RESUMO
A common mutation in the BRAF gene, comprising the T1799A nucleotide transversion, which leads to the V600E amino acid substitution in the BRAF protein, has been observed in about 50% of papillary thyroid carcinomas (PTCs). However, BRAF protein expression has been rarely examined in such tumors. Clinical studies have shown important associations between BRAF mutation and clinical parameters in PTC, such as progression, invasion, and recurrence. The aim of this study was to evaluate the association between BRAF protein overexpression and the BRAF V600E mutation in a group of PTC patients. The study group included 116 patients with PTC from Araújo Jorge Hospital, Goiânia, Goiás, Brazil. Immunohistochemistry was utilized to analyze BRAF protein expression. Presence of the BRAF V600E mutation was determined by polymerase chain reaction amplification and restriction fragment length polymorphism, and confirmed by direct sequencing. The chi-square test with Yates correction and the Fisher exact test were used for statistical analysis. BRAF overexpression was detected in 55 patients with PTC (47.4%) and the BRAF V600E mutation was observed in 74 patients (63.8%). In the studied group, significant associations were observed between the BRAF V600E mutation and BRAF protein overexpression (P = 0.0115), and also between BRAF overexpression and extra-thyroid extension of the tumor (P = 0.0111). This study demonstrated a significant association between BRAF overexpression and the BRAF V600E mutation in PTC, highlighting the importance of these molecular events in the process of PTC carcinogenesis.
Assuntos
Substituição de Aminoácidos , Carcinoma/genética , Mutação Puntual , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias da Glândula Tireoide/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Sequência de Bases , Carcinoma/patologia , Carcinoma/cirurgia , Carcinoma Papilar , Análise Mutacional de DNA , Feminino , Expressão Gênica , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Estudos Retrospectivos , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgiaRESUMO
BRAF V600E is the most common mutation in cutaneous melanomas, and has been described in 30-72% of such cases. This mutation results in the substitution of valine for glutamic acid at position 600 of the BRAF protein, which consequently becomes constitutively activated. The present study investigated the BRAF V600E mutation frequency and its clinical implications in a group of 77 primary cutaneous melanoma patients treated in a cancer reference center in Brazil. Mutation analysis was accomplished by polymerase chain reaction, restriction fragment length polymorphism, and automated DNA sequencing. The chi-squared and Fischer exact tests were used for comparative analyses. The BRAF V600E mutation was detected in 54/77 (70.1%) melanoma subjects. However, no statistically significant association was found between the presence of the mutation and clinical or prognostic parameters. Our results demonstrated that the BRAF V600E mutation is a common event in melanomas, representing an important molecular target for novel therapeutic approaches in such tumors.
Assuntos
Melanoma/genética , Terapia de Alvo Molecular , Mutação/genética , Proteínas Proto-Oncogênicas B-raf/genética , Idoso , Brasil , Feminino , Humanos , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Polimorfismo de Nucleotídeo Único , Neoplasias Cutâneas , Melanoma Maligno CutâneoRESUMO
A interação do genoma do HPV com o genoma da célula hospedeira ou de proteínas virais com proteínas celulares necessárias ao controle do ciclo celular desencadeia a morte celular ou age como fator de iniciação e progressão de processos malignos. Diversostrabalhos têm sido desenvolvidos no sentido de associar a infecção de HPV aos cânceres de cabeça e pescoço. O objetivo do presente estudo foi comparar a detecção do genoma de HPV em pacientes com CEC da laringe, considerando os ensaios de PCR convencional e em tempo real. O grupo amostral foi constituído de 15 pacientes do Registro de Câncer de Base Populacional da ACCG. Das peças cirúrgicas, foi obtido DNA total, usado na investigação molecular, para detecção do genoma de HPV, utilizando os primers genéricos GP05/06, que detectam todos os tipos de HPV. O genoma de HPV foi amplificado em 30 dos casos por PCR convencional e no ensaio de PCR em tempo real apresentaram amplificação em 46,7 das amostras, evidenciando uma diferença em 40 . Os estudosde associação entre o HPV e os cânceres da laringe são importantes no sentido de ampliar o conhecimento acerca dos mecanismos de infecção, iniciação e promoção tumoral potencializada por estes vírus.
