title: BRAF mutation is not predictive of long-term outcome in papillary thyroid carcinoma.
abstract: The BRAF mutation occurs commonly in papillary thyroid carcinoma (PTC). Previous investigations of its utility to predict recurrence-free survival (RFS) and disease-specific survival (DSS) have reported conflicting results and its role remains unclear. The purpose of this retrospective study was to determine the incidence of the BRAF mutation and analyze its relationship to clinicopathologic risk factors and long-term outcomes in the largest, single-institution American cohort to date. BRAF mutational status was determined in 508 PTC patients using RFLP analysis. The relationships between BRAF mutation status, patient and tumor characteristics, RFS, and DSS were analyzed. The BRAF mutation was present in 67% of patients. On multivariate analysis, presence of the mutation predicted only for capsular invasion (HR, 1.7; 95% CI, 1.1-2.6), cervical lymph node involvement (HR, 1.7; 95% CI, 1.1-2.7), and classic papillary histology (HR, 1.8; 95% CI 1.1-2.9). There was no significant relationship between the BRAF mutation and RFS or DSS, an observation that was consistent across univariate, multivariate, and Kaplan-Meier analyses. This is the most extensive study to date in the United States to demonstrate that BRAF mutation is of no predictive value for recurrence or survival in PTC. We found correlations of BRAF status and several clinicopathologic characteristics of high-risk disease, but limited evidence that the mutation correlates with more extensive or aggressive disease. This analysis suggests that BRAF is minimally prognostic in PTC. However, prevalence of the BRAF mutation is 70% in the general population, providing the opportunity for targeted therapy.
authors.affiliation: Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Henke
authors.affiliation: Department of Pathology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: John D
authors.initials: JD
authors.lastname: Pfeifer
authors.affiliation: Department of Pathology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Changquing
authors.initials: C
authors.lastname: Ma
authors.affiliation: Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Perkins
authors.affiliation: Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Todd
authors.initials: T
authors.lastname: DeWees
authors.affiliation: Department of Pathology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Samir
authors.initials: S
authors.lastname: El-Mofty
authors.affiliation: Section of Endocrine and Oncologic Surgery, Department of General Surgery, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Jeffrey F
authors.initials: JF
authors.lastname: Moley
authors.affiliation: Department of Otolaryngology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Brian
authors.initials: B
authors.lastname: Nussenbaum
authors.affiliation: Department of Otolaryngology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Bruce H
authors.initials: BH
authors.lastname: Haughey
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Washington University School of Medicine, Saint Louis, Missouri.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Baranski
authors.affiliation: Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Julie K
authors.initials: JK
authors.lastname: Schwarz
authors.affiliation: Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri.|Division of Nuclear Medicine, Mallinckrodt Institute of Radiology, Washington University School of Medicine, Saint Louis, Missouri.
authors.forename: Perry W
authors.initials: PW
authors.lastname: Grigsby
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D002291:Carcinoma, Papillary; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000401:mortality; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D014481:United States / Q000453:epidemiology; D055815:Young Adult
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF V600; BRAF mutation; BRAF mutation survival; papillary thyroid carcinoma; thyroidectomy