title: Correlation between the BRAF V600E mutation and tumor invasiveness in papillary thyroid carcinomas smaller than 20 millimeters: analysis of 1060 cases.
abstract: BACKGROUND
  Evaluation of the degree of neoplastic infiltration beyond the thyroid capsule remains a unique parameter that can be evaluated by histopathological examination to label a papillary thyroid carcinoma (PTC) of 20 mm or less in size as a pT1 or pT3 tumor.
  
  
  OBJECTIVE
  We correlated the BRAF V600E mutation with both clinical-pathological features and the degree of neoplastic infiltration to redefine the reliability of the actual system of risk stratification in a large selected group of PTCs smaller than 20 mm.
  
  
  METHODS
  The presence of BRAF mutations was examined in 1060 PTCs less than 20 mm divided into four degrees of neoplastic infiltration: 1) totally encapsulated; 2) not encapsulated without thyroid capsule invasion; 3) thyroid capsule invasion; and 4) extrathyroidal extension.
  
  
  RESULTS
  The overall frequency of the BRAF V600E mutation was 44.6%. In both univariate and multivariate analyses, BRAF mutations showed a strong association with PTC variants (classical and tall cell), tumor size (11-20 mm), multifocality, absence of tumor capsule, extrathyroidal extension, lymph node metastasis, higher American Joint Commission on Cancer stage, and younger patient age. In PTCs staged as pT1 with thyroid capsule invasion, the frequency of BRAF mutations was significantly higher than in pT1 tumors that did not invade the thyroid capsule (67.3 vs. 31.8%, respectively; P < 0.0001). No statistically significant difference in BRAF alterations was found between pT1 tumors with thyroid capsule invasion and pT3 tumors (67.3 and 67.5%, respectively).
  
  
  CONCLUSIONS
  We suggest that evaluation of BRAF status would be useful even in pT1 tumors to improve risk stratification and patient management, although follow-up data are necessary to confirm our speculations.
authors.affiliation: Department of Surgery, Division of Pathology, Via Roma, 57, 56126 Pisa, Italy. f.basolo@med.unipi.it
authors.forename: Fulvio
authors.initials: F
authors.lastname: Basolo
authors.forename: Liborio
authors.initials: L
authors.lastname: Torregrossa
authors.forename: Riccardo
authors.initials: R
authors.lastname: Giannini
authors.forename: Mario
authors.initials: M
authors.lastname: Miccoli
authors.forename: Cristiana
authors.initials: C
authors.lastname: Lupi
authors.forename: Elisa
authors.initials: E
authors.lastname: Sensi
authors.forename: Piero
authors.initials: P
authors.lastname: Berti
authors.forename: Rossella
authors.initials: R
authors.lastname: Elisei
authors.forename: Paolo
authors.initials: P
authors.lastname: Vitti
authors.forename: Angelo
authors.initials: A
authors.lastname: Baggiani
authors.forename: Paolo
authors.initials: P
authors.lastname: Miccoli
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics; D002291:Carcinoma, Papillary / Q000235:genetics / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D018698:Glutamic Acid / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D017354:Point Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012189:Retrospective Studies; D013964:Thyroid Neoplasms / Q000235:genetics / Q000473:pathology*; D047368:Tumor Burden / Q000235:genetics*; D014633:Valine / Q000235:genetics
chemical_list: D018698:Glutamic Acid; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D014633:Valine