The Cancer Genome Atlas Validation of Ancillary Tests for Classifying Papillary Thyroid Carcinoma

ABSTRACT

BACKGROUND AND OBJECTIVES: Ancillary tests such as BRAF(V600E) mutation or immunohistochemical (IHC) assays have been utilized as complements to morphological criteria in diagnosing subsets of papillary thyroid carcinoma (PTC). Utilizing results from analysis by The Cancer Genome Atlas (TCGA), we evaluated the diagnostic value and feasibility of these ancillary tests in diagnosing follicular variant PTC (FVPTC). MATERIALS AND METHODS: Clinical data and tissue samples were analyzed from 370 PTC patients, who had undergone thyroidectomy between December 2003 and July 2014. PTC was limited to conventional PTC (CVPTC), tall cell variant PTC (TCPTC), and FVPTC. Using multivariate analyses, FVPTC cases were compared to CVPTC and TCPTC cases. Surgical specimens were pyrosequenced for BRAF(V600E) mutation or stained for IHC markers such as CD56, galectin-3, cytokeratin 19 (CK19), or CD31. For the validation, a comprehensive analysis was performed for BRAF(V600E) mutation and quantitative mRNA expressional difference in TCGA. RESULTS: Demographic differences were not observed between 159 CVPTC, 103 TCPTC, and 108 FVPTC cases. BRAF(V600E) mutation predominated in CVPTC+TCPTC group, but not in FVPTC group (78.4% vs. 18.7%, p<0.001), as suggested by TCGA (57.4% vs. 12.1%, p<0.0001). IHC markers significantly distinguished FVPTC cases from CVPTC+TCPTC cases. CD56 exhibited more intense staining in FVPTC cases (21.1% vs. 72.0%, p<0.001). Galectin-3 and CK19 yielded limited values. CD31 correlated with lymphovascular invasion (r=0.847, p<0.001). In analysis of TCGA, mRNA differential expression of these genes revealed their corresponding upregulation or downregulation. CONCLUSION: BRAF(V600E) mutation or TCGA-validated IHC assay could be recommended as ancillary tests for classifying PTC.