Pre-operative role of BRAF in the guidance of the surgical approach and prognosis of differentiated thyroid carcinoma

Autor(es)

Danilovic, Debora L. S. ^{[1, 2]} ; Lima, Erika U. ^[1] ; Domingues, Regina B. ^[3] ; Brandao, Lenine G. ^[4] ; Hoff, Ana O. ^[2] ; Marui, Suemi ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med, Unidade Tireoide, Lab Endocrinol Celular & Mol LIM25, BR-01246903 Sao Paulo - Brazil

^[2] Inst Canc Estado Sao Paulo, Serv Endocrinol, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Fac Med, Hosp Clin, Serv Anat Patol, BR-01246903 Sao Paulo - Brazil

^[4] Univ Sao Paulo, Fac Med, Hosp Clin, Serv Cirurgia Cabeca & Pescoco, BR-01246903 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: EUROPEAN JOURNAL OF ENDOCRINOLOGY; v. 170, n. 4, p. 619-625, APR 2014.
• Citações Web of Science: 16

Resumo

Objective: The p. V600E BRAF and RAS mutations are found in 30-80% of differentiated thyroid carcinoma (DTC). BRAF mutation has been associated with poor prognosis. This study investigated the role of molecular studies in preoperative diagnosis of DTC and the association of p. V600E mutation with prognostic factors. Design: Prospective study. Methods: A total of 202 patients with cytological diagnosis of Bethesda III-VI underwent preoperative molecular studies and subsequent thyroidectomy. p. V600E and RAS mutations were studied in the cytology smears, using real-time PCR genotyping technique. The BRAF mutation (BRAF(+) or BRAF(-)) was correlated with histological and clinical findings. Results: Molecular study of 172 nodules with Bethesda III-V cytology improved negative predictive value and accuracy of Bethesda III and IV diagnosis. BRAF mutation was present in 65% of 94 DTC and p. Q61R NRAS in one. Except for age, BRAF C and BRAF(1) did not differ in sex, tumor size, histological subtype, multifocality, vascular invasion, extrathyroidal extension, or prognostic staging. Among papillary carcinomas, lymph node (LN) metastasis was diagnosed in 23% BRAF C and 37% BRAF K. Distant metastasis occurred in four BRAF(-) . Recurrent or persistent disease was more frequent in BRAF K (26.7 vs 3.3% BRAF(+), P=0.002) along follow-up of 29.8 +/- 10 months. BRAF(+) patients without LN metastasis by pre-operative evaluation submitted to thyroidectomy with central neck dissection ( CND) had more frequent LN metastasis ( 45 vs 5% no CND, P=0.002), but no difference in clinical outcome was observed. Conclusions: Pre-operative identification of BRAF mutation improved cytological diagnosis of DTC, but it was not associated with poor prognostic factors. Prophylactic CND did not guarantee better outcome in BRAF C patients. (AU)

• Processo FAPESP: 10/12883-6 - Detecção de mutações nos gene RAS em células foliculares de nódulo tireoidiano obtidas por punção aspirativa com agulha fina
• Beneficiário: Suemi Marui
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 09/07544-0 - Análise da mutação V600E do gene BRAF em punção aspirativa com agulha fina (PAAF) de nódulo tireoidiano com diagnóstico suspeito ou de carcinoma papilífero
• Beneficiário: Suemi Marui
• Modalidade de apoio: Auxílio à Pesquisa - Regular