki-1/imunologia , Mastócitos/imunologia , Mastocitose Cutânea/patologia , Mastocitose Cutânea/fisiopatologia , Neoplasias de Tecido Conjuntivo/patologia , Adolescente , Fatores Etários , Biomarcadores/análise , Biópsia por Agulha , Antígenos CD2/imunologia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Imuno-Histoquímica , Lactente , Subunidade alfa de Receptor de Interleucina-2/imunologia , Israel , Masculino , Mastócitos/patologia , Mastocitoma/imunologia , Mastocitoma/patologia , Mastocitose Cutânea/imunologia , Neoplasias de Tecido Conjuntivo/imunologia , Neoplasias de Tecido Conjuntivo/fisiopatologia , Prognóstico , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Estatísticas não Paramétricas
17.
PLoS One ; 14(5): e0217163, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31116766

RESUMO

Understanding the immunological phenotype of transplant recipients is important to improve outcomes and develop new therapies. Immunophenotyping of whole peripheral blood (WPB) by flow cytometry is a rapid method to obtain large amounts of data relating to the outcomes of different transplant treatments with limited patient impact. Healthy individuals and patients with type 1 diabetes (T1D) enrolled in islet transplantation were recruited and WPB was collected. 46 fluorochrome-conjugated mouse-anti-human antibodies were used (43 of 46 antibodies were titrated). BD cytometer setup and tracking beads were used to characterize and adjust for cytometer performance. Antibody cocktails were pre-mixed <60 minutes before staining. Multicolour panels were designed based on fluorochrome brightness, antigen density, co-expression, and fluorochrome spillover into non-primary detectors in each panel on a 5 laser flow cytometer. WPB sample staining used 50-300 µl WPB for each panel and was performed within 2 hours of blood sample collection. Samples were acquired on a BD-LSRFortessa. The operating procedures, including specimen collection, antibody cocktails, staining protocol, flow-cytometer setup and data analysis, were standardized. The staining index of 43 antibodies and the spillover spreading matrix for each panel was calculated. The final concentrations for the 46 antibodies used was determined for staining of WPB samples. Absolute cell-count and 7 leukocyte profiling panels consisting of subsets and/or status of granulocytes, monocytes, dendritic, B, NK, and T cells including regulatory T cells (Tregs) and NKT were designed and established on a 5 laser BD-LSR Fortessa. 13 T1D patients, including 4 islet transplant recipients and 8 healthy controls, were evaluated. The ability to reproducibly measure immune subsets and immune-profiles of islet transplant patients up to 18 months post transplantation has been established as a tool to measure immune cell reconstitution after transplantation.


Assuntos
Anticorpos/imunologia , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/terapia , Citometria de Fluxo/normas , Imunofenotipagem/métodos , Transplante das Ilhotas Pancreáticas/métodos , Transplantados/estatística & dados numéricos , Anticorpos/sangue , Estudos de Casos e Controles , Ensaios Clínicos como Assunto , Diabetes Mellitus Tipo 1/sangue , Humanos
18.
J Clin Pathol ; 72(9): 597-602, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31088938

RESUMO

AIMS: Mammary angiomatosis is a rare, benign vascular lesion that morphologically mimics low-grade angiosarcoma (LGAS). To date, only occasional reports of this entity have been published, none of which included analysis by immunohistochemistry. The purpose of this study was to further characterise mammary angiomatosis by clinical, histological, and immunohistochemical means while emphasising distinguishing features from LGAS. METHODS: Seven cases of primary mammary angiomatosis were evaluated. For one patient, a subsequent recurrence was also evaluated. RESULTS: All patients were female with a median age at presentation of 51 years (range: 19-58 years). The most common clinical presentation was that of a palpable abnormality or mass (5/8) and the median primary tumour size was 3.1 cm (range: 2-9 cm). Of the six patients with follow-up, one developed a recurrence 6 years after initial presentation. Histologically, all cases were composed of variably sized ectatic, thin-walled vessels lined by flat normochromic endothelium diffusely infiltrating mammary stroma. Where present, lesional vessels infiltrated between and around terminal duct lobular units but not into individual intralobular stroma. Most cases (6/8) showed a combination of lymphatic-appearing and haemangiomatous-appearing vessels. Lymphatic-appearing vessels were D2-40 positive in all but one case. D2-40 was negative or weak in haemangiomatous-appearing vessels. All lesional vessels were CD31 positive. Ki-67 indices were <1% in all but one case (5%). CONCLUSIONS: Mammary angiomatosis is a rare vascular lesion that shares clinical, morphological and immunohistochemical features with LGAS; however, certain key traits make the distinction possible.


Assuntos
Angiomatose/metabolismo , Antígenos de Neoplasias/análise , Doenças Mamárias/metabolismo , Neoplasias da Mama/química , Hemangiossarcoma/química , Imuno-Histoquímica , Imunofenotipagem/métodos , Molécula-1 de Adesão Celular Endotelial a Plaquetas/análise , Adulto , Angiomatose/patologia , Anticorpos Monoclonais Murinos , Biópsia , Doenças Mamárias/patologia , Neoplasias da Mama/patologia , Diagnóstico Diferencial , Feminino , Hemangiossarcoma/patologia , Humanos , Pessoa de Meia-Idade , Fenótipo , Valor Preditivo dos Testes , Prognóstico , Adulto Jovem
19.
Asian Pac J Cancer Prev ; 20(5): 1463-1470, 2019 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-31127909

RESUMO

Background: Due to lack of availability of gene expression profiling (GEP) for most developing countries and clinicians; the immunohistochemistry (IHC) is mostly used in the clinical application. The aim of our study is to check the possibility of using IHC to detect MYC and BCL2 in our patients with diffuse large B-cell lymphoma (DLBCL) instead of GEP to stratify them into high and low-risk groups. This will help in a proper treatment choice of subsequent improvement in the survival outcome. Method: During the study period, 90 DLBCL patients were eligible. MYC and BCL2 evaluated by IHC and gene rearrangement by real-time PCR (RT-PCR) and correlated with clinical-pathological features and survival. Results: Through IHC, the expression of MYC, BCL2, and double expression was detected in 35.6%, 46.7% and 30% of patients, respectively. While by RT-PCR, it was 4.53±0.74 for MYC compared with 2.18±0.78 for BCL-2. Most patients with BCL2+/MYC+; double-expressor and double-hit lymphomas (DEL and DHL) had high stage (III, IV), more extra-nodal involvement, (P value <0.001) and intermediate to high International Prognostic Index (IPI) risk profile (P-value <0.001). The median overall survival was 14 months and 6 months for DEL and DHL, respectively. While all patients with DHL died during the follow-up period, the median PFS were only 2 months for DEL. There was a statistically significant correlation between mRNA of MYC and BCL2 with their protein expression (p<0.001). Conclusion: Our results confirmed the unique characters and poor outcome associated with DEL and DHL mandated the need for more intense therapy and not the standard protocol. Moreover, the significant correlation between protein overexpression and gene rearrangement may open the door for the possibility to use IHC instead of RT-PCR in developing countries.


Assuntos
Linfoma Difuso de Grandes Células B/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-myc/genética , Translocação Genética/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imuno-Histoquímica/métodos , Imunofenotipagem/métodos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , Estudos Retrospectivos
20.
Int J Mol Sci ; 20(8)2019 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-31003463

RESUMO

Immunotherapy using immune checkpoints inhibitors has become the standard treatment for first and second line therapy in patients with non-small cell lung cancer (NSCLC). However, proper predictive factors allowing precise qualification of NSCLC patients for immunotherapy have not been developed so far. Expression of PD-L1 on tumor cells and tumor mutation burden are used in qualification of patients to first line therapy with pembrolizumab and atezolizumab in combination with ipilimumab in prospective clinical trials. Nevertheless, not all patients with these predictive factors benefit from immunotherapy. Major methodological difficulties in testing of these factors and in the interpretation of test results still exist. Therefore, other predictive factors are sought. Intensive research on the recognition of tumor immunophenotype and gut microbiome in NSCLC patients are underway. The first correlations between the effectiveness of immunotherapy and the intensity of inflammatory response in the tumor, microbiome diversity, and the occurrence of certain bacterial species in gut have been described. The purpose of our manuscript is to draw attention to factors affecting the efficacy of immunotherapy with anti-PD-L1 antibodies in NSCLC patients. Additional markers, for example TMB (tumor mutations burden) or microbiome profile, are needed to more accurately determine which patients will benefit from immunotherapy treatment.


Assuntos
Antígeno B7-H1/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Imunoterapia , Receptor de Morte Celular Programada 1/genética , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Imunofenotipagem/métodos , Ipilimumab/uso terapêutico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia
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