BRAF mutation predicts a poorer clinical prognosis for papillary thyroid cancer.
BACKGROUND
Use of BRAF mutation in papillary thyroid cancer (PTC) has the potential to improve risk stratification of this cancer.


OBJECTIVE
The objective of the study was to investigate the prognostic value of BRAF mutation in patients with PTC.


METHODS
In a multicenter study of 219 PTC patients, data on their clinicopathological characteristics and clinical courses between 1990 and 2004 were retrospectively collected, and their tumor BRAF mutation status was determined. Associations of BRAF mutation with initial tumor characteristics and subsequent recurrence were analyzed.


METHODS
Relationships between the BRAF mutation status and clinicopathological outcomes, including recurrence, were measured.


RESULTS
We found a significant association between BRAF mutation and extrathyroidal invasion (P < 0.001), lymph node metastasis (P < 0.001), and advanced tumor stage III/IV (P = 0.007) at initial surgery. This association remained significant on multivariate analysis, adjusting for conventional clinicopathological predictors of recurrence excluding the histological PTC subtype, but was lost when the tumor subtype was included in the model. BRAF mutation was also significantly associated with tumor recurrence, 25 vs. 9% with and without mutation, respectively (P = 0.004), during a median of 15 (interquartile range, 3-29) months of follow-up. This association remained significant on multivariate analysis adjusting for conventional clinicopathological predictors of recurrence, even including the PTC subtype (odds ratio, 4.0; 95% confidence interval, 1.1-14.1; P = 0.03). BRAF mutation was even an independent predictor of recurrence in patients with stage I/II disease, 22 vs. 5% with and without BRAF mutation, respectively (P = 0.002). BRAF mutation was also more frequently associated with absence of tumor I-131 avidity and treatment failure of recurrent disease.


CONCLUSIONS
In patients with PTC, BRAF mutation is associated with poorer clinicopathological outcomes and independently predicts recurrence. Therefore, BRAF mutation may be a useful molecular marker to assist in risk stratification for patients with PTC.
Xing
Mingzhao
M
Division of Endocrinology and Metabolism, Johns Hopkins University School of Medicine, 1830 East Monument Street, Suite 333, Baltimore, Maryland 21287, USA. mxing1@jhmi.edu
Westra
William H
WH
Tufano
Ralph P
RP
Cohen
Yoram
Y
Rosenbaum
Eli
E
Rhoden
Kerry J
KJ
Carson
Kathryn A
KA
Vasko
Vasily
V
Larin
Alexandr
A
Tallini
Giovanni
G
Tolaney
Sara
S
Holt
Elizabeth H
EH
Hui
Pei
P
Umbricht
Christopher B
CB
Basaria
Shehzad
S
Ewertz
Marge
M
Tufaro
Anthony P
AP
Califano
Joseph A
JA
Ringel
Matthew D
MD
Zeiger
Martha A
MA
Sidransky
David
D
Ladenson
Paul W
PW
D000328:Adult; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology
C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf