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Performance of a dual-component molecular assay in cytologically indeterminate thyroid nodules

  • Endocrine Genetics/Epigenetics
  • Published:
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Abstract

Purpose

Deciding whether patients with a cytologically indeterminate thyroid nodule should be referred for surgery or for active surveillance is an important challenge for clinicians. The aim of this study was to evaluate the performance of a novel dual-component molecular assay as an ancillary molecular method for resolving indeterminate thyroid nodule cytology.

Methods

We selected 156 thyroid nodules from those that had undergone fine-needle aspiration processed by liquid-based cytology and surgical resection between June 2016 and December 2017. The sample set included 63 nodules cytologically classified as indeterminate, and 93 other nodules randomly selected from those with non-diagnostic, benign, suspicious, or malignant cytology. Nucleic acids from each nodule were subjected to next-generation sequencing analysis for mutation detection in 23 genes and to digital polymerase chain reaction (PCR) evaluation for miR-146b-5p expression levels.

Results

Used alone, mutation analysis in the indeterminate subset (cancer prevalence: 22.5%) displayed high sensitivity (89%) and NPV (96%). In contrast, the miR-146b-5p assay offered high specificity (93%) and PPV (93%). Combined use of both analyses improved panel performance by eliminating false-negative results.

Conclusions

These preliminary data suggest that a dual-component molecular test can increase the diagnostic accuracy of thyroid cytology alone by reducing the number of nodules that will be classified as indeterminate and increasing those that can be reliably classified as benign. If these findings are confirmed, this test can be considered for use in clinical practice and is expected to reduce diagnostic surgery and health care costs, and to improve patient quality of life.

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References

  1. B.R. Haugen, E.K. Alexander, K.C. Bible, G.M. Doherty, S.J. Mandel, Y.E. Nikiforov, F. Pacini, G.W. Randolph, A.M. Sawka, M. Schlumberger, K.G. Schuff, S.I. Sherman, J.A. Sosa, D.L. Steward, R.M. Tuttle, L. Wartofsky, 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 26, 1–133 (2016). https://doi.org/10.1089/thy.2015.0020

    Article  PubMed  PubMed Central  Google Scholar 

  2. C. Durante, G. Grani, L. Lamartina, S. Filetti, S.J. Mandel, D.S. Cooper, The diagnosis and management of thyroid nodules: a review. JAMA 319, 914–924 (2018). https://doi.org/10.1001/jama.2018.0898

    Article  PubMed  Google Scholar 

  3. M. Bongiovanni, A. Spitale, W.C. Faquin, L. Mazzucchelli, Z.W. Baloch, The Bethesda system for reporting thyroid cytopathology: a meta-analysis. Acta Cytol. 56, 333–339 (2012). https://doi.org/10.1159/000339959

    Article  PubMed  Google Scholar 

  4. E.S. Cibas, S.Z. Ali, The 2017 Bethesda system for reporting thyroid cytopathology. J. Am. Soc. Cytopathol. 6, 217–222 (2017). https://doi.org/10.1016/j.jasc.2017.09.002

    Article  PubMed  Google Scholar 

  5. Z.W. Baloch, V.A. LiVolsi, S.L. Asa, J. Rosai, M.J. Merino, G. Randolph, P. Vielh, R.M. DeMay, M.K. Sidawy, W.J. Frable, Diagnostic terminology and morphologic criteria for cytologic diagnosis of thyroid lesions: a synopsis of the national cancer institute thyroid fine-needle aspiration state of the science conference. Diagn. Cytopathol. 36, 425–437 (2008). https://doi.org/10.1002/dc.20830

    Article  PubMed  Google Scholar 

  6. N. Agrawal, R. Akbani, B.A. Aksoy, A. Ally, H. Arachchi, S.L. Asa, J.T. Auman, M. Balasundaram, S. Balu, S.B. Baylin, M. Behera, B. Bernard, R. Beroukhim, J.A. Bishop, A.D. Black, T. Bodenheimer, L. Boice, M.S. Bootwalla, J. Bowen, R. Bowlby, C.A. Bristow, R. Brookens, D. Brooks, R. Bryant, E. Buda, Y.S.N. Butterfield, T. Carling, R. Carlsen, S.L. Carter, S.E. Carty, T.A. Chan, A.Y. Chen, A.D. Cherniack, D. Cheung, L. Chin, J. Cho, A. Chu, E. Chuah, K. Cibulskis, G. Ciriello, A. Clarke, G.L. Clayman, L. Cope, J.A. Copland, K. Covington, L. Danilova, T. Davidsen, J.A. Demchok, D. DiCara, N. Dhalla, R. Dhir, S.S. Dookran, G. Dresdner, J. Eldridge, G. Eley, A.K. El-Naggar, S. Eng, J.A. Fagin, T. Fennell, R.L. Ferris, S. Fisher, S. Frazer, J. Frick, S.B. Gabriel, I. Ganly, J. Gao, L.A. Garraway, J.M. Gastier-Foster, G. Getz, N. Gehlenborg, R. Ghossein, R.A. Gibbs, T.J. Giordano, K. Gomez-Hernandez, J. Grimsby, B. Gross, R. Guin, A. Hadjipanayis, H.A. Harper, D.N. Hayes, D.I. Heiman, J.G. Herman, K.A. Hoadley, M. Hofree, R.A. Holt, A.P. Hoyle, F.W. Huang, M. Huang, C.M. Hutter, T. Ideker, L. Iype, A. Jacobsen, S.R. Jefferys, C.D. Jones, S.J.M. Jones, K. Kasaian, E. Kebebew, F.R. Khuri, J. Kim, R. Kramer, R. Kreisberg, R. Kucherlapati, D.J. Kwiatkowski, M. Ladanyi, P.H. Lai, P.W. Laird, E. Lander, M.S. Lawrence, D. Lee, E. Lee, S. Lee, W. Lee, K.M. Leraas, T.M. Lichtenberg, L. Lichtenstein, P. Lin, S. Ling, J. Liu, W. Liu, Y. Liu, V.A. LiVolsi, Y. Lu, Y. Ma, H.S. Mahadeshwar, M.A. Marra, M. Mayo, D.G. McFadden, S. Meng, M. Meyerson, P.A. Mieczkowski, M. Miller, G. Mills, R.A. Hadjipanayis, L.E. Mose, A.J. Mungall, B.A. Murray, Y.E. Nikiforov, M.S. Noble, A.I. Ojesina, T.K. Owonikoko, B.A. Ozenberger, A. Pantazi, M. Parfenov, P.J. Park, J.S. Parker, E.O. Paull, C.S. Pedamallu, C.M. Perou, J.F. Prins, A. Protopopov, S.S. Ramalingam, N.C. Ramirez, R. Ramirez, B.J. Raphael, W.K. Rathmell, X. Ren, S.M. Reynolds, E. Rheinbay, M.D. Ringel, M. Rivera, J. Roach, A.G. Robertson, M.W. Rosenberg, M. Rosenthal, S. Sadeghi, G. Saksena, C. Sander, N. Santoso, J.E. Schein, N. Schultz, S.E. Schumacher, R.R. Seethala, J. Seidman, Y. Senbabaoglu, S. Seth, S. Sharpe, K.R.M. Shaw, J.P. Shen, R. Shen, S. Sherman, M. Sheth, Y. Shi, I. Shmulevich, G.L. Sica, J.V. Simons, R. Sinha, P. Sipahimalani, R.C. Smallridge, H.J. Sofia, M.G. Soloway, X. Song, C. Sougnez, C. Stewart, P. Stojanov, J.M. Stuart, S.O. Sumer, Y. Sun, B. Tabak, A. Tam, D. Tan, J. Tang, R. Tarnuzzer, B.S. Taylor, N. Thiessen, L. Thorne, V. Thorsson, R.M. Tuttle, C.B. Umbricht, D.J. Van Den Berg, F. Vandin, U. Veluvolu, R.G.W. Verhaak, M. Vinco, D. Voet, V. Walter, Z. Wang, S. Waring, P.M. Weinberger, N. Weinhold, J.N. Weinstein, D.J. Weisenberger, D. Wheeler, M.D. Wilkerson, J. Wilson, M. Williams, D.A. Winer, L. Wise, J. Wu, L. Xi, A.W. Xu, L. Yang, L. Yang, T.I. Zack, M.A. Zeiger, D. Zeng, J.C. Zenklusen, N. Zhao, H. Zhang, J. Zhang, J.(Julia) Zhang, W. Zhang, E. Zmuda, L. Zou, Integrated genomic characterization of papillary thyroid carcinoma. Cell 159, 676–690 (2015). https://doi.org/10.1016/j.cell.2014.09.050

    Article  CAS  Google Scholar 

  7. I. Landa, T. Ibrahimpasic, L. Boucai, R. Sinha, J.A. Knauf, R.H. Shah, S. Dogan, J.C. Ricarte-Filho, G.P. Krishnamoorthy, B. Xu, N. Schultz, M.F. Berger, C. Sander, B.S. Taylor, R. Ghossein, I. Ganly, J.A. Fagin, Genomic and transcriptomic hallmarks of poorly-differentiated and anaplastic thyroid cancers. J. Clin. Invest. 126, 1052–1066 (2016). https://doi.org/10.1172/JCI85271

    Article  PubMed  PubMed Central  Google Scholar 

  8. C. Ferraz, Can current molecular tests help in the diagnosis of indeterminate thyroid nodule FNAB? Arch. Endocrinol. Metab. 62, 576–584 (2018). https://doi.org/10.20945/2359-3997000000081

    Article  PubMed  Google Scholar 

  9. F. Nardi, F. Basolo, A. Crescenzi, G. Fadda, A. Frasoldati, F. Orlandi, L. Palombini, E. Papini, M. Zini, A. Pontecorvi, P. Vitti, Italian consensus for the classification and reporting of thyroid cytology. J. Endocrinol. Invest. 37, 593–599 (2014). https://doi.org/10.1007/s40618-014-0062-0

    Article  PubMed  Google Scholar 

  10. E.S. Cibas, S.Z. Ali, The 2017 Bethesda system for reporting thyroid cytopathology. J. Am. Soc. Cytopathol. 6, 217–222 (2017). https://doi.org/10.1016/j.jasc.2017.09.002

    Article  PubMed  Google Scholar 

  11. M. Sponziello, S. Benvenuti, A. Gentile, V. Pecce, F. Rosignolo, A.R. Virzì, M. Milan, P.M. Comoglio, E. Londin, P. Fortina, A. Barnabei, M. Appetecchia, F. Marandino, D. Russo, S. Filetti, C. Durante, A. Verrienti, Whole exome sequencing identifies a germline MET mutation in two siblings with hereditary wild-type RET medullary thyroid cancer. Hum. Mutat. 39, 371–377 (2018). https://doi.org/10.1002/humu.23378

    Article  CAS  PubMed  Google Scholar 

  12. M. Sponziello, G. Silvestri, A. Verrienti, A. Perna, F. Rosignolo, C. Brunelli, V. Pecce, E.D. Rossi, C.P. Lombardi, C. Durante, S. Filetti, G. Fadda, A novel nonsense EIF1AX mutation identified in a thyroid nodule histologically diagnosed as oncocytic carcinoma. Endocrine 62, 492–495 (2018)

    Article  CAS  PubMed  Google Scholar 

  13. L.M. Mulligan, Exploiting insights on the RET receptor for personalized cancer medicine. Endocr. Relat. Cancer. 25, T189–T200 (2018). https://doi.org/10.1530/ERC-18-0141

  14. Y.E. Nikiforov, Role of molecular markers in thyroid nodule management: then and now. Endocr. Pract. 23, 979–988 (2017). https://doi.org/10.4158/EP171805.RA

  15. F. Rosignolo, L. Memeo, F. Monzani, C. Colarossi, V. Pecce, A. Verrienti, C. Durante, G. Grani, L. Lamartina, S. Forte, D. Martinetti, D. Giuffrida, D. Russo, F. Basolo, S. Filetti, M. Sponziello, MicroRNA-based molecular classification of papillary thyroid carcinoma. Int. J. Oncol. 50, 1767–1777 (2017). https://doi.org/10.3892/ijo.2017.3960

    Article  CAS  PubMed  Google Scholar 

  16. F. Rosignolo, M. Sponziello, L. Giacomelli, D. Russo, V. Pecce, M. Biffoni, R. Bellantone, C.P. Lombardi, L. Lamartina, G. Grani, C. Durante, S. Filetti, A. Verrienti, Identification of Thyroid-Associated Serum microRNA Profiles and Their Potential Use in Thyroid Cancer Follow-Up. J. Endocr. Soc. 1, 3–13 (2017). https://doi.org/10.1210/js.2016-1032

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. M. Celano, F. Rosignolo, V. Maggisano, V. Pecce, M. Iannone, D. Russo, S. Bulotta, MicroRNAs as biomarkers in thyroid carcinoma. Int. J. Genomics 2017, 6496570 (2017). https://doi.org/10.1155/2017/6496570

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. G. Grani, L. Lamartina, V. Ascoli, D. Bosco, F. Nardi, F. D’Ambrosio, A. Rubini, L. Giacomelli, M. Biffoni, S. Filetti, C. Durante, V. Cantisani, Ultrasonography scoring systems can rule out malignancy in cytologically indeterminate thyroid nodules. Endocrine 57, 256–261 (2017). https://doi.org/10.1007/s12020-016-1148-6

    Article  CAS  PubMed  Google Scholar 

  19. P. Valderrabano, M.J. McGettigan, C.A. Lam, L. Khazai, Z.J. Thompson, C.H. Chung, B.A. Centeno, B. McIver, Thyroid nodules with indeterminate cytology: utility of the American Thyroid Association sonographic patterns for cancer risk stratification. Thyroid 28, 1004–1012 (2018). https://doi.org/10.1089/thy.2018.0085

    Article  PubMed  PubMed Central  Google Scholar 

  20. T. Rago, M. Scutari, F. Santini, V. Loiacono, P. Piaggi, G. Di Coscio, F. Basolo, P. Berti, A. Pinchera, P. Vitti, Real-time elastosonography: useful tool for refining the presurgical diagnosis in thyroid nodules with indeterminate or nondiagnostic cytology. J. Clin. Endocrinol. Metab. 95, 5274–5280 (2010). https://doi.org/10.1210/jc.2010-0901

    Article  CAS  PubMed  Google Scholar 

  21. V. Cantisani, E. David, H. Grazhdani, A. Rubini, M. Radzina, C.F. Dietrich, C. Durante, L. Lamartina, G. Grani, A. Valeria, D. Bosco, C. Di Gioia, F.M. Frattaroli, V. D’Andrea, C. De Vito, D. Fresilli, F. D’Ambrosio, L. Giacomelli, C. Catalano, Prospective evaluation of semiquantitative strain ratio and quantitative 2D ultrasound shear wave elastography (SWE) in association with TIRADS classification for thyroid nodule characterization. Ultraschall Med. 40, 495–503 (2019). https://doi.org/10.1055/a-0853-1821

    Article  PubMed  Google Scholar 

  22. F. Ianni, D. Pascucci, R.M. Paragliola, C.A. Rota, G. Perotti, G. Fadda, A. Pontecorvi, S.M. Corsello, Follow-up or surgery for indeterminate thyroid nodules: could the CUT score application be a support for decision making in the preoperative assessment? Thyroid 30, 65–71 (2019). https://doi.org/10.1089/thy.2018.0649

    Article  CAS  PubMed  Google Scholar 

  23. Z.W. Baloch, S. Fleisher, V.A. LiVolsi, P.K. Gupta, Diagnosis of follicular neoplasm: a gray zone in thyroid fine-needle aspiration cytology. Diagn. Cytopathol. 26, 41–44 (2002). https://doi.org/10.1002/dc.10043

    Article  PubMed  Google Scholar 

  24. R. Promberger, J. Ott, F. Kober, M. Karik, M. Freissmuth, M. Hermann, Normal parathyroid hormone levels do not exclude permanent hypoparathyroidism after thyroidectomy. Thyroid 21, 145–150 (2011). https://doi.org/10.1089/thy.2010.0067

    Article  CAS  PubMed  Google Scholar 

  25. E. Kandil, B. Krishnan, S.I. Noureldine, L. Yao, R.P. Tufano, Hemithyroidectomy: a meta-analysis of postoperative need for hormone replacement and complications. ORL 75, 6–17 (2013). https://doi.org/10.1159/000345498

    Article  CAS  PubMed  Google Scholar 

  26. J.A. Sosa, H.M. Bowman, J.M. Tielsch, N.R. Powe, T.A. Gordon, R. Udelsman, The importance of surgeon experience for clinical and economic outcomes from thyroidectomy. Ann. Surg. 228, 320–330 (1998). https://doi.org/10.1097/00000658-199809000-00005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. H. Verloop, M. Louwerens, J.W. Schoones, J. Kievit, J.W.A. Smit, O.M. Dekkers, Risk of hypothyroidism following hemithyroidectomy: systematic review and meta-analysis of prognostic studies. J. Clin. Endocrinol. Metab. 97, 2243–2255 (2012). https://doi.org/10.1210/jc.2012-1063

    Article  CAS  PubMed  Google Scholar 

  28. S. Filetti, P.W. Ladenson, M. Biffoni, M.G. D’Ambrosio, L. Giacomelli, S. Lopatriello, The true cost of thyroid surgery determined by a micro-costing approach. Endocrine 55, 519–529 (2017). https://doi.org/10.1007/s12020-016-0980-z

    Article  CAS  PubMed  Google Scholar 

  29. K.N. Patel, T.E. Angell, J. Babiarz, N.M. Barth, T. Blevins, Q.-Y. Duh, R.A. Ghossein, R.M. Harrell, J. Huang, G.C. Kennedy, S.Y. Kim, R.T. Kloos, V.A. LiVolsi, G.W. Randolph, P.M. Sadow, M.H. Shanik, J.A. Sosa, S.T. Traweek, P.S. Walsh, D. Whitney, M.W. Yeh, P.W. Ladenson, Performance of a genomic sequencing classifier for the preoperative diagnosis of cytologically indeterminate thyroid nodules. JAMA Surg. 153, 817–824 (2018). https://doi.org/10.1001/jamasurg.2018.1153

    Article  PubMed  PubMed Central  Google Scholar 

  30. Y.E. Nikiforov, D.L. Steward, S.E. Carty, R.S. Sippel, S.P. Yang, J.A. Sosa, J.A. Sipos, J.J. Figge, S. Mandel, B.R. Haugen, K.D. Burman, Z.W. Baloch, R.V. Lloyd, R.R. Seethala, W.E. Gooding, S.I. Chiosea, C. Gomes-Lima, R.L. Ferris, J.M. Folek, R.A. Khawaja, P. Kundra, K.S. Loh, C.B. Marshall, S. Mayson, K.L. McCoy, M.E. Nga, K.Y. Ngiam, M.N. Nikiforova, J.L. Poehls, M.D. Ringel, H. Yang, L. Yip, Performance of a multigene genomic classifier in thyroid nodules with indeterminate cytology: a prospective blinded multicenter study. JAMA Oncol. 5, 204–212 (2019). https://doi.org/10.1001/jamaoncol.2018.4616

    Article  PubMed  Google Scholar 

  31. M.N. Nikiforova, S. Mercurio, A.I. Wald, M. Barbi de Moura, K. Callenberg, L. Santana-Santos, W.E. Gooding, L. Yip, R.L. Ferris, Y.E Nikiforov, Analytical performance of the ThyroSeq v3 genomic classifier for cancer diagnosis in thyroid nodules. Cancer 124, 1682–1690 (2018). https://doi.org/10.1002/cncr.31245

    Article  CAS  PubMed  Google Scholar 

  32. E. Labourier, A. Shifrin, A.E. Busseniers, M.A. Lupo, M.L. Manganelli, B. Andruss, D. Wylie, S. Beaudenon-Huibregtse, Molecular testing for miRNA, mRNA, and DNA on fine-needle aspiration improves the preoperative diagnosis of thyroid nodules with indeterminate cytology. J. Clin. Endocrinol. Metab. 100, 2743–2750 (2015). https://doi.org/10.1210/jc.2015-1158

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. A.B. Banizs, J.F. Silverman, The utility of combined mutation analysis and microRNA classification in reclassifying cancer risk of cytologically indeterminate thyroid nodules. Diagn. Cytopathol. 47, 268–274 (2019). https://doi.org/10.1002/dc.24087

    Article  PubMed  Google Scholar 

  34. G. Lithwick-Yanai, N. Dromi, A. Shtabsky, S. Morgenstern, Y. Strenov, M. Feinmesser, V. Kravtsov, M.E. Leon, M. Hajdúch, S.Z. Ali, C.J. VandenBussche, X. Zhang, L. Leider-Trejo, A. Zubkov, S. Vorobyov, M. Kushnir, Y. Goren, S. Tabak, E. Kadosh, H. Benjamin, T. Schnitzer-Perlman, H. Marmor, M. Motin, D. Lebanony, S. Kredo-Russo, H. Mitchell, M. Noller, A. Smith, O. Dattner, K. Ashkenazi, M. Sanden, K.A. Berlin, D. Bar, E. Meiri, Multicentre validation of a microRNA-based assay for diagnosing indeterminate thyroid nodules utilising fine needle aspirate smears. J. Clin. Pathol. 70, 500–507 (2017). https://doi.org/10.1136/jclinpath-2016-204089

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The study was supported by Ministero dell'Istruzione, dell'Università e della Ricerca, Italy (MIUR, investigator grant 2015 project code PRIN 2015HPMLFY to C.D.), the “Sapienza” University of Rome (grant RM11715C7DD0EF56 to S.F. and RP11916B8919C921 to M.S.), Friuli Venezia Giulia (grant POR FESR PREDITT to G.D.).

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  1. These authors contributed equally: Guido Fadda, Sebastiano Filetti

Authors and Affiliations

  1. Department of Translational and Precision Medicine, “Sapienza” University of Rome, 00161, Rome, Italy

    Marialuisa Sponziello, Antonella Verrienti, Giorgio Grani, Valeria Pecce, Luana Abballe, Valeria Ramundo, Cosimo Durante & Sebastiano Filetti

  2. Division of Anatomic Pathology and Histology, Catholic University of Sacred Heart, Foundation “Agostino Gemelli” University Hospital, Rome, Italy

    Chiara Brunelli, Esther Diana Rossi, Patrizia Straccia & Guido Fadda

  3. Department of Medicine, University of Udine, 33100, Udine, Italy

    Giuseppe Damante

  4. Department of Health Sciences, “Magna Graecia” University of Catanzaro, 88100, Catanzaro, Italy

    Diego Russo

  5. Division of Endocrine Surgery, Catholic University of Sacred Heart, Foundation “Agostino Gemelli” University Hospital, Rome, Italy

    Celestino Pio Lombardi

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  1. Marialuisa Sponziello
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Sponziello, M., Brunelli, C., Verrienti, A. et al. Performance of a dual-component molecular assay in cytologically indeterminate thyroid nodules. Endocrine 68, 458–465 (2020). https://doi.org/10.1007/s12020-020-02271-y

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