Department of Pathology
Cancer Biology | Neoplasms | Pathology | Translational Medical Research
OBJECTIVE: In papillary thyroid carcinoma (PTC), while the role of BRAF is well established, the contribution of BRAF to epithelial-mesenchymal transition is not.
STUDY DESIGN/SETTING: To elucidate the relationship between BRAF, surrogates of epithelial-mesenchymal transition (Snail, E-cadherin) and established histopathologic prognosticators in papillary thyroid carcinoma.
SUBJECTS/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).
CONCLUSION: 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.
BRAF, E-cadherin, Snail, epithelial-mesenchymal transition, papillary thyroid carcinoma
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Am J Transl Res. 2016 Nov 15;8(11):5076-5086. eCollection 2016. Link to article on publisher's website
American journal of translational research
Mitchell B, Leone D, Yang S, Khan A, Mahalingam M, Dhingra J. (2016). BRAF and epithelial-mesenchymal transition in papillary thyroid carcinoma - challenging the roles of Snail and E-Cadherin. Open Access Articles. Retrieved from https://escholarship.umassmed.edu/oapubs/2991
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