RESUMO
Breast cancer (BC) is a disease with different clinical, histological and molecular characteristics, frequently presenting mutated tumour-suppressing genes and oncogenes. P53 is a known tumour suppressor that is often mutated in BC; several mutations in p53 inhibit its role as a transcriptional repressor of several oncogenes. Topoisomerase 2α (TOP2α) is a gene target of p53, and it is also a known target for anthracyclines. The aim of the present study, was to analyse the genetic alterations of p53 and TOP2α genes and their levels of protein expression, as well as their association with survival in Mexican women with BC. A total of 102 biopsies were collected (tumour and adjacent tissues) from patients with BC. To identify point mutations and deletions in the p53 gene, the Sanger sequencing method was carried out. Deletions or amplifications for TOP2α gene were determined using quantitative polymerase chain reaction (qPCR). In addition, the expression of the TOP2α and p53 proteins was evaluated by western blotting. Furthermore, p53 protein expression was analysed by proximity ligation assay (PLA)-qPCR. Only 28.5% of the patients were found to have triple-negative breast cancer (TNBC); the average age at the time of diagnosis of these patients was 50 years, and Scarff-Bloom-Richardson (SBR) histological grade III (p=0.0089). No differences in point mutations or deletions in p53, and deletions or amplifications as well as protein expression level of TOP2α were observed between patients with TNBC and non-TNBC patients. However, patients with TNBC showed p53 protein overexpression as determined by PLA-qPCR and western blotting (p<0.0001). Furthermore, we found an association between TOP2α amplification and overexpression of its protein in patients with TNBC (p<0.0001). Concerning p53, overexpression resulted in a lower survival in patients with BC.
Assuntos
Antígenos de Neoplasias/genética , DNA Topoisomerases Tipo II/genética , Proteínas de Ligação a DNA/genética , Análise de Sequência de DNA/métodos , Neoplasias de Mama Triplo Negativas/patologia , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Regulação para Cima , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Neoplasias/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , DNA Topoisomerases Tipo II/metabolismo , Proteínas de Ligação a DNA/metabolismo , Feminino , Amplificação de Genes , Regulação Neoplásica da Expressão Gênica , Humanos , México , Pessoa de Meia-Idade , Prognóstico , Análise de Sobrevida , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismoRESUMO
Abnormal expression and promoter methylation of microRNAs (miRNAs) are common events during cervical carcinogenesis. Worldwide, infection by types 18 and 16 of human papillomaviruses (HPVs) is considered the major risk factor for cervical cancer development. It has been reported that expression of the miRNAs can be deregulated by specific HPV genotypes. In this study we analyzed the promoter methylation of 22 miRNAs and the expression of three miRNAs in 10 non-squamous intraepithelial lesions (Non-SIL) without HPV16 infection, and 7 Non-SIL, 16 low-grade SIL (LSIL) and 16 cervical cancer samples, all with HPV16 infection. The methylation status was determined using Human Cancer miRNA EpiTect Methyl II Signature PCR Array® and the expression of miR-124, miR-218 and miR-193b was determined by qRT-PCR using individual TaqMan assays. Comparisons of groups defined were performed using the Fisher exact test for categorical variables and Mann-Whitney test for continuous variables. A p-value of <0.05 was considered statistically significant. The methylation levels of miR-124-2, miR-218-1, miR-218-2 and miR-34b/c promoters were significantly higher in cervical cancer than in LSIL samples. The methylation levels of miR-193b promoter were significantly lower in cervical cancer than in LSIL samples. The expression of miR-124 and miR-218 was significantly lower in cervical cancer than in LSIL samples. The expression of miR-193b was significantly higher in cervical cancer than in LSIL and Non-SIL samples. Our results suggest that the abnormal promoter methylation and expression of miR-124, miR-218 and miR-193b are common events during cervical carcinogenesis.
Assuntos
Metilação de DNA , Perfilação da Expressão Gênica/métodos , MicroRNAs/genética , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Infecções por Papillomavirus/genética , Displasia do Colo do Útero/genética , Neoplasias do Colo do Útero/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Regulação Neoplásica da Expressão Gênica , Papillomavirus Humano 16/patogenicidade , Humanos , Pessoa de Meia-Idade , Regiões Promotoras Genéticas , Adulto JovemRESUMO
El tumor fibroso solitario es un tumor raro, benigno, que se origina de una cavidad serosa. Aparece como masa mediastinal pediculada o polipoide que se adhiere a la pleura parietal o visceral. Comunicamos el caso de un hombre de 73 años de edad con un tumor mediastinal que ocupaba la mitad del hemitórax izquierdo. Se resecó el tumor, el cual tenía un peso de 3,900 g, medía 16 ï 15 cm, era blanco grisáceo, de aspecto fibroso y firme. Desde el punto de vista histológico, se caracterizaba por células fusiformes homogéneas con áreas de fibrosis y hialinización del estroma. Se discuten los hallazgos histopatológicos, radiológicos y clínicos.
