title: Clinical significance of BRAF mutation in thyroid papillary cancer.
abstract: OBJECTIVE
  To correlate the presence of BRAF V600E mutation with clinicopathological parameters.
  
  
  METHODS
  Case-control study.
  
  
  METHODS
  BRAF mutation represents the most common oncogenic event in sporadic papillary thyroid cancer (PTC). There are, however, significant discrepancies regarding the overall frequency and its relationship with clinicopathological parameters of poor outcome. We analyzed BRAF mutation in a cohort of patients affected by PTCs to identify its association with clinical variables.
  
  
  METHODS
  We analyzed retrospectively a series of 304 patients, treated for PTC from 1999 to 2011 at Bologna University Hospital. We searched BRAF mutation by reverse transcription polymerase chain reaction (PCR) followed by PCR and direct sequencing.
  
  
  RESULTS
  BRAF mutation was found in 77.4% of classical PTCs, 31.9% of the follicular variant, and 72.2% of high tall cell PTCs, being significantly associated, at univariate analysis, with recurrence, stage, multicentricity, histologic subtype, extrathyroidal extension, nodule dimension, body mass index, and American Thyroid Association (ATA) risk stratification. Furthermore, higher T, but not N or M, stage was associated with BRAF mutation. In the multivariate analysis, the BRAF mutation was significantly associated only with the ATA risk stratification, in turn showing a significant negative association with recurrence-free survival time with Cox multivariate analysis.
  
  
  CONCLUSIONS
  Our results indicate that BRAF mutation identifies a subset of PTC with increased risk of recurrence. The presence of BRAF mutation might be a valuable diagnostic and prognostic marker of the disease. To confirm the diagnostic usefulness of this marker, further studies should be carried out.
authors.affiliation: ENT Department, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy. ignafernandez@yahoo.it
authors.forename: Ignacio J
authors.initials: IJ
authors.lastname: Fernandez
authors.forename: Ottavio
authors.initials: O
authors.lastname: Piccin
authors.forename: Silvia
authors.initials: S
authors.lastname: Sciascia
authors.forename: Ottavio
authors.initials: O
authors.lastname: Cavicchi
authors.forename: Andrea
authors.initials: A
authors.lastname: Repaci
authors.forename: Valentina
authors.initials: V
authors.lastname: Vicennati
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Fiorentino
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D002277:Carcinoma / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D002291:Carcinoma, Papillary; D016022:Case-Control Studies; D002648:Child; D016001:Confidence Intervals; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation / Q000235:genetics*; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology*; D016133:Polymerase Chain Reaction / Q000379:methods; D016016:Proportional Hazards Models; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012189:Retrospective Studies; D018570:Risk Assessment; D018709:Statistics, Nonparametric; D015996:Survival Rate; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D004273:DNA, Neoplasm; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords:  BRAF mutation; papillary thyroid cancer; prognostic markers; thyroid cancer; thyroid surgery