title: Papillary thyroid carcinomas with and without BRAF V600E mutations are morphologically distinct.
abstract: OBJECTIVE
  The BRAF V600E mutation resulting in the production of an abnormal BRAF protein has emerged as the most frequent genetic alteration in papillary thyroid carcinomas (PTCs). This study was aimed at identifying distinctive features in tumours with and without the mutation.
  
  
  RESULTS
  Thirty-four mutation-positive and 22 mutation-negative tumours were identified by single-strand conformation polymorphism of the amplified BRAF V600E region in the tumour DNA. Mutation-positive tumours were more common in patients older than 45 years (24/33, P = 0.05), in classic (23/30, P = 0.01), tall cell (4/5) and oncocytic/Warthin-like (2/2) variants of PTC, and in subcapsular sclerosing microcarcinomas (4/4). In contrast, all 12 follicular variants (P < 0.0001) and two diffuse sclerosing variants were negative for the mutation. Mutation-positive tumours displayed infiltrative growth (32/34, P = 0.02), stromal fibrosis (33/34, P < 0.001), psammoma bodies (17/34, P = 0.05), plump eosinophilic tumour cells (22/34, P = 0.01), and classic fully developed nuclear features of PTC (33/34, P = 0.0001). Encapsulation was significantly associated with mutation-negative tumours (15/22, P = 0.02).
  
  
  CONCLUSIONS
  BRAF V600E mutation-positive and negative PTCs are morphologically different. Recognition of their morphology may help in the selection of appropriate tumours for genetic testing.
authors.affiliation: Department of Pathology, Yale School of Medicine, 310 Cedar Street, New Haven, CT06520, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Finkelstein
authors.forename: Gillian H
authors.initials: GH
authors.lastname: Levy
authors.forename: Pei
authors.initials: P
authors.lastname: Hui
authors.forename: Avinash
authors.initials: A
authors.lastname: Prasad
authors.forename: Renu
authors.initials: R
authors.lastname: Virk
authors.forename: David C
authors.initials: DC
authors.lastname: Chhieng
authors.forename: Tobias
authors.initials: T
authors.lastname: Carling
authors.forename: Sanziana A
authors.initials: SA
authors.lastname: Roman
authors.forename: Julie A
authors.initials: JA
authors.lastname: Sosa
authors.forename: Robert
authors.initials: R
authors.lastname: Udelsman
authors.forename: Constantine G
authors.initials: CG
authors.lastname: Theoharis
authors.forename: Manju L
authors.initials: ML
authors.lastname: Prasad
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D001483:Base Sequence; D002277:Carcinoma; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000473:pathology*; D002648:Child; D004252:DNA Mutational Analysis; D017931:DNA Primers; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D050505:Mutant Proteins / Q000235:genetics*; D020125:Mutation, Missense; D017354:Point Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology*; D055815:Young Adult
chemical_list: D017931:DNA Primers; D050505:Mutant Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf