title: BRAF mutation predicts a poorer clinical prognosis for papillary thyroid cancer.
abstract: 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.
authors.affiliation: Division of Endocrinology and Metabolism, Johns Hopkins University School of Medicine, 1830 East Monument Street, Suite 333, Baltimore, Maryland 21287, USA. mxing1@jhmi.edu
authors.forename: Mingzhao
authors.initials: M
authors.lastname: Xing
authors.forename: William H
authors.initials: WH
authors.lastname: Westra
authors.forename: Ralph P
authors.initials: RP
authors.lastname: Tufano
authors.forename: Yoram
authors.initials: Y
authors.lastname: Cohen
authors.forename: Eli
authors.initials: E
authors.lastname: Rosenbaum
authors.forename: Kerry J
authors.initials: KJ
authors.lastname: Rhoden
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Carson
authors.forename: Vasily
authors.initials: V
authors.lastname: Vasko
authors.forename: Alexandr
authors.initials: A
authors.lastname: Larin
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tallini
authors.forename: Sara
authors.initials: S
authors.lastname: Tolaney
authors.forename: Elizabeth H
authors.initials: EH
authors.lastname: Holt
authors.forename: Pei
authors.initials: P
authors.lastname: Hui
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Umbricht
authors.forename: Shehzad
authors.initials: S
authors.lastname: Basaria
authors.forename: Marge
authors.initials: M
authors.lastname: Ewertz
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Tufaro
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Califano
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Ringel
authors.forename: Martha A
authors.initials: MA
authors.lastname: Zeiger
authors.forename: David
authors.initials: D
authors.lastname: Sidransky
authors.forename: Paul W
authors.initials: PW
authors.lastname: Ladenson
mesh_terms: 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
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf