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- Title
340 MicroRNA Expression Profiling Differentiated Parathyroid Lesions.
- Authors
Torres, Maria; Narick, Christina; Jackson, Sara; Silverman, Jan; Finkelstein, Sydney
- Abstract
Introduction: Thyroid nodules frequently undergo fine needle aspiration (FNA) to discriminate between benign vs malignant disease. Parathyroid processes in the form of hyperplasia (PH), adenoma (PA), and carcinoma (PC) can mimic thyroid nodular disease cytologically leading to indeterminate diagnosis. Molecular analysis, based on mutational analysis and/or RNA expression profiling, and designed for thyroid neoplasia, is often used as an ancillary tool. We sought discriminating features in thyroid molecular testing that would identify parathyroid tissue and indicate specific parathyroid disease states. Methods: Eight FFPE tissue specimens representing pairs of normal, hyperplastic, adenomatous, and carcinomatous parathyroid lesions underwent combined mutational and microRNA expression profiling designed to differentiate thyroid neoplasia. Mutational analysis targeted common thyroid mutations (BRAF, HRAS, KRAS, NRAS, PIK3CA, PAX8/PPAR, and RET/PTC translocation) on a next-generation sequencing platform (Illumina). MicroRNA (miR) expression profiling targeted 10 specific miRs showing over and under expression in thyroid follicular cell neoplasia. Messenger RNA expression of PAX8 and NKX2.1, unique to thyroid follicular cells, was used as markers for thyroid origin of nucleic acid. Results: Microdissected FFPE yielded adequate nucleic acid for this thyroid molecular testing approach. All parathyroid specimens lacked messenger RNA expression of PAX8 and NKX2.1, indicating absence of thyroid follicle lining cells. None of these parathyroid specimens manifest common somatic mutations seen in thyroid neoplasia. miR expression profiling, using criteria applied to thyroid follicular neoplasia, would have indicated thyroid malignancy if inappropriately assumed to be thyroid. Specific relative miR expression levels differentiated each of the parathyroid states. Normal parathyroid underexpressed miR138. PH underexpressed miR31, 204, and 551. PA overexpressed miR29b, 146, and 375. PC showed hyperexpression of miR31, 204, and 551. Conclusion: Parathyroid lesion can confound FNA cytology diagnosis of nodules presumed to be of thyroid origin. In this initial study ancillary molecular testing can affirm parathyroid tissue origin (messenger RNA expression) and miR expression profiling appears capable of differentiating between parathyroid disease states supporting further confirmatory studies. The approach is effective on fixative-treated specimens.
- Subjects
MICRORNA; CELL proliferation
- Publication
American Journal of Clinical Pathology, 2018, Vol 149, pS146
- ISSN
0002-9173
- Publication type
Article
- DOI
10.1093/ajcp/aqx127.339