title: BRAF and epithelial-mesenchymal transition in papillary thyroid carcinoma - challenging the roles of Snail and E-Cadherin?
abstract: OBJECTIVE
  In papillary thyroid carcinoma (PTC), while the role of BRAF is well established, the contribution of BRAF to epithelial-mesenchymal transition is not.
  
  
  METHODS
  To elucidate the relationship between BRAF, surrogates of epithelial-mesenchymal transition (Snail, E-cadherin) and established histopathologic prognosticators in papillary thyroid carcinoma.
  
  
  METHODS
  In this IRB approved cross-sectional study, 50 cases of archived annotated PTC samples were retrieved and immunohistochemically stained for Snail and E-cadherin protein. A semi-quantitative scoring system (incorporating proportion and intensity) was utilized.
  
  
  RESULTS
  Snail and E-cadherin expression were noted in 44% and 84% of BRAF mutant and, in 29% and 95% of BRAFWT samples, respectively. No statistically significant correlations were noted between Snail, E-cadherin and histopathologic prognosticators. However, a trend was noted between Snail expression and tumor size <5 cm (P=0.07). Statistically significant differences between BRAF mutant and BRAFWT samples were noted in the following groups: conventional (68% vs. 5%) and tall cell (32% vs. 0%) histopathologic variants, extrathyroidal extension (32% vs. 5%), infiltrative growth pattern (80% vs. 48%), presence of desmoplasia (72% vs. 29%), psammona bodies (48% vs. 10%), and cystic change (32% vs. 5%). Among follicular variant of papillary thyroid carcinoma compared to BRAF mutant samples, BRAFWT samples were more commonly of the encapsulated variety (52% vs. 4%), and microcarcinomas (29% vs. 0%) (P<0.001 and =0.007, respectively).
  
  
  CONCLUSIONS
  Our findings, supporting the utility of BRAF as a putative therapeutic target in PTC, suggest that the interaction between BRAF and epithelial-mesenchymal transition in papillary thyroid carcinoma is not through induction of the Snail/E-cadherin pathway.
authors.affiliation: University of Florida College of Medicine Gainesville, FL, USA.
authors.forename: Brendon
authors.initials: B
authors.lastname: Mitchell
authors.affiliation: Division of Graduate Medical Sciences, Boston University School of Medicine Boston, MA, USA.
authors.forename: Dominick
authors.initials: D
authors.lastname: Leone
authors.affiliation: Department of Pathology, Boston University School of Medicine Boston, MA, USA.
authors.forename: Shi
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Pathology, University of Massachusetts Medical School Worcester, MA, UK.
authors.forename: Ashraf
authors.initials: A
authors.lastname: Khan
authors.affiliation: Dermatopathology Section, Department of Pathology and Lab Medicine (113), VA Consolidated Laboratories 1400 VFW PKWY, West Roxbury, MA 02132, USA.
authors.forename: Meera
authors.initials: M
authors.lastname: Mahalingam
authors.affiliation: ENT Specialists, Inc. 825 Washington St # 310, Norwood, MA 02062, UK.
authors.forename: Jagdish
authors.initials: J
authors.lastname: Dhingra
keywords: BRAF; E-cadherin; Snail; epithelial-mesenchymal transition; papillary thyroid carcinoma