EP36 – Panel of microRNAs expressed in FNAB material of thyroid nodules and its application as molecular test

      Ferraz, Carolina1; Bittar, Gustavo1; Paschke, Ralf2; Eszlinger, Markus3; Padovani, Rosália1,4 1 Endocrinology Unit, Internal Medicine Department of Santa Casa de Sao Paulo, School of Medical Sciences, Sao Paulo, Brazil 2 Departments of Medicine, Oncology, and Biochemistry and Molecular Biology, & Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, Canada 3 Department of Oncology & Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, Canada 4 Nuclear Medicine Service of Santa Casa de Sao Paulo, School of Medical Sciences, Sao Paulo, Brazil   Background: Thyroid cancer (TC) is the most common endocrine neoplasm and fine needle aspiration biopsy (FNAB) is the gold standard for evaluating thyroid nodules1. However, 25-30% of all FNABs cannot distinguish between malignant and benign lesions, being therefore classified as “indeterminate”1. Molecular markers have been shown to play an important role in solving this problem2. MicroRNAs (miR) may act as possible molecular markers3 Methods: Through literature search and prior data from our cooperative group4, 6 miRs were chosen to compose a panel and their expression profiles were evaluated in 11 FNAB samples (2 benign, 3 AUS/FLUS, 2 folicular neoplasm and 4 papilary carcinoma) by RT-qPCR in order to distinguish benign from malignant samples. Final histology was used to validate the panel. Results: The final panel was composed of miR-146b,-221,-222,-484,-139-5p, and -145-5p. MiR-146b showed a high sensitivity (80%) and specificity (75%) to differentiate malignant from benign nodules. Other miRs, when evaluated separately, did not present a significant value for differentiating samples. The 2 benign FNAB samples showed an occult microcarcinoma at final histology and showed a significant miR-146b overexpression. Discussion/Conclusion:  In our preliminary analysis, previous data with regard to the role of miR-146b as molecular marker were confirmed5. Although the expression of the other miRs did not present differential expression in malignant tissues, an evaluation of a larger number of samples could improve statistical analysis and clarify their role as molecular markers in TC. Interestingly, miR-146b showed an overexpression in occult microcarcinomas in 2 benign FNAB samples.   References:
    1. Gharib H, Papini E, Paschke R, Duick DS, Valcavi R, Hegedus L,Vitti P American Association of Clinical Endocrinologists, Associazione Medici Endocrinologi, and European Thyroid Association medical guidelines for clinical practice for the diagnosis and management of thyroid nodules. Endocr Pract 2010. 16(Suppl 1):1–43
    2. Haugen BR, et al. The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid 2016. Volume 26, Number 1.
    3. Haggi Mazeh, MicroRNA as a Diagnostic Tool in Fine-Needle Aspiration Biopsy of Thyroid Nodules. The Oncologist 2012.17:1032–1038.
    4. Tomasz Stokowy, Bartosz Wojtas, Jolanta Krajewska, Ewa Stobiecka, Henning Dralle, Thomas Musholt, Steffen Hauptmann, Dariusz Lange, László Hegedu?s, Barbara Jarza, Knut Krohn, Ralf Paschke, Markus Eszlinger; A two miRNA classifier differentiates follicular thyroid carcinomas from follicular thyroid adenomas. Molecular and Cellular Endocrinology Volume 399, 5:43–49.
    5. Menno R. Vriens, Julie Weng, Insoo Suh, Nhung Huynh, Marlon A. Guerrero, Wen T. Shen, Quan-Yang Duh, Orlo H. Clark, Electron Kebebew, MicroRNA Expression Profiling Is a Potential Diagnostic Tool for Thyroid Cancer. Cancer 2012. 3426-3432.


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