The BRAF(V600E) mutation influences the short- and medium-term outcomes of classic papillary thyroid cancer, but is not an independent predictor of unfavorable outcome.
BACKGROUND
The prognostic usefulness of BRAF(V600E) evaluation in papillary thyroid cancer (PTC) has been analyzed in many studies, with controversial conclusions.


OBJECTIVE
To analyze the clinical relevance of BRAF(V600E) measurement in a homogenous series of PTC patients followed in a single institution.


METHODS
One hundred three classical variant PTC patients who underwent total thyroidectomy in the 3-year period between 2005 and 2008 were retrospectively selected, and BRAF(V600E) assessment was performed using paraffin-embedded archival specimens in 2013. All patients were actively followed at our medical center, with an average follow-up of 55±13 months.


RESULTS
BRAF(V600E) mutation-positive cancers (55.3%) were more frequently associated with lymph node metastasis (p=0.01) and advanced TNM stage (III-IV) (p=0.03). These findings were also confirmed in the subset of 42 microcarcinomas. BRAF(V600E)-positive patients were also at a higher risk of persistent disease (OR 3.5 [95% confidence interval {CI} 1.2-10.3], p=0.03) in univariate but not multivariate analysis (OR 2.8 [CI 0.7-11.8], p=0.2). Lymph node involvement was an independent predictor of persistent disease (OR 30.9 [CI 6.0-159.0], p<0.0001). Kaplan-Meier curves confirmed a higher percentage of persistent/recurrent disease in BRAF(V600E)-positive patients (p=0.02). However, the BRAF(V600E) mutation did not change the recurrence rate of PTC in subgroup analyses on the basis of other established risk factors (p=0.2).


CONCLUSIONS
BRAF(V600E)-positive tumors were at higher risk of developing more aggressive behavior and were associated with less favorable outcomes in the short and medium term, but the BRAF(V600E) mutation was not an independent predictor of unfavorable outcome. Therefore, its use as a prognostic marker in clinical practice is not advisable.
1 Endocrinology, Department of Clinical and Molecular Biomedicine, University of Catania , Catania, Italy .
Marco
M
Russo
Pasqualino
P
Malandrino
Maria Luisa
ML
Nicolosi
Mario
M
Manusia
Ilenia
I
Marturano
Maria Antonietta
MA
Trovato
Gabriella
G
Pellegriti
Francesco
F
Frasca
Riccardo
R
Vigneri
D000328:Adult; D002277:Carcinoma / Q000235:genetics* / Q000401:mortality; D002291:Carcinoma, Papillary; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D009364:Neoplasm Recurrence, Local; D016133:Polymerase Chain Reaction; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012189:Retrospective Studies; D013954:Thyroglobulin / Q000097:blood; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000401:mortality; D013965:Thyroidectomy; D016896:Treatment Outcome
D013954:Thyroglobulin; D048493:Proto-Oncogene Proteins B-raf