BRAF(V600E) mutation and outcome of patients with papillary thyroid carcinoma: a 15-year median follow-up study.
BACKGROUND
The BRAF(V600E) mutation is the most frequent genetic alteration in papillary thyroid carcinoma (PTC). The role of BRAF(V600E) mutation as a poor prognostic factor has been controversially reported in series with short-term follow-ups. In this study we verified the prognostic value of the BRAF(V600E) mutation in PTC patients with a long-term follow-up.


METHODS
We studied 102 PTC patients with a median follow-up of 15 yr. The BRAF(V600E) mutation was analyzed by PCR-single-strand conformational polymorphism and sequencing. The correlation between the presence/absence of the BRAF(V600E) mutation, clinicopathological features, and outcome of PTC patients were evaluated.


RESULTS
The BRAF(V600E) mutation was found in 38 of 102 (37.3%) PTC patients, and was significantly more frequent in patients older than 60 yr (P = 0.02), in advanced stages (P = 0.03), and in cases with vascular invasion (P = 0.02). At univariate analysis the worst outcome for PTC patients was significantly correlated with clinicopathological features (i.e. age, tumor size, extrathyroid extension, lymph node and distant metastases, advanced stage, vascular endothelial growth factor expression, and vascular invasion) and the BRAF(V600E) mutation (P < 0.002). However, at multivariate analysis only the BRAF(V600E) mutation showed an independent correlation with the worst outcome (P = 0.03). Moreover, the survival curves of PTC patients showed a lower percentage of survivors in the BRAF(V600E)-mutated group (P = 0.015).


CONCLUSIONS
In this study the BRAF(V600E) mutation correlated with the worst outcome for PTC patients, who were not only at a higher risk not to be cured but also for death. In particular, the BRAF(V600E) mutation was demonstrated to be a poor prognostic factor independent from other clinicopathological features.
Elisei
Rossella
R
Department of Endocrinology, University of Pisa, Via Paradisa 2, 56124 Pisa, Italy. relisei@endoc.med.unipi.it
Ugolini
Clara
C
Viola
David
D
Lupi
Cristiana
C
Biagini
Agnese
A
Giannini
Riccardo
R
Romei
Cristina
C
Miccoli
Paolo
P
Pinchera
Aldo
A
Basolo
Fulvio
F
D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D002291:Carcinoma, Papillary / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D002648:Child; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016019:Survival Analysis; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000473:pathology
D014408:Biomarkers, Tumor; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf