title: The prognostic significance of the BRAF V600E mutation in papillary thyroid carcinoma detected by mutation-specific immunohistochemistry.
abstract: BRAF mutation has been shown in a large meta-analysis to be an independent prognostic marker for papillary thyroid carcinoma (PTC) with poorer survival and higher recurrence rates.
  
  
  
  We studied prevalence of BRAF mutation in 77 patients with PTC from an Australian cohort using competitive polymerase chain reaction (C-PCR) and immunohistochemistry (IHC) with BRAF-specific antibody, VE1. Clinicopathological parameters, recurrence and mortality were analysed according to BRAF mutation status.
  
  
  
  Median follow-up was 84.5 months. BRAF mutation was demonstrated in 65% of cases combining both C-PCR and IHC; in 71% (37/77) of tumours >1 cm and 52% (13/25) of microcarcinomas (<1 cm). IHC was positive in 69% (49/71) and C-PCR in 53% (41/77); 87% (67/77) of our patients were treated with total thyroidectomy and 65% (50/77) also had radioactive ablation. BRAF positive tumours had a significantly higher rate of subsequent lymph node metastases (p=0.035). Significant association was found between BRAF mutation and male sex (p=0.034), but not between age >45 years at diagnosis, size of primary tumour, extrathyroidal extension, lymph node or distant metastases or clinical stage at diagnosis.
  
  
  
  BRAF mutation in PTC determined by IHC is associated with significantly increased risk of lymph node recurrence.
authors.affiliation: *Departments of Anatomical Pathology †Surgery, St Vincent's Hospital, Melbourne ‡Department of Pathology, University of Melbourne, Melbourne, Victoria, Australia; ‡these authors contributed equally.
authors.forename: Penelope A
authors.initials: PA
authors.lastname: McKelvie
authors.forename: Fiona
authors.initials: F
authors.lastname: Chan
authors.forename: Yong
authors.initials: Y
authors.lastname: Yu
authors.forename: Paul
authors.initials: P
authors.lastname: Waring
authors.forename: Irma
authors.initials: I
authors.lastname: Gresshoff
authors.forename: Stephen
authors.initials: S
authors.lastname: Farrell
authors.forename: Richard A
authors.initials: RA
authors.lastname: Williams
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics* / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D048493:Proto-Oncogene Proteins B-raf