The role of BRAF(V600E) mutation as poor prognostic factor for the outcome of patients with intrathyroid papillary thyroid carcinoma.
BACKGROUND
BRAF(V600E) mutation, which represents the most frequent genetic mutation in papillary thyroid carcinoma (PTC), is widely considered to have an adverse outcome on PTC outcome, however its real predictive value is not still well stated. The aim of the present study was to evaluate if BRAF(V600E) mutation could be useful to identify within patients with intrathyroid ultrasound-N0 PTC those who require more aggressive treatment, by central neck node dissection (CLND) or subsequent postoperative (131)I treatment.


METHODS
Among the whole series of 931 consecutive PTC patients operated on at 2nd Clinical Surgery of University of Padova and at General Surgery Department of University of Trieste during a period from January 2007 to December 2012, we selected 226 patients with an intrathyroid tumor and no metastases (preoperative staging T1-T2, N0, M0). BRAF(V600E) mutation was evaluated by PCR-single-strand conformation polymorphism analysis and direct genomic sequencing. We analyzed the correlation between the presence/absence of the BRAF(V600E) mutation in the fine-needle aspiration (FNA) and the clinical-pathological features: age, gender, extension of surgery, node dissection, rate of cervical lymph node involvement, tumor size, TNM stage, variant of histotype, mono/plurifocality, association with lymphocitary chronic thyroiditis, radioactive iodine ablation doses, and outcome.


RESULTS
The BRAF(V600E) mutation was present in 104 of 226 PTC patients (47.8%). BRAF(V600E) mutation correlated with multifocality, more aggressive variants, infiltration of the tumoral capsule, and greater tumor's diameter. BRAF(V600E) mutation was the only poor prognostic factor in these patients.


CONCLUSIONS
In our series, BRAF(V600E) mutation demonstrated to be an adverse prognostic factor indicating aggressiveness of disease and it could be useful in the management of low-risk PTC patients, as supplementary prognostic factor to assess the preoperative risk stratification with the aim to avoid unnecessary central neck node dissection (BRAF pos.) or to perform complementary (131)I-therapy (BFAF neg.).
Surgical Clinic II, Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, Padova, Italy.
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MR
Pelizzo
Division of General Surgery, Department of Medical and Surgical Sciences, Hospital of Cattinara, University of Trieste, Trieste, Italy.
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C
Dobrinja
Surgical Clinic II, Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, Padova, Italy.
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Casal Ide
Surgical Clinic II, Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, Padova, Italy.
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M
Zane
Radiotherapy and Nuclear Medicine Unit, Istituto Oncologico Veneto-IRCCS, Padova, Italy.
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O
Lora
Surgical Clinic II, Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, Padova, Italy.
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A
Toniato
Endocrinology Unit, Department of Medicine, University of Padova, Padova, Italy.
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C
Mian
Endocrinology Unit, Department of Medicine, University of Padova, Padova, Italy.
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S
Barollo
Surgical Clinic II, Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, Padova, Italy.
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M
Izuzquiza
Division of General Surgery, Department of Medical and Surgical Sciences, Hospital of Cattinara, University of Trieste, Trieste, Italy.
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J
Guerrini
Division of General Surgery, Department of Medical and Surgical Sciences, Hospital of Cattinara, University of Trieste, Trieste, Italy.
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N
De Manzini
Surgical Clinic II, Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, Padova, Italy.
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I
Merante Boschin
Department of Imaging, Nuclear Medicine, PET/CT Centre, Radiology, Neuroradiology, Medical Physics, Santa Maria della Misericordia Hospital, Rovigo, Italy. Electronic address: domenico.rubello@libero.it.
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Rubello
D000293:Adolescent; D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000235:genetics / Q000473:pathology*; D002291:Carcinoma, Papillary; D002648:Child; D005260:Female; D023281:Genomics; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics / Q000473:pathology*; D055815:Young Adult
C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
BRAF mutation; Papillary thyroid carcinoma; Thyroid cancer