title: BRAF V600E mutation independently predicts central compartment lymph node metastasis in patients with papillary thyroid cancer.
abstract: OBJECTIVE
  This study was designed to examine whether available preoperative clinical parameters, including B-type Raf kinase (BRAF) V600E mutation status, can identify patients at risk for central compartment lymph node metastasis (CLNM).
  
  
  METHODS
  Under an institutional review board-approved protocol, we conducted a single-center, retrospective review of all patients who had initial thyroidectomy for histologic papillary thyroid carcinoma (PTC) during 2010. The presence of CLNM was examined for correlation with available preoperative clinical parameters, including tumor size, gender, age, and BRAF mutation status.
  
  
  RESULTS
  Cervical lymph node resection and molecular testing on FNAB or histopathologic specimen was performed on a consecutive series of 156 study patients with histologic PTC. Overall, CLNM was diagnosed in 37% and 46% were BRAF-mutation-positive. BRAF positivity was the only clinical parameter associated with CLNM (BRAF, p=0.002; tumor size≥2 cm, p=0.16; male gender, p=0.1; age≥45 years, p=0.3) and remained an independent predictor of CLNM on multiple logistic regression analysis (odds ratio (OR) 3.2, p=0.001). The PPV and NPV of BRAF positivity for CLNM was 50 and 74%, respectively. When restricting the analysis to the subset of 38 patients who had molecular testing performed preoperatively on FNAB, the PPV and NPV of BRAF positivity for CLNM was 47 and 91%, respectively, and BRAF positivity was still a significant predictor of CLNM on both univariate (OR 8.4, p=0.01) and multivariate (OR 9.7, p=0.02) analyses.
  
  
  CONCLUSIONS
  Of the commonly used clinical parameters available preoperatively, the BRAF V600E mutation is the only independent predictor of CLNM in PTC and can be utilized to guide the extent of initial surgery.
authors.affiliation: Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Gina M
authors.initials: GM
authors.lastname: Howell
authors.forename: Marina N
authors.initials: MN
authors.lastname: Nikiforova
authors.forename: Sally E
authors.initials: SE
authors.lastname: Carty
authors.forename: Michaele J
authors.initials: MJ
authors.lastname: Armstrong
authors.forename: Steven P
authors.initials: SP
authors.lastname: Hodak
authors.forename: Michael T
authors.initials: MT
authors.lastname: Stang
authors.forename: Kelly L
authors.initials: KL
authors.lastname: McCoy
authors.forename: Yuri E
authors.initials: YE
authors.lastname: Nikiforov
authors.forename: Linwah
authors.initials: L
authors.lastname: Yip
mesh_terms: D000328:Adult; D044963:Biopsy, Fine-Needle; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000556:secondary* / Q000601:surgery; D005260:Female; D006801:Humans; D016015:Logistic Models; D008198:Lymph Nodes / Q000473:pathology* / Q000601:surgery; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D037981:Neck Dissection; D016017:Odds Ratio; D011237:Predictive Value of Tests; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012189:Retrospective Studies; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000601:surgery
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf