RESUMO
Papillary thyroid cancer (PTC), whose incidence has been increasing in the last years, occurs more frequently in women. Experimental studies suggested that estrogen could be an important risk factor for the higher female incidence. In fact, it has been demonstrated that 17ß-estradiol (E2) could increase proliferation and dedifferentiation in thyroid follicular cells. Genomic estrogen responses are typically mediated through classical estrogen receptors, the α and ß isoforms, which have been described in normal and abnormal human thyroid tissue. Nevertheless, effects mediated through G protein estrogen receptor 1 (GPR30/GPER/GPER1), described in some thyroid cancer cell lines, could be partially responsible for the regulation of growth in normal cells. In this study, GPER1 gene and protein expression are described in non-malignant and in papillary thyroid cancer (PTC), as well as its association with clinical features of patients with PTC. The GPER1 expression was lower in PTC as compared to paired non-malignant thyroid tissues in fresh samples of PTC and in silico analysis of GEO and TCGA databases. In PTC cases of TCGA database, low GPER1 mRNA expression was independently associated with metastatic lymph nodes, female gender, and BRAF mutation. Besides, GPER1 mRNA levels were positively correlated with mRNA levels of thyroid differentiation genes. These results support the hypothesis that GPER1 have a role in PTC tumorigenesis and might be a potential target for its therapy. Further studies are needed to determine the functionality of these receptors in normal and diseased thyroid.
Assuntos
Biologia Computacional/métodos , Regulação para Baixo , Receptores de Estrogênio/genética , Receptores Acoplados a Proteínas G/genética , Câncer Papilífero da Tireoide/genética , Neoplasias da Glândula Tireoide/genética , Estudos de Casos e Controles , Bases de Dados Genéticas , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , Masculino , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Caracteres SexuaisRESUMO
The incidence of papillary thyroid carcinoma (PTC) has been increasing, which raised the interest in its molecular pathways. Although the high expression of ecto-5'-nucleotidase (NT5E) gene expression and NT5E enzymatic activity in several types of cancer is associated with tumor progression, its role in PTC remains unknown. Here, we investigated the AMP hydrolysis in human normal thyroid cells and PTC cells, in primary culture, and the association of NT5E expression with clinical aspects of PTC patients. AMPase activity was higher in thyroid cells isolated from PTC, as compared to normal thyroid (Pâ¯=â¯0.0063). Significant correlation was observed between AMPase activity and NT5E levels in primary thyroid cell cultures (râ¯=â¯0.655, Pâ¯=â¯0.029). NT5E expression was higher in PTC than in the adjacent non-malignant thyroid tissue (Pâ¯=â¯0.0065) and were positively associated with metastatic lymph nodes (Pâ¯=â¯0.0007), risk of recurrence (Pâ¯=â¯0.0033), tumor size (Pâ¯=â¯0.049), and nodular hyperplasia in the adjacent thyroid parenchyma, when compared to normal thyroid or lymphocytic thyroiditis (Pâ¯=â¯0.0146). After adjusting for potential confounders, the malignant/non-malignant paired expression ratio of NT5E mRNA was independently associated with metastatic lymph nodes (Pâ¯=â¯0.0005), and tumor size (P=0.0005). In addition, the analysis of PTC described in the TCGA database also showed an association between higher expression of NT5E and metastatic lymph nodes, and tumor microinvasion. These results support the hypothesis that NT5E have a role in PTC microenvironment and might be a potential target for PTC therapy.
Assuntos
5'-Nucleotidase/metabolismo , Linfonodos/enzimologia , Linfonodos/patologia , Metástase Linfática/patologia , Câncer Papilífero da Tireoide/enzimologia , Câncer Papilífero da Tireoide/patologia , 5'-Nucleotidase/genética , Linhagem Celular Tumoral , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Nucleotidases/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Câncer Papilífero da Tireoide/genética , Glândula Tireoide/patologiaRESUMO
Os carcinomas sarcomatóides de bexiga são neoplasias raras, representando apenas 0,3 por cento das patologias malignas da bexiga. Por apresentarem marcado grau de malignidade e agressividade, devem ser sempre consideradas no diagnóstico diferencial dos tumores da bexiga. Os autores revisam a literatura e relatam o caso de um paciente de 62 anos de idade, branco e tabagista, com queixa de hematúria macroscópica, investigada por cistocopia e biópsia. Um exame histológico do tumor sugeriu carcinoma sarcomatóide de bexiga. O diagnóstico foi confirmado por um exame imunohistoquímico. Como o paciente apresentava severa disfunção ventilatória, foi tratado com ressecção transuretral do tumor, recusou a indicação de terapia adjuvante evoluindo para óbito 5 meses após o diagnóstico
