Analise da expressão do gene BRAF e suas possiveis implicações diagnosticas e prognosticas para pacientes portadores de carcinoma papilifero da tireoide / BRAF expression may help identify malignant nodules and define outcomes in papillary thyroid cancer patients

AUTOR(ES)
FONTE

IBICT - Instituto Brasileiro de Informação em Ciência e Tecnologia

DATA DE PUBLICAÇÃO

31/08/2009

RESUMO

Background: Thyroid cancer is the most common endocrine malignancy, corresponding to 1% of all human neoplasms. Thyroid nodules are very frequent, mainly in women over 60 years. The relationship of BRAF gene with papillary thyroid tumorigenesis is well recognized in the literature. Its BRAFV600E mutation has been related to tumor aggressiveness and patients’ prognosis. Despite the role of BRAF gene expression as an important MAPK pathway promoter, its relationship to patients’ cancer suscetibility and clinical outcome is still poorly understood. The objective of this thesis was to measure mRNA BRAF expression in a determined population harboring thyroid nodules, in order to correlate these findings with prognosis at follow up, as well as to verify retrospectively the clinical importance of its ocurrence. Material/Methods: We determined the relative expression levels of wildtype BRAF and BRAFV600E mRNA obtained from fresh tissue samples collected by quantitative PCR (qRT-PCR) and cDNA—PCR-RFLP (restriction fragment length polymorphism) in a population of 166 thyroid nodule patients, in which 32 papillary thyroid cancer patients were selected for study as well as 35 patients harboring benign nodules, all submitted to total thyroidectomy and followed up to 56 months (21,3±12,45 months on average). Comparisons were made to well-recognized determinants in differentiated thyroid cancer. Results: Twenty-eight (87.5%) of 32 papillary thyroid carcinoma patients were female and one presented local recurrence at follow up (3,1%). BRAF hot spot mutation was identified in nine patients (28,1%). Of the 35 patients harboring benign nodules, seven (20%) comprehended follicular adenomas and 28 (80%) were multinodular goiters. Twenty-seven patients (77,1%) were female. These 35 patients had BRAF expression measured in order to perform a comparative study, in which BRAF expression distinguished benign and malignant nodules with a sensitivity of 80.6%, specificity of 77.1% and an accuracy of 78.8%. A 14-times increased risk for malignity was observed when BRAF expression was above the cut-off point of 4,712 arbitrary units (AU). There was not a significant correlation among BRAF expression (when mutation was excluded) and survival (r=0,54; p=0,007). Conclusion: We concluded that the quantification of BRAF expression may be useful for diagnosing malignant nodules. Nodules with BRAF expression higher than the cut-off point of 4,712 UA harbored a 14-times increased risk for malignity. There was not a significant correlation among BRAF expression and survival at this sample.

ASSUNTO(S)

tireoide tireoide - câncer predisposição genetica para doenças carcinoma papilar prognostico thyroid thyroid neoplasm genetic predisposition to disease carcinoma papillary prognosis

ACESSO AO ARTIGO

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