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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

BRAF V600E and decreased NIS and TPO expression are associated with aggressiveness of a subgroup of papillary thyroid microcarcinoma

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Autor(es):
Bastos, Andre Uchimura [1] ; Oler, Gisele [1] ; Nakano Nozima, Bruno Heidi [1] ; Moyses, Raquel Ajub [2] ; Cerutti, Janete Maria [1]
Número total de Autores: 5
Afiliação do(s) autor(es):
[1] Univ Fed Sao Paulo UNIFESP, Dept Morfol & Genet, Disciplina Genet, Lab Bases Genet Tumores Tiroide, BR-04039032 Sao Paulo - Brazil
[2] Univ Sao Paulo, Dept Cirurgia, Disciplina Cirurgia Cabeca & Pescoc, Sao Paulo - Brazil
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Fonte: EUROPEAN JOURNAL OF ENDOCRINOLOGY; v. 173, n. 4, p. 525-540, OCT 2015.
Citações Web of Science: 24
Resumo

Background: Thyroid cancer incidence has dramatically increased worldwide over the last two decades. The rise is mostly due to an increased detection of small papillary thyroid carcinomas (PTCs) (<= 20 mm), predominantly microPTC (<= 10 mm). Although small tumors generally have an excellent outcome, a considerable percentage may have a more aggressive disease and worse prognosis. The clinical challenge is to preoperatively identify those tumors that are more likely to recur. Aim: To improve risk stratification and patient management, we sought to determine the prognostic value of BRAF V600E, NRAS or RET/PTC mutations in patients with PTC measuring < 20 mm, mainly microPTC. Methods: The prevalence of RET/PTC fusion genes was examined by quantitative RT-PCR. BRAF V600E and NRAS Q61 mutations were determined by PCR sequencing. To further elucidate why some small PTC are less responsive to radioactive iodine treatment therapy, we explored if these genetic alterations may modulate the expression of iodine metabolism genes (NIS, TPO, TG, TSHR and PDS) and correlated with clinico-pathological findings that are predictors of recurrence. Results: This study shows that tumors measuring <= 20 mm exhibited higher prevalence of BRAF V600E mutation, which correlated with aggressive histopathological parameters, higher risk of recurrence, and lower expression of NIS and TPO. Although this correlation was not found when microPTC were evaluated, we show that tumors measuring 7-10 mm, which were positive for BRAF mutation, presented more aggressive features and lower expression of NIS and TPO. Conclusion: We believe that our findings will help to decide the realistic usefulness of BRAF V600E mutation as a preoperative marker of poor prognosis in small PTC, primarily in microPTC. (AU)

Processo FAPESP: 11/10787-2 - Carcinoma papilífero da tiróide: identificação de rearranjos RET/PTC, mutações nos genes BRAF, RAS e PIK3CA e correlação com características clínico-patológicas e modulação da expressão gênica
Beneficiário:Janete Maria Cerutti
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 12/02902-9 - Investigação do papel dos microRNAs na regulação da expressão do gene C1orf24 em tumores da tiróide humana
Beneficiário:Janete Maria Cerutti
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 13/03867-5 - Análise da variação no número de cópias (CNV) de segmentos de DNA em pacientes de uma família com síndrome nem 2ª e mutação p.G533C no gene RET: identificação de regiões associadas à gênese e progressão do carcinoma medular da tiróide
Beneficiário:Janete Maria Cerutti
Linha de fomento: Auxílio à Pesquisa - Regular