title: Higher rate of BRAF mutation in papillary thyroid cancer over time: a single-institution study.
abstract: BACKGROUND
  The incidence of thyroid cancer has doubled over the past decade. The reason for this dramatic increase in incidence is controversial. Some investigators have suggested that the increased incidence is because of increased detection of small primary tumors as a result of diagnostic scrutiny. Conversely, some investigators have demonstrated an increased incidence across all tumor sizes, suggesting that other factors may play a role. This study was undertaken to investigate the clinical, pathologic, and molecular changes present in papillary thyroid cancer over a 15-year period during which the incidence of papillary thyroid cancer doubled.
  
  
  METHODS
  A total of 628 patients with conventional papillary thyroid cancer and 228 tumor samples from a single institution were analyzed from 1991 to 2005. Time-trend analyses of demographic, clinical, pathologic, and tumor genotype were performed over three 5-year time periods: group I (1991-1995), group II (1996-2000), and group III (2001-2005).
  
  
  RESULTS
  The authors found no differences in age, sex, ethnicity, primary tumor size, rate of extrathyroidal invasion, or overall TNM cancer stage among the 3 time groups. The rate of BRAF V600E mutation was significantly higher in group III (88% BRAF V600E positive) as compared with groups I and II (51% and 43%, respectively) (P < .001). The rate of all the common somatic mutations was also significantly higher in group III (92% positive) as compared with groups I and II (68% and 64%, respectively) (P < .002).
  
  
  CONCLUSIONS
  The rate of BRAF V600E mutation increased significantly over a 15-year period at the authors' institution. The findings suggest that a higher rate of BRAF mutation in papillary thyroid cancer may contribute to the increasing incidence of thyroid cancer.
authors.affiliation: Endocrine Oncology Section, Surgery Branch, National Cancer Institute, Bethesda, Maryland, USA.
authors.forename: Aarti
authors.initials: A
authors.lastname: Mathur
authors.forename: Willeford
authors.initials: W
authors.lastname: Moses
authors.forename: Reza
authors.initials: R
authors.lastname: Rahbari
authors.forename: Elham
authors.initials: E
authors.lastname: Khanafshar
authors.forename: Quan-Yang
authors.initials: QY
authors.lastname: Duh
authors.forename: Orlo
authors.initials: O
authors.lastname: Clark
authors.forename: Electron
authors.initials: E
authors.lastname: Kebebew
mesh_terms: D000328:Adult; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000556:secondary / Q000601:surgery; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D015994:Incidence; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D015996:Survival Rate; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D013965:Thyroidectomy; D013997:Time Factors
chemical_list: D004273:DNA, Neoplasm; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf