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The Cancer Genome Atlas Validation of Ancillary Tests for Classifying Papillary Thyroid Carcinoma
Int J Thyroidol 2017;10(1):24-35
Published online May 30, 2017;  https://doi.org/10.11106/ijt.2017.10.1.24
© 2017 Korean Thyroid Association.

Yong Joon Suh1,2, Hyoun Jong Moon2, Ji-Young Choe3 and Hyo Jin Park4

Department of Surgery, Hallym University Sacred Heart Hospital, Hallym University College of Medicine1, Anyang, Cancer Research Institute, Myongji Hospital2, Goyang, Department of Pathology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine3, Anyang, Department of Pathology, Seoul National University Bundang Hospital4, Seongnam, Korea
Correspondence to: Yong Joon Suh, MD, CPBMI, Cancer Research Institute, Myongji Hospital, 55 Hwasu-ro 14beon-gil, Deokyang-gu, Goyang 10475, Korea
Tel: 82-31-810-5427, Fax: 82-31-969-0500, E-mail: nicizm@gmail.com
Received November 25, 2016; Revised February 15, 2017; Accepted February 20, 2017.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background and Objectives: Ancillary tests such as BRAFV600E 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 BRAFV600E 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 BRAFV600E mutation and quantitative mRNA expressional difference in TCGA. Results: Demographic differences were not observed between 159 CVPTC, 103 TCPTC, and 108 FVPTC cases. BRAFV600E 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: BRAFV600E mutation or TCGA-validated IHC assay could be recommended as ancillary tests for classifying PTC.
Keywords : BRAF, Immunohistochemistry marker, Thyroid neoplasm, Follicular variant papillary thyroid carcinoma, TCGA