title: Circulating BRAFV600E in the diagnosis and follow-up of differentiated papillary thyroid carcinoma.
abstract: BACKGROUND
  Cell-free nucleic acids circulating in plasma are considered a promising noninvasive tool for cancer monitoring. BRAF(V600E) mutation in cell-free DNA (cfDNA) could represent an appropriate marker for papillary thyroid carcinoma (PTC).
  
  
  OBJECTIVE
  Our aim is to investigate the role of BRAF(V600E)-mutated allele in cfDNA as a marker for the diagnosis and follow-up of PTC.
  
  
  METHODS
  BRAF(V600E) allele was detected and quantified by an allele-specific real-time quantitative PCR assay in plasma from 103 patients affected by nodular goiter. As control populations, we enrolled 49 healthy subjects and 16 patients with non-nodular thyroid diseases.
  
  
  RESULTS
  The percentage of circulating BRAF(V600E) was significantly different between patients and controls and throughout different cytological categories of ultrasound-assisted fine-needle aspiration. Patients with a histopathological diagnosis of PTC showed a higher percentage of circulating BRAF(V600E) (P = .035) compared to those with benign histology. In 19 patients, a second blood draw, taken 3-6 months after surgery, showed a lower percentage of BRAF(V600E) in cfDNA than the presurgical sample (P < .001). The diagnostic performance of circulating BRAF(V600E) was assessed by receiver operating characteristic curve analysis resulting in an area under the curve of 0.797. A cutoff value was chosen corresponding to maximum specificity (65%) and sensitivity (80%). On this basis, we evaluated the predictive value of BRAF(V600E) in Thy 3 patients with a resulting positive predictive value of 33% and a negative predictive value of 80%.
  
  
  CONCLUSIONS
  The results of the present study provide encouraging data supporting the possibility to take advantage of circulating BRAF(V600E) in the management of PTC.
authors.affiliation: Endocrinology Unit, Careggi University Hospital, 50141 Florence, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Pupilli
authors.forename: P
authors.initials: P
authors.lastname: Pinzani
authors.forename: F
authors.initials: F
authors.lastname: Salvianti
authors.forename: B
authors.initials: B
authors.lastname: Fibbi
authors.forename: M
authors.initials: M
authors.lastname: Rossi
authors.forename: L
authors.initials: L
authors.lastname: Petrone
authors.forename: G
authors.initials: G
authors.lastname: Perigli
authors.forename: M L
authors.initials: ML
authors.lastname: De Feo
authors.forename: V
authors.initials: V
authors.lastname: Vezzosi
authors.forename: M
authors.initials: M
authors.lastname: Pazzagli
authors.forename: C
authors.initials: C
authors.lastname: Orlando
authors.forename: G
authors.initials: G
authors.lastname: Forti
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D002291:Carcinoma, Papillary; D004247:DNA / Q000032:analysis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000097:blood / Q000235:genetics*; D012372:ROC Curve; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology
chemical_list: D004247:DNA; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf