title: Lack of association of BRAF mutation with negative prognostic indicators in papillary thyroid carcinoma: the University of California, San Francisco, experience.
abstract: OBJECTIVE
  Papillary thyroid carcinoma (PTC) is the most common endocrine neoplasm. B-type raf kinase (BRAF) V600E mutation has been proposed as a negative prognostic indicator in PTC, and patients harboring it should receive more aggressive initial therapy.
  
  
  OBJECTIVE
  To assess the significance of BRAF V600E mutation in PTC in the largest US sample to date.
  
  
  METHODS
  We identified patients from our institution's pathology archives diagnosed as having PTC and meeting criteria for BRAF mutation testing. Medical records were analyzed for BRAF status (positive or negative) and a list of standardized clinicopathologic features.
  
  
  METHODS
  A total of 429 patients with PTC at an academic medical center.
  
  
  METHODS
  Clinicopathologic features in patients with PTC with and without BRAF mutation.
  
  
  RESULTS
  Of 429 cases with PTC, 314 (73.2%) were positive for the BRAF mutation and 115 (26.8%) tested negative. BRAF mutation was significantly associated with tumor margin positivity (P = .03) and lymph node metastasis (P = .002) on univariate analysis but not on multivariate study. BRAF mutation was a predictor of male sex (odds ratio [OR], 3.2; 95% CI, 1.4-7.2), total thyroidectomy (OR, 2.6; 95% CI, 1.1-6.2), and a negative predictor of follicular variant PTC (OR, 0.1; 95% CI, 0.1-0.4). There was no significant association between BRAF positivity and tumor multicentricity, lymphovascular invasion, extranodal extension, central neck involvement, advanced stage (stage III or IV), and distant metastasis.
  
  
  CONCLUSIONS
  BRAF V600E mutation has been extensively studied in relation to negative prognostic indicators in PTC, with no consistent relationship emerging. Two recent meta-analyses showed an overall association between BRAF status and aggressive disease features and called for tailoring treatment plans in patients accordingly. In this, the largest US study to date, BRAF status was not significantly associated with most clinicopathologic features suggestive of more aggressive disease.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of California, San Francisco, San Francisco2Department of Otolaryngology-Head and Neck Surgery, Northwestern University, Chicago, Illinois.
authors.forename: Christopher
authors.initials: C
authors.lastname: Gouveia
authors.forename: Nhu Thuy
authors.initials: NT
authors.lastname: Can
authors.forename: Alan
authors.initials: A
authors.lastname: Bostrom
authors.forename: James P
authors.initials: JP
authors.lastname: Grenert
authors.forename: Annemieke
authors.initials: A
authors.lastname: van Zante
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Orloff
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002291:Carcinoma, Papillary; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D006785:Hospitals, University; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics* / Q000378:metabolism; D012495:San Francisco; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf