Investigação de ocorrência de alterações moleculares nos genes KRAS, HRAS, NRAS e BRAF em carcinoma papilífero da tireóide

Abstract

The most common cancer of the thyroid is the papillary carcinoma (PTC), which represents 80% of the cases of cancer affecting this gland. PTC is a malignant tumor, with slow evolution, found in any age, but with a higher occurrence in patients between 30-40 years old. The metabolic pathway MAPK is the most associated with PTC. Among the several proteins which have a role in this pathway, we highlight the ones encoded by the genes belonging to families RAS and BRAF. Considering that there are few clinical and genetic studies focusing on thyroid cancer from Brazilian Amazonian region, the aim of this study was to investigate the occurrence of alterations in genes HRAS, NRAS, KRAS and BRAF in patients with PTC treated in a public hospitals, from Belém (PA), seeking to make an association between the mutations found and the biochemical and clinical findings. To achieve this goal, polymerase chain reaction (PCR) and direct automatic sequencing were used. Statistical analyses were performed using the software SPSS version 21.0. Continuous data were expressed as means and standard deviation and categorical data were described in terms of percentages. Student t Test was used to evaluate the continuous variables, while Fisher exact test and Chi-square were used to analyze categorical variables. We considered p<0.05 as significant value in all the analyses. Our results showed that, among the analyzed genes, only BRAF showed a mutation, BRAFV600E, in 21 out of the 53 patients (16 female and 5 males, 39.6%). Additionally, a new mutation in codon 38 of gene K-RAS was found (p.D38E). Considering clinical data, we found a significant association between the BRAFV600E mutation and hoarseness, as well as between this mutation and lymph node metastasis. In addition, the observation of a new mutation in the K-RAS gene indicates that the number of gene changes involving the MAPK pathway is still incomplete. The data obtained can be used for a better pre-surgical evaluation of thyroid tumors, in order to increase the sensitivity for the detection of cancer and avoid unnecessary surgeries of lesions erroneously identified as malignant.