Molecular Signature of Indeterminate Thyroid Lesions: Current Methods to Improve Fine Needle Aspiration Cytology (FNAC) Diagnosis

Silvia Cantara, Carlotta Marzocchi, Tania Pilli, Sandro Cardinale, Raffaella Forleo, Maria Grazia Castagna, Furio Pacini, Silvia Cantara, Carlotta Marzocchi, Tania Pilli, Sandro Cardinale, Raffaella Forleo, Maria Grazia Castagna, Furio Pacini

Abstract

Fine needle aspiration cytology (FNAC) represents the gold standard for determining the nature of thyroid nodules. It is a reliable method with good sensitivity and specificity. However, indeterminate lesions remain a diagnostic challenge and researchers have contributed molecular markers to search for in cytological material to refine FNAC diagnosis and avoid unnecessary surgeries. Nowadays, several "home-made" methods as well as commercial tests are available to investigate the molecular signature of an aspirate. Moreover, other markers (i.e., microRNA, and circulating tumor cells) have been proposed to discriminate benign from malignant thyroid lesions. Here, we review the literature and provide data from our laboratory on mutational analysis of FNAC material and circulating microRNA expression obtained in the last 6 years.

Keywords: fine needle aspiration cytology (FNAC); gene expression classifier; indeterminate lesions; microRNAs (miRNAs); next generation sequencing.

Conflict of interest statement

The authors declare no conflict of interest.

References

    1. Aschebrook-Kilfoy B., Ward M.H., Sabra M.M., Devesa S.S. Thyroid cancer incidence patterns in the United States by histologic type, 1992–2006. Thyroid. 2011;21:125–134. doi: 10.1089/thy.2010.0021.
    1. Belfiore A., La Rosa G.L., La Porta G.A., Giuffrida D., Milazzo G., Lupo L., Regalbuto C., Vigneri R. Cancer risk in patients with cold thyroid nodules: Relevance of iodine intake, sex, age, and multinodularity. Am. J. Med. 1992;93:363–369. doi: 10.1016/0002-9343(92)90164-7.
    1. Gharib H., Goellner J.R., Johnson D.A. Fine needle aspiration of the thyroid. A 12 year experience with 11,000 biopsies. Clin. Lab. Med. 1993;13:699–709.
    1. Bongiovanni M., Spitale A., Faquin W.C., Mazzucchelli L., Baloch Z.W. The Bethesda System for Reporting Thyroid Cytopathology: A meta-analysis. Acta Cytol. 2012;56:333–339. doi: 10.1159/000339959.
    1. Hamming J.F., Goslings B.M., Van Steenis G.J., van Ravenswaay Claasen H., Hermans J., van de Velde C.J.H. The value of one-needle aspiration biopsy in patients with nodular thyroid disease divided into groups of suspicion of malignant neoplasms on clinical grounds. Arch. Intern. Med. 1990;150:113–116. doi: 10.1001/archinte.1990.00390130107016.
    1. Caruso D., Mazzaferri E.L. Fine-needle aspiration in the management of thyroid nodules. Endocrinologist. 1991;1:194–202. doi: 10.1097/00019616-199106000-00009.
    1. Caplan R.H., Kisken W.A., Strutt P.J., Wester S.M. Fine-needle aspiration biopsy of thyroid nodules: A cost-effective diagnostic plan. Postgrad. Med. 1991;90:183–190. doi: 10.1080/00325481.1991.11700990.
    1. Hamburger J.I. Extensive personal experience. Diagnosis of thyroid nodules by fine needle biopsy: Use and abuse. JCEM. 1994;79:335–339.
    1. Yoshii T., Inohara H., Takenaka Y., Honjo Y., Akahani S., Nomura T., Raz A., Kubo T. Galectin-3 maintains the transformed phenotype of thyroid papillary carcinoma cells. Int. J. Oncol. 2001;18:787–792. doi: 10.3892/ijo.18.4.787.
    1. Sapio M.R., Guerra A., Posca D., Limone P.P., Deandrea M., Motta M., Troncone G., Caleo A., Vallefuoco P., Rossi G., et al. Combined analysis of galectin-3 and BRAFV600E improves the accuracy of fine-needle aspiration biopsy with cytological findings suspicious for papillary thyroid carcinoma. Endocr. Relat. Cancer. 2007;14:1089–1097. doi: 10.1677/ERC-07-0147.
    1. Bryson P.C., Shores C.G., Hart C., Thorne L., Patel M.R., Richey L., Farag A., Zanation A.M. Immunohistochemical distinction of follicular thyroid adenomas and follicular carcinomas. Arch. Otolaryngol. Head Neck Surg. 2008;134:581–586. doi: 10.1001/archotol.134.6.581.
    1. Torregrossa L., Faviana P., Filice M.E., Materazzi G., Miccoli P., Vitti P., Fontanini G., Melillo R.M., Santoro M., Basolo F. CXC chemokine receptor 4 immunodetection in the follicular variant of papillary thyroid carcinoma: Comparison to galectin-3 and hector battifora mesothelial cell-1. Thyroid. 2010;20:495–504. doi: 10.1089/thy.2009.0282.
    1. Saggiorato E., de Pompa R., Volante M., Cappia S., Arecco F., Dei Tos A.P., Orlandi F., Papotti M. Characterization of thyroid ‘follicular neoplasms’ in fine-needle aspiration cytological specimens using a panel of immunohistochemical markers: A proposal for clinical application. Endocr. Relat. Cancer. 2005;12:305–317. doi: 10.1677/erc.1.00944.
    1. Raggio E., Camandona M., Solerio D., Martino P., Franchello A., Orlandi F., Gasparri G. The diagnostic accuracy of the immunocytochemical markers in the pre-operative evaluation of follicular thyroid lesions. J. Endocrinol. Investig. 2010;33:378–381. doi: 10.1007/BF03346607.
    1. Bartolazzi A., Gasbarri A., Papotti M., Bussolati G., Lucante T., Khan A., Inohara H., Marandino F., Orlandi F., Nardi F., et al. Application of an immunodiagnostic method for improving preoperative diagnosis of nodular thyroid lesions. Lancet. 2001;357:1644–1650. doi: 10.1016/S0140-6736(00)04817-0.
    1. Zhang L., Krausz T., DeMay R.M. A pilot study of galectin-3, HBME-1, and p27 triple immunostaining pattern for diagnosis of indeterminate thyroid nodules in cytology with correlation to histology. Appl. Immunohistochem. Mol. Morphol. 2015;23:481–490. doi: 10.1097/PAI.0000000000000106.
    1. Carpi A., Naccarato A.G., Iervasi G., Nicolini A., Bevilacqua G., Viacava P., Collecchi P., Lavra L., Marchetti C., Sciacchitano S., et al. Large needle aspiration biopsy and galectin-3 determination in selected thyroid nodules with indeterminate FNA-cytology. Br. J. Cancer. 2006;95:204–209. doi: 10.1038/sj.bjc.6603232.
    1. Franco C., Martínez V., Allamand J.P., Medina F., Glasinovic A., Osorio M., Schachter D. Molecular markers in thyroid fine-needle aspiration biopsy: A prospective study. Appl. Immunohistochem. Mol. Morphol. 2009;17:211–215. doi: 10.1097/PAI.0b013e31818935a9.
    1. Das D.K., Al-Waheeb S.K., George S.S., Haji B.I., Mallik MK. Contribution of immunocytochemical stainings for galectin-3, CD44, and HBME1 to fine-needle aspiration cytology diagnosis of papillary thyroid carcinoma. Diagn. Cytopathol. 2014;42:498–505. doi: 10.1002/dc.23062.
    1. Trimboli P., Guidobaldi L., Amendola S., Nasrollah N., Romanelli F., Attanasio D., Ramacciato G., Saggiorato E., Valabrega S., Crescenzi A. Galectin-3 and HBME-1 improve the accuracy of core biopsy in indeterminate thyroid nodules. Endocrine. 2016;52:39–45. doi: 10.1007/s12020-015-0678-7.
    1. Naor D., Sionov R.V., Ish-Shalom D. CD44: Structure, function, and association with the malignant process. Adv. Cancer Res. 1997;71:241–319.
    1. Günthert U., Hofmann M., Rudy W., Reber S., Zöller M., Haussmann I., Matzku S., Wenzel A., Ponta H., Herrlich P. A new variant of glycoprotein CD44 confers metastatic potential to rat carcinoma cells. Cell. 1991;65:13–24. doi: 10.1016/0092-8674(91)90403-L.
    1. Matesa N., Samija I., Kusić Z. Accuracy of fine needle aspiration biopsy with and without the use of tumor markers in cytologically indeterminate thyroid lesions. Coll. Antropol. 2010;34:53–57.
    1. Maruta J., Hashimoto H., Yamashita H., Yamashita H., Noguchi S. Immunostaining of galectin-3 and CD44v6 using fine-needle aspiration for distinguishing follicular carcinoma from adenoma. Diagn. Cytopathol. 2004;31:392–396. doi: 10.1002/dc.20156.
    1. Haugen B.R., Alexander E.K., Bible K.C., Doherty G.M., Mandel S.J., Nikiforov Y.E., Pacini F., Randolph G.W., Sawka A.M., Schlumberger M., et al. 2015 American thyroid association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: The American thyroid association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid. 2016;26:1–133. doi: 10.1089/thy.2015.0020.
    1. Sobrinho-Simões M., Máximo V., Rocha A.S., Trovisco V., Castro P., Preto A., Lima J., Soares P. Intragenic mutations in thyroid cancer. Endocrinol. Metab. Clin. N. Am. 2008;37:333–362. doi: 10.1016/j.ecl.2008.02.004.
    1. Xing M. Molecular pathogenesis and mechanisms of thyroid cancer. Nat. Rev. Cancer. 2013;13:184–199. doi: 10.1038/nrc3431.
    1. Nikiforova M.N., Kimura E.T., Gandhi M., Biddinger P.W., Knauf J.A., Basolo F., Zhu Z., Giannini R., Salvatore G., Fusco A., et al. BRAF mutations in thyroid tumors are restricted to papillary carcinomas and anaplastic or poorly differentiated carcinomas arising from papillary carcinomas. J. Clin. Endocrinol. Metab. 2003;88:5399–5404. doi: 10.1210/jc.2003-030838.
    1. Vinagre J., Almeida A., Pópulo H., Batista R., Lyra J., Pinto V., Coelho R., Celestino R., Prazeres H., Lima L., et al. Frequency of TERT promoter mutations in human cancers. Nat. Commun. 2013;4:2185. doi: 10.1038/ncomms3185.
    1. Melo M., da Rocha A.G., Vinagre J., Batista R., Peixoto J., Tavares C., Celestino R., Almeida A., Salgado C., Eloy C., et al. TERT promoter mutations are a major indicator of poor outcome in differentiated thyroid carcinomas. J. Clin. Endocrinol. Metab. 2014;99:E754–E765. doi: 10.1210/jc.2013-3734.
    1. Ohori N.P., Nikiforova M.N., Schoedel K.E., LeBeau S.O., Hodak S.P., Seethala R.R., Carty S.E., Ogilvie J.B., Yip L., Nikiforov Y.E. Contribution of molecular testing to thyroid fine-needle aspiration cytology of “follicular lesion of undetermined significance/atypia of undetermined significance”. Cancer Cytopathol. 2010;118:17–23. doi: 10.1002/cncy.20063.
    1. Cantara S., Capezzone M., Marchisotta S., Capuano S., Busonero G., Toti P., Di Santo A., Caruso G., Carli A.F., Brilli L., et al. Impact of proto-oncogene mutation detection in cytological specimens from thyroid nodules improves the diagnostic accuracy of cytology. JCEM. 2010;95:1365–1369. doi: 10.1210/jc.2009-2103.
    1. Nikiforov Y.E., Ohori N.P., Hodak S.P., Carty S.E., LeBeau S.O., Ferris R.L., Yip L., Seethala R.R., Tublin M.E., Stang M.T., et al. Impact of mutational testing on the diagnosis and management of patients with cytologically indeterminate thyroid nodules: A prospective analysis of 1056 FNA samples. JCEM. 2011;96:3390–3397. doi: 10.1210/jc.2011-1469.
    1. Chudova D., Wilde J.I., Wang E.T., Wang H., Rabbee N., Egidio C.M., Reynolds J., Tom E., Pagan M., Rigl C.T., et al. Molecular classification of thyroid nodules using high-dimensionality genomic data. JCEM. 2010;95:5296–5304. doi: 10.1210/jc.2010-1087.
    1. Alexander E.K., Kennedy G.C., Baloch Z.W., Cibas E.S., Chudova D., Diggans J., Friedman L., Kloos R.T., LiVolsi V.A., Mandel S.J., et al. Preoperative diagnosis of benign thyroid nodules with indeterminate cytology. N. Eng. J. Med. 2012;367:705–715. doi: 10.1056/NEJMoa1203208.
    1. Alexander E.K., Schorr M., Klopper J., Kim C., Sipos J., Nabhan F., Parker C., Steward D.L., Mandel S.J., Haugen B.R. Multicenter clinical experience with the Afirma gene expression classifier. JCEM. 2014;99:119–125. doi: 10.1210/jc.2013-2482.
    1. Harrell R.M., Bimston D.N. Surgical utility of Afirma: Effects of high cancer prevalence and oncocytic cell types in patients with indeterminate thyroid cytology. Endocr. Pract. 2014;20:364–369. doi: 10.4158/EP13330.OR.
    1. Lastra R.R., Pramick M.R., Crammer C.J., LiVolsi V.A., Baloch Z.W. Implications of a suspicious afirma test result in thyroid fine-needle aspiration cytology: An institutional experience. Cancer Cytopathol. 2014;122:737–744. doi: 10.1002/cncy.21455.
    1. Marti J.L., Avadhani V., Donatelli L.A., Niyogi S., Wang B., Wong R.J., Shaha A.R., Ghossein R.A., Lin O., Morris L.G., et al. Wide inter-institutional variation in performance of a molecular classifier for indeterminate thyroid nodules. Ann. Surg. Oncol. 2015;22:3996–4001. doi: 10.1245/s10434-015-4486-3.
    1. McIver B., Castro M.R., Morris J.C., Bernet V., Smallridge R., Henry M., Kosok L., Reddi H. An independent study of a gene expression classifier (Afirma) in the evaluation of cytologically indeterminate thyroid nodules. JCEM. 2014;99:4069–4077. doi: 10.1210/jc.2013-3584.
    1. Nikiforova M.N., Wald A.I., Roy S., Durso M.B., Nikiforov Y.E. Targeted next-generation sequencing panel (ThyroSeq) for detection of mutations in thyroid cancer. JCEM. 2013;98:E1852–E1860. doi: 10.1210/jc.2013-2292.
    1. Beaudenon-Huibregtse S., Alexander E.K., Guttler R.B., Hershman J.M., Babu V., Blevins T.C., Moore P., Andruss B., Labourier E. Centralized molecular testing for oncogenic gene mutations complements the local cytopathologic diagnosis of thyroid nodules. Thyroid. 2014;24:1479–1487. doi: 10.1089/thy.2013.0640.
    1. Eszlinger M., Krogdahl A., Münz S., Rehfeld C., Precht Jensen E.M., Ferraz C., Bösenberg E., Drieschner N., Scholz M., Hegedüs L., et al. Impact of molecular screening for point mutations and rearrangements in routine air-dried fine-needle aspiration samples of thyroid nodules. Thyroid. 2014;24:305–313. doi: 10.1089/thy.2013.0278.
    1. Nikiforov Y.E., Carty S.E., Chiosea S.I., Coyne C., Duvvuri U., Ferris R.L., Gooding W.E., Hodak S.P., LeBeau S.O., Ohori N.P., et al. Highly accurate diagnosis of cancer in thyroid nodules with follicular neoplasm/suspicious for a follicular neoplasm cytology by ThyroSeq v2 next-generation sequencing assay. Cancer. 2014;120:3627–3634. doi: 10.1002/cncr.29038.
    1. Coco S., Truini A., Vanni I., Dal Bello M.G., Alama A., Rijavec E., Genova C., Barletta G., Sini C., Burrafato G., et al. Next generation sequencing in non-small cell lung cancer: New avenues toward the personalized medicine. Curr. Drug Targets. 2015;16:47–59. doi: 10.2174/1389450116666141210094640.
    1. Malapelle U., Vigliar E., Sgariglia R., Bellevicine C., Colarossi L., Vitale D., Pallante P., Troncone G. Ion Torrent next-generation sequencing for routine identification of clinically relevant mutations in colorectal cancer patients. J. Clin. Pathol. 2015;68:64–68. doi: 10.1136/jclinpath-2014-202691.
    1. Chevrier S., Arnould L., Ghiringhelli F., Coudert B., Fumoleau P., Boidot R. Next-generation sequencing analysis of lung and colon carcinomas reveals a variety of genetic alterations. Int. J. Oncol. 2014;45:1167–1174. doi: 10.3892/ijo.2014.2528.
    1. Ross J.S., Badve S., Wang K., Sheehan C.E., Boguniewicz A.B., Otto G.A., Yelensky R., Lipson D., Ali S., Morosini D., et al. Genomic profiling of advanced-stage, metaplastic breast carcinoma by next-generation sequencing reveals frequent, targetable genomic abnormalities and potential new treatment options. Arch. Pathol. Lab. Med. 2015;139:642–649. doi: 10.5858/arpa.2014-0200-OA.
    1. Roy S., Durso M.B., Wald A., Nikiforov Y.E., Nikiforova M.N. SeqReporter: Automating next-generation sequencing result interpretation and reporting workflow in a clinical laboratory. J. Mol. Diagn. 2014;16:11–22. doi: 10.1016/j.jmoldx.2013.08.005.
    1. Le Mercier M., D'Haene N., de Nève N., Blanchard O., Degand C., Rorive S., Salmon I. Next-generation sequencing improves the diagnosis of thyroid FNA specimens with indeterminate cytology. Histopathology. 2015;66:215–224. doi: 10.1111/his.12461.
    1. Carthew R.W., Sontheimer E.J. Origins and Mechanisms of miRNAs and siRNAs. Cell. 2009;136:642–655. doi: 10.1016/j.cell.2009.01.035.
    1. Mitchell P.S., Parkin R.K., Kroh E.M., Fritz B.R., Wyman S.K., Pogosova-Agadjanyan E.L., Peterson A., Noteboom J., O’Briant K.C., Allen A., et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc. Natl. Acad. Sci. USA. 2008;105:10513–10518. doi: 10.1073/pnas.0804549105.
    1. Chen X., Ba Y., Ma L., Cai X., Yin Y., Wang K., Guo J., Zhang Y., Chen J., Guo X., et al. Characterization of microRNAs in serum: A novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 2008;18:997–1006. doi: 10.1038/cr.2008.282.
    1. Lawrie C.H., Gal S., Dunlop H.M., Pushkaran B., Liggins A.P., Pulford K., Banham A.H., Pezzella F., Boultwood J., Wainscoat J.S., et al. Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Br. J. Haematol. 2008;141:672–675. doi: 10.1111/j.1365-2141.2008.07077.x.
    1. Taylor D.D., Gercel-Taylor C. MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol. Oncol. 2008;110:13–21. doi: 10.1016/j.ygyno.2008.04.033.
    1. Lu J., Getz G., Miska E.A., Alvarez-Saavedra E., Lamb J., Peck D., Sweet-Cordero A., Ebert B.L., Mak R.H., Ferrando A.A., et al. MicroRNA expression profiles classify human cancers. Nature. 2005;435:834–838. doi: 10.1038/nature03702.
    1. Volinia S., Calin G.A., Liu C.G., Ambs S., Cimmino A., Petrocca F., Visone R., Iorio M., Roldo C., Ferracin M., et al. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc. Natl. Acad. Sci. USA. 2006;103:2257–2261. doi: 10.1073/pnas.0510565103.
    1. Tetzlaff M.T., Liu A., Xu X., Master S.R., Baldwin D.A., Tobias J.W., Livolsi V.A., Baloch Z.W. Differential expression of miRNAs in papillary thyroid carcinoma compared to multinodular goiter using formalin fixed paraffin embedded tissues. Endocr. Pathol. 2007;18:163–173. doi: 10.1007/s12022-007-0023-7.
    1. Chen Y.T., Kitabayashi N., Zhou X.K., Fahey T.J., 3rd, Scognamiglio T. MicroRNA analysis as a potential diagnostic tool for papillary thyroid carcinoma. Mod. Pathol. 2008;21:1139–1146. doi: 10.1038/modpathol.2008.105.
    1. He H., Jazdzewski K., Li W., Liyanarachchi S., Nagy R., Volinia S., Calin G.A., Liu C.G., Franssila K., Suster S., et al. The role of microRNA genes in papillary thyroid carcinoma. Proc. Natl. Acad. Sci. USA. 2005;102:19075–19080. doi: 10.1073/pnas.0509603102.
    1. Nikifororva M.N., Tseng G.C., Steward D., Diorio D., Nikiforov Y. MicroRNA expression profiling of thyroid tumors: Biological significance and diagnostic utility. JCEM. 2008;93:1600–1608.
    1. Swierniak M., Wojcicka A., Czetwertynska M., Stachlewska E., Maciag M., Wiechno W., Gornicka B., Bogdanska M., Koperski L., de la Chapelle A., et al. In-depth characterization of the microRNA transcriptome in normal thyroid and papillary thyroid carcinoma. JCEM. 2013;98:E1401–E1409. doi: 10.1210/jc.2013-1214.
    1. Mancikova V., Castelblanco E., Pineiro-Yanez E., Perales-Paton J., de Cubas A.A., Inglada-Perez L., Matias-Guiu X., Capel I., Bella M., Lerma E., et al. MicroRNA deep-sequencing reveals master regulators of follicular and papillary thyroid tumors. Mod. Pathol. 2015;28:748–757. doi: 10.1038/modpathol.2015.44.
    1. Kitano M., Rahbari R., Patterson E.E., Xiong Y., Prasad N.B., Wang Y., Zeiger M.A., Kebebew E. Expression profiling of difficult-to-diagnose thyroid histologic subtypes shows distinct expression profiles and identify candidate diagnostic microRNAs. Ann. Surg. Oncol. 2011;18:3443–3452. doi: 10.1245/s10434-011-1766-4.
    1. Yip L., Kelly L., Shuai Y., Armstrong M.J., Nikiforov Y.E., Carty S.E., Nikiforova M.N. MicroRNA signature distinguishes the degree of aggressiveness of papillary thyroid carcinoma. Ann. Surg. Oncol. 2011;18:2035–2041. doi: 10.1245/s10434-011-1733-0.
    1. Mazeh H., Levy Y., Mizrahi I., Appelbaum L., Ilyayev N., Halle D., Freund H.R., Nissan A. Differentiating benign from malignant thyroid nodules using micro ribonucleic acid amplification in residual cells obtained by fine needle aspiration biopsy. J. Surg. Res. 2013;180:216–221. doi: 10.1016/j.jss.2012.04.051.
    1. Agretti P., Ferrarini E., Rago T., Candelieri A., de Marco G., Dimida A., Niccolai F., Molinaro A., Di Coscio G., Pinchera A., et al. MicroRNA expression profile helps to distinguish benign nodules from papillary thyroid carcinomas starting from cells of fine-needle aspiration. Eur. J. Endocrinol. 2012;167:393–400. doi: 10.1530/EJE-12-0400.
    1. Wei W.J., Shen C.T., Song H.J., Qiu Z.L., Luo Q.Y. MicroRNAs as a potential tool in the differential diagnosis of thyroid cancer: A systematic review and meta-analysis. Clin. Endocrinol. 2016;84:127–133. doi: 10.1111/cen.12696.
    1. Kitano M., Rahbari R., Patterson E.E., Steinberg S.M., Prasad N.B., Wang Y., Zeiger M.A., Kebebew E. Evaluation of candidate diagnostic microRNAs in thyroid fine-needle aspiration biopsy samples. Thyroid. 2012;22:285–291. doi: 10.1089/thy.2011.0313.
    1. Keutgen X.M., Filicori F., Crowley M.J., Wang Y., Scognamiglio T., Hoda R., Buitrago D., Cooper D., Zeiger M.A., Zarnegar R., et al. A panel of four miRNAs accurately differentiates malignant from benign indeterminate thyroid lesions on fine needle aspiration. Clin. Cancer Res. 2012;18:2032–2038. doi: 10.1158/1078-0432.CCR-11-2487.
    1. Mazeh H., Mizrahi I., Halle D., Ilyayev N., Stojadinovic A., Trink B., Mitrani-Rosenbaum S., Roistacher M., Ariel I., Eid A., et al. Development of a microRNA-based molecular assay for the detection of papillary thyroid carcinoma in aspiration biopsy samples. Thyroid. 2011;21:111–118. doi: 10.1089/thy.2010.0356.
    1. Panebianco F., Mazzanti C., Tomei S., Aretini P., Franceschi S., Lessi F., Di Coscio G., Bevilacqua G., Marchetti I. The combination of four molecular markers improves thyroid cancer cytologic diagnosis and patient management. BMC Cancer. 2015;19:918. doi: 10.1186/s12885-015-1917-2.
    1. Vriens M.R., Weng J., Suh I., Huynh N., Guerrero M.A., Shen W.T., Duh Q.Y., Clark O.H., Kebebew E. MicroRNA expression profiling is a potential diagnostic tool for thyroid cancer. Cancer. 2012;118:3426–3432. doi: 10.1002/cncr.26587.
    1. Ludvíková M., Kalfeřt D., Kholová I. Pathobiology of MicroRNAs and Their Emerging Role in Thyroid Fine-Needle Aspiration. Acta Cytol. 2015;59:435–444. doi: 10.1159/000442145.
    1. Lee Y.S., Lim Y.S., Lee J.C., Wang S.G., Park H.Y., Kim S.Y., Lee B.J. Differential expression levels of plasma-derived miR-146b and miR-155 in papillary thyroid cancer. Oral Oncol. 2015;51:77–83. doi: 10.1016/j.oraloncology.2014.10.006.
    1. Yu S., Liu Y., Wang J., Guo Z., Zhang Q., Yu F., Zhang Y., Huang K., Li Y., Song E., et al. Circulating microRNA profiles as potential biomarkers for diagnosis of papillary thyroid carcinoma. JCEM. 2012;97:2084–2092. doi: 10.1210/jc.2011-3059.
    1. Cantara S., Pilli T., Sebastiani G., Cevenini G., Busonero G., Cardinale S., Dotta F., Pacini F. Circulating miRNA95 and miRNA190 are sensitive markers for the differential diagnosis of thyroid nodules in a Caucasian population. JCEM. 2014;99:4190–4198. doi: 10.1210/jc.2014-1923.
    1. Lithwick-Yanai G., Dromi N., Shtabsky A., Morgenstern S., Strenov Y., Feinmesser M., Kravtsov V., Leon M., Hajdúch M., Ali S.Z., et al. Multicentre validation of a microRNA-based assay for diagnosing indeterminate thyroid nodules utilising fine needle aspirate smears. J. Clin. Pathol. 2016 doi: 10.1136/jclinpath-2016-204089.
    1. Benjamin H., Schnitzer-Perlman T., Shtabsky A., VandenBussche C.J., Ali S.Z., Kolar Z., Pagni F., Rosetta Genomics Group. Bar D., Meiri E. Analytical validity of a microRNA-based assay for diagnosing indeterminate thyroid FNA smears from routinely prepared cytology slides. Cancer Cytopathol. 2016;124:711–721. doi: 10.1002/cncy.21731.
    1. Suriano R., Lin Y., Ashok B.T., Schaefer S.D., Schantz S.P., Geliebter J., Tiwari R.K. Pilot study using SELDI-TOF-MS based proteomic profile for the identification of diagnostic biomarkers of thyroid proliferative diseases. J. Proteome Res. 2006;5:856–861. doi: 10.1021/pr050349r.
    1. Torres-Cabala C., Bibbo M., Panizo-Santos A., Barazi H., Krutzsch H., Roberts D.D., Merino M.J. Proteomic identification of new biomarkers and application in thyroid cytology. Acta Cytol. 2006;50:518–528. doi: 10.1159/000326006.
    1. Brown L.M., Helmke S.M., Hunsucker S.W., Netea-Maier R.T., Chiang S.A., Heinz D.E., Shroyer K.R., Duncan M.W., Haugen B.R. Quantitative and qualitative differences in protein expression between papillary thyroid carcinoma and normal thyroid tissue. Mol. Carcinog. 2006;45:613–626. doi: 10.1002/mc.20193.
    1. Krause K., Karger S., Schierhorn A., Poncin S., Many M.C., Fuhrer D. Proteomic profiling of cold thyroid nodules. Endocrinology. 2007;148:1754–1763. doi: 10.1210/en.2006-0752.
    1. Puxeddu E., Susta F., Orvietani P.L., Chiasserini D., Barbi F., Moretti S., Cavaliere A., Santeusanio F., Avenia N., Binaglia L. Identification of differentially expressed proteins in papillary thyroid carcinomas with V600E mutation of BRAF. Proteom. Clin. Appl. 2007;1:672–680. doi: 10.1002/prca.200600776.
    1. Netea-Maier R.T., Hunsucker S.W., Hoevenaars B.M., Helmke S.M., Slootweg P.J., Hermus A.R., Haugen B.R., Duncan M.W. Discovery and validation of protein abundance differences between follicular thyroid neoplasms. Cancer Res. 2008;68:1572–1580. doi: 10.1158/0008-5472.CAN-07-5020.
    1. Musso R., di Cara G., Albanese N.N., Marabeti M.R., Cancemi P., Martini D., Orsini E., Giordano C., Pucci-Minafra I. Differential proteomic and phenotypic behaviour of papillary and anaplastic thyroid cell lines. J. Proteom. 2013;90:115–125. doi: 10.1016/j.jprot.2013.01.023.
    1. Chaker S., Kashat L., Voisin S., Kaur J., Kak I., MacMillan C., Ozcelik H., Siu K.W., Ralhan R., Walfish P.G. Secretome proteins as candidate biomarkers for aggressive thyroid carcinomas. Proteomics. 2013;13:771–787. doi: 10.1002/pmic.201200356.
    1. Pagni F., L’Imperio V., Bono F., Garancini M., Roversi G., de Sio G., Galli M., Smith A.J., Chinello C., Magni F. Proteome analysis in thyroid pathology. Expert Rev. Proteom. 2015;12:375–390. doi: 10.1586/14789450.2015.1062369.
    1. Galli M., Pagni F., de Sio G., Smith A., Chinello C., Stella M., L’Imperio V., Manzoni M., Garancini M., Massimini D., et al. Proteomic profiles of thyroid tumors by mass spectrometry-imaging on tissue microarrays. Biochim. Biophys. Acta. 2016 doi: 10.1016/j.bbapap.2016.11.020.
    1. Giusti L., Iacconi P., Ciregia F., Giannaccini G., Donatini G.L., Basolo F., Miccoli P., Pinchera A., Lucacchini A. Fine-needle aspiration of thyroid nodules: Proteomic analysis to identify cancer biomarkers. J. Proteome Res. 2008;7:4079–4088. doi: 10.1021/pr8000404.
    1. Giusti L., Iacconi P., Ciregia F., Giannaccini G., Basolo F., Donatini G., Miccoli P., Lucacchini A. Proteomic analysis of human thyroid fine needle aspiration fluid I. J. Endocrinol. Nvestig. 2007;30:865–869. doi: 10.1007/BF03349229.
    1. Ciregia F., Giusti L., Molinaro A., Niccolai F., Agretti P., Rago T., Di Coscio G., Vitti P., Basolo F., Iacconi P., et al. Presence in the pre-surgical fine-needle aspiration of potential thyroid biomarkers previously identified in the post-surgical one. PLoS ONE. 2013;8:e72911. doi: 10.1371/journal.pone.0072911.
    1. Mainini V., Pagni F., Garancini M., Giardini V., de Sio G., Cusi C., Arosio C., Roversi G., Chinello C., Caria P., et al. An alternative approach in endocrine pathology research: MALDI-IMS in papillary thyroid carcinoma. Endocr. Pathol. 2013;24:250–253. doi: 10.1007/s12022-013-9273-8.
    1. Pagni F., Mainini V., Garancini M., Bono F., Vanzati A., Giardini V., Scardilli M., Goffredo P., Smith A.J., Galli M., et al. Proteomics for the diagnosis of thyroid lesions: Preliminary report. Cytopathology. 2015;26:318–324. doi: 10.1111/cyt.12166.
    1. Pagni F., de Sio G., Garancini M., Scardilli M., Chinello C., Smith A.J., Bono F., Leni D., Magni F. Proteomics in thyroid cytopathology: Relevance of MALDI-imaging in distinguishing malignant from benign lesions. Proteomics. 2016;16:1775–1784. doi: 10.1002/pmic.201500448.
    1. Ferris R.L., Baloch Z., Bernet V., Chen A., Fahey T.J., 3rd, Ganly I., Hodak S.P., Kebebew E., Patel K.N., Shaha A., et al. American thyroid association statement on surgical application of molecular profiling for thyroid nodules: Current impact on perioperative decision making. Thyroid. 2015;25:760–768. doi: 10.1089/thy.2014.0502.

Source: PubMed

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