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
PURPOSE: We evaluated the influence of koilocytosis, and other clinical and pathological variables in the risk of groin metastasis and death in penile cancer patients. MATERIALS AND METHODS: From January 1994 to January 2004, 172 patients with squamous cell carcinoma of the penis were treated at a single cancer center. Of these patients 144 were retrospectively studied to analyze prognostic factors and establish the role of koilocytosis in penile cancer. Univariate and multivariate analyses were performed, and Kaplan-Meier survival curves were generated. RESULTS: A total of 102 patients (71%) underwent groin dissection, of whom 84 (58.3%) had inguinal metastasis. Koilocytosis was present in 91 patients (63.1%) and it was associated with low and moderate primary tumor grade on univariate analysis (p = 0.0005). Although koilocytosis statistically correlated with Jackson stage (p = 0.017) and tumor grade (p = 0.002), it had no impact on disease specific survival (p = 0.912). Metastatic inguinal disease correlated with patient age, Jackson and disease specific survival. Only Jackson stage and inguinal relapse after groin dissection influenced overall survival on multivariate analysis (each p = 0.001). CONCLUSIONS: According to all studied variables only patient age and Jackson stage correlated with an increased risk of groin disease. Koilocytosis was rarely found in high grade penile tumors and it did not correlate with a high risk of metastatic groin disease or death.
