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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
Bastos, Andre Uchimura [1] ; Oler, Gisele [1] ; Nakano Nozima, Bruno Heidi [1] ; Moyses, Raquel Ajub [2] ; Cerutti, Janete Maria [1]
Total Authors: 5
Affiliation:
[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
Total Affiliations: 2
Document type: Journal article
Source: EUROPEAN JOURNAL OF ENDOCRINOLOGY; v. 173, n. 4, p. 525-540, OCT 2015.
Web of Science Citations: 24
Abstract

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)

FAPESP's process: 11/10787-2 - Papilary Thyroid Carcinoma: Identification od RET/PTC rearrangement and BRAF, RAS and PIK3CA mutations and correlation with clinical-pathological features and modulation of gene expression
Grantee:Janete Maria Cerutti
Support type: Regular Research Grants
FAPESP's process: 12/02902-9 - The role of microRNAs in the regulation of C1orf24 expression in thyroid tumors
Grantee:Janete Maria Cerutti
Support type: Regular Research Grants
FAPESP's process: 13/03867-5 - Analysis of copy number variation (CNV) in pacientes of a family with men 2A and P.G533C mutation in the RET gene: identification of CNV regions associated with genesis and progression of medullary thyroid carcinoma
Grantee:Janete Maria Cerutti
Support type: Regular Research Grants