title: Clinical significance of BRAF (V600E) mutation and Ki-67 labeling index in papillary thyroid carcinomas.
abstract: BACKGROUND
  Activating mutations of the BRAF gene have recently been reported in thyroid carcinomas. In particular, V600E mutation is highly prevalent in papillary thyroid carcinoma (PTC).
  
  
  METHODS
  In this study, the BRAF (V600E) mutation in 54 PTCs was investigated and the relationship between the BRAF mutation and clinicopathological features such as age, gender, tumor size, extrathyroid extension, lymph node metastasis, and distant metastasis was analyzed. Additionally, Ki-67 labeling index (LI) was determined to evaluate tumor cell proliferative activity.
  
  
  RESULTS
  The BRAF mutation was detected in 26 (65%) of 40 primary and 12 (85.7%) of 14 recurrent PTCs. The BRAF mutation was significantly related to older age (57.4 vs. 43.1 years, p=0.012), extrathyroid extension (76.9% vs. 35.7%, p=0.026), and lymph node metastasis (88.5% vs. 57.1%, p=0.044). Moreover, the mean Ki-67 LI was significantly higher in BRAF-positive patients than in BRAF-negative patients (1.01% vs. 0.135%, p=0.014). The BRAF mutation was common in PTCs classified as advanced TNM stage. Eighteen of 20 (90%) patients in TNM stages III and IV were positive for this gene mutation. Similarly, the BRAF mutation was investigated in 14 recurrent PTCs and was detected in 85.7% (12 of 14). The BRAF mutation was also common in patients with regional lymph node recurrence.
  
  
  CONCLUSIONS
  These results suggest that PTCs with BRAF (V600E) mutation are more aggressive than those with wildtype BRAF. This mutation may be important for predicting a worse prognosis in patients with PTC.
authors.affiliation: Department of General Surgery, Yokohama City University Hospital, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan. h-nak@kb3.so-net.ne.jp
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Nakayama
authors.forename: Akira
authors.initials: A
authors.lastname: Yoshida
authors.forename: Yoshiyasu
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hayashi
authors.forename: Youhei
authors.initials: Y
authors.lastname: Miyagi
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Wada
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Rino
authors.forename: Munetaka
authors.initials: M
authors.lastname: Masuda
authors.forename: Toshio
authors.initials: T
authors.lastname: Imada
mesh_terms: D001483:Base Sequence; D002291:Carcinoma, Papillary / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D018698:Glutamic Acid / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics*; D014633:Valine / Q000235:genetics*
chemical_list: D019394:Ki-67 Antigen; D018698:Glutamic Acid; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D014633:Valine