title: The prevalence and prognostic value of BRAF mutation in thyroid cancer.
abstract: OBJECTIVE
  To examine the prevalence of BRAF mutation among thyroid cancer histologic subtypes and determine the association of BRAF mutation with indicators of poor prognosis for papillary thyroid cancer and patient outcome.
  
  
  BACKGROUND
  The appropriate extent of surgical treatment, adjuvant therapy and follow-up monitoring for thyroid cancer remains controversial. Advances in the molecular biology of thyroid cancer have helped to identify candidate markers of disease aggressiveness. A commonly found genetic alternation is a point mutation in the BRAF oncogene (BRAF V600E), which is primarily found in papillary thyroid cancer and is associated with more aggressive disease.
  
  
  METHODS
  BRAF V600E mutation status was determined in 347 tumor samples from 314 patients with thyroid cancer (245 with conventional papillary thyroid cancer, 73 with follicular thyroid cancer, and 29 with the follicular variant of papillary thyroid cancer). Univariate and multivariate analyses were performed to determine the association of BRAF V600E with clinicopathologic factors and patient outcome.
  
  
  RESULTS
  : The prevalence of BRAF V600E mutation was higher in conventional papillary thyroid cancer (51.0%) than in follicular variant of papillary thyroid cancer (24.1%) and follicular thyroid cancer (1.4%) (P < 0.0001). In patients with conventional papillary thyroid cancer, BRAF V600E mutation was associated with older age (P = 0.0381), lymph node metastasis (P = 0.0323), distant metastasis (P = 0.045), higher TNM stage (I and II vs. III and IV, P = 0.0389), and recurrent and persistent disease (P = 0.009) with a median follow-up time of 6.0 years. Multivariate analysis showed that BRAF V600E mutation [OR (95% CI) = 4.2 (1.2-14.6)] and lymph node metastasis [OR (95% CI) = 7.75 (2.1-28.5)] were independently associated with recurrent and persistent disease in patients with conventional papillary thyroid cancer.
  
  
  CONCLUSIONS
  BRAF V600E mutation is primarily present in conventional papillary thyroid cancer. It is associated with an aggressive tumor phenotype and higher risk of recurrent and persistent disease in patients with conventional papillary thyroid cancer. Testing for this mutation may be useful for selecting initial therapy and for follow-up monitoring.
authors: Department of Surgery, University of California, San Francisco, San Francisco, California 94143-1674, USA. kebebewe@surgery.ucsf.edu
authors: Electron
authors: E
authors: Kebebew
authors: Julie
authors: J
authors: Weng
authors: Juergen
authors: J
authors: Bauer
authors: Gustavo
authors: G
authors: Ranvier
authors: Orlo H
authors: OH
authors: Clark
authors: Quan-Yang
authors: QY
authors: Duh
authors: Daniel
authors: D
authors: Shibru
authors: Boris
authors: B
authors: Bastian
authors: Ann
authors: A
authors: Griffin
mesh_terms: D002291:Carcinoma, Papillary / Q000235:genetics*; D018265:Carcinoma, Papillary, Follicular / Q000235:genetics; D016009:Chi-Square Distribution; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D015995:Prevalence; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D018709:Statistics, Nonparametric; D013964:Thyroid Neoplasms / Q000235:genetics*
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
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