RESUMEN
The ability of CD8+ T lymphocytes to eliminate tumors is limited by their ability to engender an immunosuppressive microenvironment. Here we describe a subset of tumor-infiltrating CD8+ T cells marked by high expression of the immunosuppressive ATP ecto-nucleotidase CD39. The frequency of CD39highCD8+ T cells increased with tumor growth but was absent in lymphoid organs. Tumor-infiltrating CD8+ T cells with high CD39 expression exhibited features of exhaustion, such as reduced production of TNF and IL2 and expression of coinhibitory receptors. Exhausted CD39+CD8+ T cells from mice hydrolyzed extracellular ATP, confirming that CD39 is enzymatically active. Furthermore, exhausted CD39+CD8+ T cells inhibited IFNγ production by responder CD8+ T cells. In specimens from breast cancer and melanoma patients, CD39+CD8+ T cells were present within tumors and invaded or metastatic lymph nodes, but were barely detectable within noninvaded lymph nodes and absent in peripheral blood. These cells exhibited an exhausted phenotype with impaired production of IFNγ, TNF, IL2, and high expression of coinhibitory receptors. Although T-cell receptor engagement was sufficient to induce CD39 on human CD8+ T cells, exposure to IL6 and IL27 promoted CD39 expression on stimulated CD8+ T cells from human or murine sources. Our findings show how the tumor microenvironment drives the acquisition of CD39 as an immune regulatory molecule on CD8+ T cells, with implications for defining a biomarker of T-cell dysfunction and a target for immunotherapeutic intervention.Significance: The tumor microenvironment elicits a subset of functionally exhausted CD8+ T cells by creating conditions that induce cell surface expression of CD39, an immunosuppressive molecule that can be therapeutically targeted to restore effector T-cell function. Cancer Res; 78(1); 115-28. ©2017 AACR.
Asunto(s)
Antígenos CD/metabolismo , Apirasa/metabolismo , Linfocitos T CD8-positivos/metabolismo , Linfocitos Infiltrantes de Tumor/metabolismo , Adenosina Trifosfato/metabolismo , Animales , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/patología , Linfocitos T CD8-positivos/inmunología , Citocinas/metabolismo , Femenino , Humanos , Metástasis Linfática/inmunología , Metástasis Linfática/patología , Linfocitos Infiltrantes de Tumor/inmunología , Masculino , Melanoma/inmunología , Melanoma/patología , Ratones Endogámicos BALB C , Ratones Noqueados , Microambiente Tumoral/inmunología , Ensayos Antitumor por Modelo de XenoinjertoAsunto(s)
Carcinoma de Células de Merkel/patología , Carcinoma de Células Escamosas/patología , Metástasis Linfática/patología , Neoplasias Primarias Múltiples/patología , Neoplasias Cutáneas/patología , Carcinoma de Células de Merkel/inmunología , Carcinoma de Células Escamosas/inmunología , Humanos , Huésped Inmunocomprometido , Trasplante de Riñón , Metástasis Linfática/inmunología , Masculino , Persona de Mediana Edad , Neoplasias Primarias Múltiples/inmunología , Neoplasias Cutáneas/inmunologíaRESUMEN
ABSTRACT Objectives The presence of thyroglobulin (Tg) in needle washouts of fine needle aspiration biopsy (Tg-FNAB) in neck lymph nodes (LNs) suspected of metastasis has become a cornerstone in the follow-up of patients with papillary thyroid carcinoma (PTC). However, there are limited data regarding the measurement of anti-Tg antibodies in these washouts (TgAb-FNAB), and it is not clear whether these antibodies interfere with the assessment of Tg-FNAB or whether there are other factors that would more consistently justify the finding of low Tg-FNAB in metastatic LNs. Materials and methods We investigated 232 FNAB samples obtained from suspicious neck LNs of 144 PTC patients. These samples were divided according to the patient’s serum TgAb status: sTgAb- (n = 203 samples) and sTgAb+ (n = 29). The TgAb-FNAB levels were measured using two different assays. Tg-FNAB was also measured using two assays when low levels (< 10 ng/mL) were identified in the first assay of the metastatic LNs from the sTgAb+ samples. Results The TgAb-FNAB results were negative in both assays in all samples. Low levels of Tg-FNAB were identified in 11/16 of the metastatic LNs of the sTgAb+ patients and 16/63 of the sTgAb- patients (p < 0.05) using assay 1. The measurement of the Tg-FNAB levels using assay 2 indicated additional metastases in 5 LNs of the sTgAb+ patients. Conclusions Factors other than the presence of TgAb-FNAB may contribute to the higher number of metastatic LNs with undetectable Tg-FNAB in the sTgAb+ group. In addition, the measurement of Tg-FNAB using different assays was useful to enhance the diagnosis of metastatic LNs, particularly when cytological and Tg-FNAB results are discordant.
Asunto(s)
Humanos , Autoanticuerpos/sangre , Tiroglobulina/sangre , Neoplasias de la Tiroides/sangre , Carcinoma/sangre , Ganglios Linfáticos/inmunología , Valores de Referencia , Carcinoma/inmunología , Carcinoma/patología , Carcinoma Papilar , Fluoroinmunoensayo/métodos , Valor Predictivo de las Pruebas , Biopsia con Aguja Fina/instrumentación , Biopsia con Aguja Fina/métodos , Ganglios Linfáticos/patología , Metástasis Linfática/inmunología , Metástasis Linfática/patología , CuelloRESUMEN
OBJECTIVES: The presence of thyroglobulin (Tg) in needle washouts of fine needle aspiration biopsy (Tg-FNAB) in neck lymph nodes (LNs) suspected of metastasis has become a cornerstone in the follow-up of patients with papillary thyroid carcinoma (PTC). However, there are limited data regarding the measurement of anti-Tg antibodies in these washouts (TgAb-FNAB), and it is not clear whether these antibodies interfere with the assessment of Tg-FNAB or whether there are other factors that would more consistently justify the finding of low Tg-FNAB in metastatic LNs. MATERIALS AND METHODS: We investigated 232 FNAB samples obtained from suspicious neck LNs of 144 PTC patients. These samples were divided according to the patient's serum TgAb status: sTgAb- (n = 203 samples) and sTgAb+ (n = 29). The TgAb-FNAB levels were measured using two different assays. Tg-FNAB was also measured using two assays when low levels (< 10 ng/mL) were identified in the first assay of the metastatic LNs from the sTgAb+ samples. RESULTS: The TgAb-FNAB results were negative in both assays in all samples. Low levels of Tg-FNAB were identified in 11/16 of the metastatic LNs of the sTgAb+ patients and 16/63 of the sTgAb- patients (p < 0.05) using assay 1. The measurement of the Tg-FNAB levels using assay 2 indicated additional metastases in 5 LNs of the sTgAb+ patients. CONCLUSIONS: Factors other than the presence of TgAb-FNAB may contribute to the higher number of metastatic LNs with undetectable Tg-FNAB in the sTgAb+ group. In addition, the measurement of Tg-FNAB using different assays was useful to enhance the diagnosis of metastatic LNs, particularly when cytological and Tg-FNAB results are discordant.
Asunto(s)
Autoanticuerpos/sangre , Carcinoma/sangre , Ganglios Linfáticos/inmunología , Tiroglobulina/sangre , Neoplasias de la Tiroides/sangre , Biopsia con Aguja Fina/instrumentación , Biopsia con Aguja Fina/métodos , Carcinoma/inmunología , Carcinoma/patología , Carcinoma Papilar , Fluoroinmunoensayo/métodos , Humanos , Ganglios Linfáticos/patología , Metástasis Linfática/inmunología , Metástasis Linfática/patología , Cuello , Valor Predictivo de las Pruebas , Valores de Referencia , Reproducibilidad de los Resultados , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides/inmunología , Neoplasias de la Tiroides/patología , UltrasonografíaRESUMEN
BACKGROUND: Deficient immune response in the cervical lymph nodes of patients with head and neck squamous cell carcinoma may contribute to dissemination of metastatic neoplastic cells. This study evaluates the immune response in cervical lymph nodes from patients with primary oral cavity squamous cell carcinoma (OCSCC). METHODS: The density of immature (CD1a(+)) and mature (CD83(+)) dendritic cells (DCs), cytotoxic T lymphocytes CD8(+) /perforin(+) (CTLs), and Foxp3(+) regulatory T (Tregs) cells in the lymph nodes of patients with OCSCC without cervical lymph node metastases (LN1) (negative) (n = 10) were identified through immunohistochemistry. From patients with cervical lymph node metastases, samples were obtained of lymph nodes both with (LM2) (positive) (n = 10) and without (LN2) (negative) (n = 10) metastases. RESULTS: The results demonstrated that the number of CD1a(+) and Foxp3(+) cells was significantly higher in the LM2 group than in either the LN1 or the LN2 group. In addition, the number of CD8(+) /perforin(+) and CD83(+) cells was significantly lower in the LM2 group than in the other groups. CONCLUSION: The results of this study demonstrate a higher density of immature DCs and Tregs cells and a lower density of mature DCs and activated CTLs in metastatic than in non-metastatic lymph nodes. These findings might indicate an immunosuppressive microenvironment, which could be involved in the spread of neoplastic cells to cervical lymph nodes.
Asunto(s)
Carcinoma de Células Escamosas/inmunología , Ganglios Linfáticos/inmunología , Neoplasias de la Boca/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD/análisis , Antígenos CD1/análisis , Antígenos CD8/análisis , Linfocitos T CD8-positivos/inmunología , Carcinoma de Células Escamosas/patología , Recuento de Células , Células Dendríticas/inmunología , Femenino , Estudios de Seguimiento , Factores de Transcripción Forkhead/análisis , Humanos , Tolerancia Inmunológica/inmunología , Inmunoglobulinas/análisis , Metástasis Linfática/inmunología , Metástasis Linfática/patología , Activación de Linfocitos/inmunología , Masculino , Glicoproteínas de Membrana/análisis , Persona de Mediana Edad , Neoplasias de la Boca/patología , Cuello , Perforina , Proteínas Citotóxicas Formadoras de Poros/análisis , Estudios Retrospectivos , Linfocitos T Citotóxicos/inmunología , Linfocitos T Reguladores/inmunología , Microambiente Tumoral/inmunología , Adulto Joven , Antígeno CD83RESUMEN
OBJECTIVE: To evaluate and characterize macrophage populations (M1/M2) in the tumor microenvironment of oral cavity squamous cell carcinoma (OCSCC). The relationship between macrophages and clinicopathological factors, such as survival data, lymph node metastasis, tumoral proliferation, and WHO histological grading are also analyzed. MATERIALS AND METHODS: The samples consisted of surgically excised specimens from patients with non-metastatic and metastatic OCSCC and normal oral mucosa (control). Immunohistochemistry, flow cytometry, and qRT-PCR were used to evaluate macrophage populations and the expression of pro- (IL-12, IL-23, and INF-γ) and anti-inflammatory (IL-10 and TGF-ß) cytokines. The level required for statistical significance was defined as p<0.05. RESULTS: The data showed a predominance of M2 phenotype (high percentage of IL-10(+)TGF-ß(+)) macrophages in the tumor microenvironment of OCSCC. A higher percentage of macrophages expressing TGF-ß was seen in the OCSCC group when compared with healthy individuals. The assessment of mRNA expression also presented a greater expression of anti-inflammatory cytokines TGFß and IL10 in OCSCC when compared with the control group. The percentage of macrophages, demonstrated by immunohistochemistry, was significantly higher in the metastatic OCSCC group than in the non-metastatic and control groups. The log-rank test also showed that the mean survival time for patients with high levels of macrophages was less (44 months) when compared with patients with a low percentage of such cells (93 months). CONCLUSION: A predominance of the M2 phenotype in the tumor microenvironment of OCSCC could contribute to local immunosuppression, via TGF-ß production, and consequently greater lymph node involvement and reduced patient survival time.
Asunto(s)
Carcinoma de Células Escamosas/inmunología , Citocinas/análisis , Mediadores de Inflamación/análisis , Macrófagos/inmunología , Neoplasias de la Boca/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD11/análisis , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/secundario , Recuento de Células , Proliferación Celular , Femenino , Estudios de Seguimiento , Humanos , Tolerancia Inmunológica/inmunología , Interferón gamma/análisis , Interleucina-10/análisis , Interleucina-12/análisis , Interleucina-23/análisis , Metástasis Linfática/inmunología , Metástasis Linfática/patología , Macrófagos/clasificación , Macrófagos/patología , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/patología , Clasificación del Tumor , Invasividad Neoplásica , Estudios Retrospectivos , Tasa de Supervivencia , Factor de Crecimiento Transformador beta/análisis , Microambiente Tumoral/inmunologíaRESUMEN
The purpose of this study was to characterize and quantify cells involved in immune response in metastasis-free regional lymph nodes (RLNs) draining different human epithelial tumors and compare them (by immunohistochemistry) with control lymph nodes from patients with non malignant diseases. We showed that T cells number was decreased in RLNs as compared to the controls with reduction in both CD4+ T cells and CD8+ T cells subsets and an inverted ratio (CD4+: CD8+). B lymphocytes and follicular dendritic cells were decreased with respect to the controls. S100+ dendritic cells (DCs) and mature DCs were detected in T dependent areas. Their mean number was significantly lower as compared to control. Immature DCs were significantly diminished compared to RLN and control nodes. CD57+ cells, follicular T helper cells and/or NK cells, were localized in the clear zone of germinal centres and their mean number was significantly increased. There were no CD57+ cells in hypoplastic follicles. In this study we show that RLNs draining human cancer present reduction in almost all immune cells, except CD57+ cells. These findings may be related to the deficient anti-tumor immune response in patients with cancer and subsequent tumor progression.
El objetivo del trabajo fue caracterizar y cuantificar utilizando inmuno-histoquímica, las células involucradas en la respuesta inmune en ganglios linfáticos regionales (GLRs) que drenan distintos tumores epiteliales malignos humanos y compararlas con ganglios controles (GLCs) provenientes de pacientes sin enfermedad neoplásica maligna. Determinamos que los GLRs presentaban una marcada depleción de linfocitos B y T, células dendríticas (CD) foliculares y CD interdigitantes maduras respecto a los controles. En los linfocitos T, además de estar disminuidos, se observó una inversión de la relación T CD4+: T CD8+, a favor de los T CD8+. La depleción de CD inmaduras fue mayor respecto a las maduras. Las células CD57+, células foliculares T helper y/o células NK, localizadas en las zonas claras de los centros germinativos, presentaron un marcado incremento en los GLRs comparados con los GLCs, excepto en los casos de ganglios linfáticos con folículos hipoplásicos. En este estudio, demostramos que los GLRs que drenan carcinomas humanos presentan una significativa reducción en casi todas las células de la respuesta inmune, excepto las células NK. Estos hallazgos podrían estar relacionados con la deficiente respuesta antitumoral de los pacientes con cáncer y la subsiguiente progresión tumoral.
Asunto(s)
Adulto , Anciano , Humanos , Persona de Mediana Edad , Células Dendríticas/citología , Células Dendríticas/inmunología , Ganglios Linfáticos/inmunología , Subgrupos Linfocitarios/inmunología , Neoplasias/inmunología , Linfocitos T/citología , Linfocitos B/inmunología , Estudios de Casos y Controles , Inmunidad Celular , Ganglios Linfáticos/patología , Metástasis Linfática/inmunología , Metástasis Linfática/patología , Neoplasias/patología , Linfocitos T/inmunologíaRESUMEN
The purpose of this study was to characterize and quantify cells involved in immune response in metastasis-free regional lymph nodes (RLNs) draining different human epithelial tumors and compare them (by immunohistochemistry) with control lymph nodes from patients with non malignant diseases. We showed that T cells number was decreased in RLNs as compared to the controls with reduction in both CD4+ T cells and CD8+ T cells subsets and an inverted ratio (CD4+: CD8+). B lymphocytes and follicular dendritic cells were decreased with respect to the controls. S100+ dendritic cells (DCs) and mature DCs were detected in T dependent areas. Their mean number was significantly lower as compared to control. Immature DCs were significantly diminished compared to RLN and control nodes. CD57+ cells, follicular T helper cells and/or NK cells, were localized in the clear zone of germinal centres and their mean number was significantly increased. There were no CD57+ cells in hypoplastic follicles. In this study we show that RLNs draining human cancer present reduction in almost all immune cells, except CD57+ cells. These findings may be related to the deficient anti-tumor immune response in patients with cancer and subsequent tumor progression.
Asunto(s)
Células Dendríticas/citología , Células Dendríticas/inmunología , Ganglios Linfáticos/inmunología , Subgrupos Linfocitarios/inmunología , Neoplasias/inmunología , Linfocitos T/citología , Adulto , Anciano , Linfocitos B/inmunología , Estudios de Casos y Controles , Humanos , Inmunidad Celular , Ganglios Linfáticos/patología , Metástasis Linfática/inmunología , Metástasis Linfática/patología , Persona de Mediana Edad , Neoplasias/patología , Linfocitos T/inmunologíaRESUMEN
La detección histológica de metástasis en los ganglios linfáticos axilares es un parámetro de mayor valor pronóstico en cáncer de mama. Un 30 por ciento de pacientes con ganglios linfáticos negativos tienen recaída en cinco años, sugiriendo que, este estudio no es suficiente para detectar todas la metástasis. En el presente estudio, se determinó la expresión de marcadores mamoglobina y MAGE-A3. en ganglios axilares histológicamente negativos de pacientes con cáncer de mama, mediante reacción en cadena polimerasa transcriptasa-reversa, a fin de detectar células tumorales aisladas o micrometástasis. La expresión mamoglobina y MAGE-A3 se detectaron en 55,6 por ciento y 33,3 por ciento, respectivamente. Se amplificó el ARN de mamoglobina y MAGE-A3 en ganglios histológicamente positivos en un 72,7 por ciento y 54,5 por ciento, respectivamente. Se relacionó la presencia o ausencia de células tumorales en ganglios negativos con tamaño tumoral, grado histológico, émbolos neoplásicos vasculares, obteniendo resultados no concluyentes, no se logró distribución equitativa de las muestras. Estos resultados muestran que la mamoglobina y MAGE-A3 son útiles para detección de células tumorales aisladas en ganglios axilares negativos.
Histological detection of metastasis in axillary lymph nodes is a current practice, and the parameter has greatest prognostic value in breast cancer. 30 per cent of negative lymph nodes patients at histology studies has disease relapse in five years, suggesting that this nethod is inadequate to identify all cases with metastasis. In this study, the expression of mammaglobin and MAGE-A3 markers were determined in histological negative axillaries lymph nodes brest cancer patients, by reverse transcriptase polymerase chain reaction. The expression mammaglobin and MAGE-A3 were detected in 55.6 per cent and 33.3 per cent, respectively. The ARN of mammaglobin and MAGE-A3 was amplified in patients with histological positive axilaries lymph nodes, obtaining an expression of 72,7 percent and 54,5 per cent, respectively. Finally, presence or absence of tumour cells detected in negative lymph nodes were related to tumour seze, histological grade, vascular tumour emboli; non conclusive results were obtaining because it wasn't possible to obtain an equitable distribution of the samples. These results show that mammaglobin and MAGE-A3 are useful for detection of isolated tumour cells in axilar node negative.
Asunto(s)
Humanos , Femenino , Ganglios Linfáticos/anatomía & histología , Metástasis Linfática/inmunología , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/patología , Adenocarcinoma/patología , Axila , Biopsia/métodos , Carcinoma Ductal de Mama/patología , Oncología MédicaRESUMEN
BACKGROUND: The role of immune system in the pathogenesis and progression of breast cancer is a subject of controversy, and this stimulated us to investigate the association of the immunophenotype of tumor-infiltrating lymphocytes in early breast cancer with the spread of tumor cells to axillary lymph nodes. METHODS: Tumor samples from 23 patients with early breast cancer from the Department of Gynecology and Obstetrics of Ribeirão Preto Medical School (USP) were obtained at the time of biopsy and submitted to an enzyme-digestion procedure for the extraction of tumor-infiltrating lymphocytes. The lymphocytes extracted were analyzed by dual-color flow cytometry with monoclonal antibodies in these combinations: CD3 FITC/CD19 PE, CD3 FITC/CD4 PE, CD3 FITC/CD8 PE, and CD16/56 PerCP, which are specific for immunophenotyping of T and B lymphocytes, helper and cytotoxic T lymphocytes, and natural killer (NK) cells. The mean percentage of these cells was used for comparing groups of patients with or without lymph node metastasis. RESULTS: The mean value for T-lymphocyte infiltration was 24.72 +/- 17.37%; for B-lymphocyte infiltration, 4.22 +/- 6.27%; for NK-cell infiltration, 4.41 +/- 5.22%, and for CD4(+) and CD8(+) T-lymphocyte infiltration, 12.43 +/- 10.12% and 11.30 +/- 15.09%, respectively. Only mean values of T- and CD4(+) T-lymphocyte infiltration were higher in the group of patients with lymph node metastasis, while no differences were noted in the other lymphocyte subpopulations. CONCLUSION: The association of tumor-infiltrating CD4(+) T lymphocytes with lymph node metastasis suggests a role for these cells in the spread of neoplasia to lymph nodes in patients with early breast cancer.
Asunto(s)
Neoplasias de la Mama/inmunología , Linfocitos T CD4-Positivos/inmunología , Ganglios Linfáticos/patología , Subgrupos Linfocitarios/inmunología , Linfocitos Infiltrantes de Tumor/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales , Axila , Neoplasias de la Mama/patología , Linfocitos T CD4-Positivos/patología , Femenino , Citometría de Flujo , Humanos , Inmunofenotipificación , Metástasis Linfática/inmunología , Metástasis Linfática/patología , Subgrupos Linfocitarios/patología , Linfocitos Infiltrantes de Tumor/patología , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de NeoplasiasRESUMEN
INTRODUÇÃO: O papel do sistema imunológico na patogênese e progressão do câncer de mama ainda é controverso, e isto nos estimulou a verificar a associação do imunofenótipo dos linfócitos tumor infiltrantes do câncer de mama inicial com a disseminação de células tumorais para os linfonodos axilares. MÉTODOS: Amostras tumorais de 23 pacientes com câncer de mama inicial do Departamento de Ginecologia e Obstetrícia da Faculdade de Medicina de Ribeirão Preto (USP) foram obtidas no momento da biópsia e depois submetidas ao método de digestão enzimática para a extração dos linfócitos tumor infiltrantes. Os linfócitos extraídos foram analisados por citometria de fluxo com anticorpos monoclonais nas seguintes combinações: CD3 FITC/CD19 PE, CD3 FITC/CD4 PE, CD3 FITC/CD8 PE, e CD16/56 PerCP, específicos para imunofenotipagem de linfócitos T e B, linfócitos T helper, linfócitos citotóxicos, e células Natural Killer. Os valores médios destas subpopulações leucocitárias foram comparados entre grupos de pacientes com ou sem metástases linfonodais. RESULTADOS: O valor médio do infiltrado por linfócitos T foi 24,72±17,37%, para o infiltrado por linfócitos B foi 4,22±6,27%, e para o infiltrado por células Natural Killer foi 4,41±5,22%, e para o infiltrado por linfócitos T CD4+ e CD8+ foram, respectivamente, 12,43±10,12% e 11,30±15,09%. Os valores médios do infiltrado por células T e T CD4+ foram maiores no grupo de pacientes com metástase axilar, enquanto nas outras subpopulações nada foi encontrado.CONCLUSÃO: A associação dos linfócitos T CD4+ tumor infiltrantes com metástases linfonodais sugere um papel destas células na disseminação das células neoplásicas aos linfonodos dos pacientes com câncer de mama inicial.
Asunto(s)
Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Persona de Mediana Edad , Neoplasias de la Mama/inmunología , /inmunología , Ganglios Linfáticos/patología , Subgrupos Linfocitarios/inmunología , Linfocitos Infiltrantes de Tumor/inmunología , Anticuerpos Monoclonales , Axila , Neoplasias de la Mama/patología , /patología , Citometría de Flujo , Inmunofenotipificación , Metástasis Linfática/inmunología , Metástasis Linfática/patología , Subgrupos Linfocitarios/patología , Linfocitos Infiltrantes de Tumor/patología , Invasividad Neoplásica , Estadificación de NeoplasiasRESUMEN
O carcinoma de células escamosas (CCE figura entre aslesões de maior interesse da região bucal e quando presente em língua exibe aspecto mais infiltrativo, curso clínico agressivo e prognóstico desfavorável, o que pode estar associado com maior potencial metastático. O presente trabalho investigou a expressão da B-catenina, metaloproteinase-7 (MMP-7) e da 26 (MMP-26) em CCE de língua e divididos em dois grupos: grupo metástico (n=12) e grupo sem metástase (n=12) os quais foram submetidos a marcação imunohistoquímica. Realizou-se uma análise semi-quantitativa no fronte invasivo tumoral e a imunoexpressão das proteínas foi categorizada como sendo negativa, positiva e fortemente positiva, atribuindo-se escores, 0 + e ++, respectivamente. A expressão para B-catenina demonstrou que 33 por cento dos casos foram escore "0", 50 por cento escore "+" e 17 por cento escore "++" no grupo metastatico; 42 por cento com escore "0", 33 por cento escore "+" e 25 por cento escore "++" no grupo sem metástase. Alem disso, a B-catenina demonstrou marcação ora restrita à membrana ora citoplasmática ou nuclear e, ainda, associação destas. Com relação à MMP-7, os resultados demonstraram padrão de marcaço idêntico nos dois grupos, onde 17 por cento dos casos exibiram escore "0, 50 por cento "+" e 33 por cento "++". Tratando-se de MMP-26, observaram-se 25 por cento com escore "0", 8 por cento "+" e 67 por cento escore "++" no grupo metatástico; 8 por cento com escore "0", 50 por cento "+" e 42 por cento escore "++" no grupo sem metástase. A análise estatística através dos testes U de Mann e Whitney e correlação de Spearmam não demonstrou nunhuma diferença significativa entre a expressão das proteínas nos dois grupos e, tampouco, correlação entre a expressão das mesmas. Diante destes dados, conclui-se que a expressão da B-catenina, MMP-7 e MMP-26 não constitui um método eficaz isolado para predizer o potencial metastatico dos CCE em língua
Asunto(s)
Humanos , Carcinoma de Células Escamosas/inmunología , Carcinoma de Células Escamosas , Inmunohistoquímica , Lengua/inmunología , Metaloproteinasa 7 de la Matriz , Metástasis Linfática/inmunología , Neoplasias de la Boca , Neoplasias de la Lengua , Estadísticas no ParamétricasRESUMEN
Linfonodos obtidos de espécimes de linfadenectomia de pacientes portadores de melanoma cutâneo foram analisados em seu padräo reacional, sob duas formas distintas de abordagem. Na primeira, através da utilizaçäo de métodos convencionais de estudo histológico e avaliaçäo subjetiva do seu grau de reatividade, aliados a análise estatística, buscou-se principalmente investigar o efeito da proximidade dos linfonodos em relaçäo ao sítio do tumor primário na intensidade da resposta das áreas T e B-dependentes, além da presença de histiocitose sinusal. Além disso, foi pesquisada a possível influência da presença de metástases e de aspectos relacionados à área de excisäo cirúrgica do tumor primário, como a existência de tumor residual, de alteraçöes decorrentes de cicatrizaçäo cutânea anormal e de parâmetros clínicos e patológicos que influem no prognóstico do melanoma humano. A caracterizaçäo da posiçäo dos linfonodos em relaçäo ao tumor primário foi feita através de técnica de injeçäo de corante azul que permite a identificaçäo do linfonodo "sentinela" ou proximal. O grau de reatividade foi estimado através de avaliaçäo subjetiva, convertida numericamente para fins estatísticos. Observou-se basicamente que graus diferentes de reatividade, inicialmente notados entre os linfonodos proximais e os demais linfonodos ao longo da corrente linfática, podem estar relacionados ao local anatômico da cadeia linfonodal, como mostrado pela baixa reatividade paracortical dos linfonodos inguinais e pela reaçäo folicular mais intensa nos linfonodos cervicais. Dos aspectos ligados à área do tumor primário, apenas a presença de ulceraçäo e de sinais de regressäo no melanoma mostraram correlaçäo com a intensidade da reaçäo paracortical. Na segunda abordagem, foram investigadas as populaçöes celulares dos linfonodos, em especial as células dendríticas do paracórtex, como indicadoras do seu estado reacional e realizadas medidas objetivas do grau de expansäo paracortical, através do emprego de métodos imunocitoquímicos e de análise computadorizada de imagens. Os resultados mais importantes se relacionam ao encontro de sinais de modulaçäo morfológica e imunofenotípica pelas células dendríticas paracorticais, caracterizada basicamente pelo aparecimento e grau de complexidade dos dendritos, pela expressäo diferenciada de dois antígenos, a proteína S-100 e o antígeno HLA-DR, e pela distribuiçäo das células no nódulo paracortical. A caracterizaçäo destes aspectos pode representar a demonstraçäo in situ do estado funcional destas células no nódulo paracortical reativo, bem como no paracórtex convencionalmente considerado näo-reativo...