Advertisement

Molecular Risk Stratification of Well-Differentiated Thyroid Cancer

  • Todd P. W. McMullen
  • David C. Williams
Part of the Head and Neck Cancer Clinics book series (HNCC)

Abstract

Thyroid nodules are a common problem worldwide. The incidence and aetiology of nodule formation may vary by geography, but a common problem faced by all physicians is how to differentiate benign disease from malignancy. Clinical examination and ultrasonography may identify advanced thyroid carcinoma, but the diagnosis of the vast majority of well-differentiated thyroid cancers (WDTC) relies upon fine-needle aspiration biopsy (FNAB). Important advances in timely identification and management of thyroid cancer have been achieved by improvements in biopsy technique and standardization of thyroid cytopathology reporting. However, many patients still require a thyroid lobectomy before malignancy can be diagnosed. Minimizing the morbidity and cost of diagnostic surgery is an important goal given that the number of patients screened for thyroid malignancy continues to increase significantly across the world. In both the northern and southern hemispheres the incidence of thyroid cancer has more than doubled in the past two decades. Many investigators are now focusing their efforts on improving the diagnostic potential of aspiration biopsies through molecular diagnostics. Success in these efforts is reflected by the appearance of commercially available options for molecular diagnostics in thyroid nodule specimens. In the future, immunocytochemical markers combined with mutation analysis and large-scale genetic sequencing are likely to be used to define distinct benign and malignant signatures in thyroid neoplasms.

Keywords

Thyroid Cancer Thyroid Carcinoma Papillary Thyroid Carcinoma Thyroid Nodule BRAF Mutation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Kent WD, Hall SF, Isotalo PA, et al. Increased incidence of differentiated thyroid carcinoma and detection of subclinical disease. CMAJ. 2007;177:1357–61.PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Li N, Du X, Reitzel L, et al. Impact of enhanced detection on the increase in thyroid cancer incidence in the US: review of incidence trends by socioeconomic status within the surveillance, epidemiology, and end results registry, 1980–2008. Thyroid. 2013;23:103–10.Google Scholar
  3. 3.
    Agate L, Lorusso L, Elisei R. New and old knowledge on differentiated thyroid cancer epidemiology and risk factors. J Endocrinol Invest. 2012;35(6 Suppl):3–9.PubMedGoogle Scholar
  4. 4.
    Ezzat S, Sarti DA, Cain DR, et al. Thyroid incidentalomas. Prevalence by palpation and ultrasonography. Arch Intern Med. 1994;154:1838–40.PubMedCrossRefGoogle Scholar
  5. 5.
    Yuen AP, Ho AC, Wong BY. Ultrasonographic screening for occult thyroid cancer. Head Neck. 2011;33:453–7.PubMedCrossRefGoogle Scholar
  6. 6.
    Gharib H, Goellner JR. Fine-needle aspiration biopsy of the thyroid: an appraisal. Ann Intern Med. 1993;118:282–9.PubMedCrossRefGoogle Scholar
  7. 7.
    Berker D, Aydin Y, Ustun I, et al. The value of fine-needle aspiration biopsy in subcentimeter thyroid nodules. Thyroid. 2008;18:603–8.PubMedCrossRefGoogle Scholar
  8. 8.
    The American Thyroid Association (ATA) guidelines taskforce on thyroid nodules and differentiated thyroid cancer, Cooper DS, Doherty GM, Haugen BR, et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2009;19:1167–214.CrossRefGoogle Scholar
  9. 9.
    Mathur A, Weng J, Moses W, et al. A prospective study evaluating the accuracy of using combined clinical factors and candidate diagnostic markers to refine the accuracy of thyroid fine needle aspiration biopsy. Surgery. 2010;148:1170–6; discussion 1176–7.PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Wang CC, Friedman L, Kennedy GC, et al. A large multicenter correlation study of thyroid nodule cytopathology and histopathology. Thyroid. 2011;21:243–51.PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Lewis CM, Chang KP, Pitman M, et al. Thyroid fine-needle aspiration biopsy: variability in reporting. Thyroid. 2009;19:717–23.PubMedCrossRefGoogle Scholar
  12. 12.
    Layfield LJ, Cibas ES, Baloch Z. Thyroid fine needle aspiration cytology: a review of the National Cancer Institute state of the science symposium. Cytopathology. 2010;21:75–85.PubMedCrossRefGoogle Scholar
  13. 13.
    Bongiovanni M, Spitale A, Faquin WC, et al. The Bethesda system for reporting thyroid cytopathology: a meta-analysis. Acta Cytol. 2012;56:333–9.PubMedCrossRefGoogle Scholar
  14. 14.
    Tee YY, Lowe AJ, Brand CA, et al. Fine-needle aspiration may miss a third of all malignancy in palpable thyroid nodules: a comprehensive literature review. Ann Surg. 2007;246:714–20.PubMedCrossRefGoogle Scholar
  15. 15.
    Roh MH, Jo VY, Stelow EB, et al. The predictive value of the fine-needle aspiration diagnosis ‘suspicious for a follicular neoplasm, hurthle cell type’ in patients with hashimoto thyroiditis. Am J Clin Pathol. 2011;135:139–45.PubMedCrossRefGoogle Scholar
  16. 16.
    Tissell LE. Role of lymphadenectomy in the treatment of differentiated thyroid carcinomas. Br J Surg. 1998;85:1025–6.CrossRefGoogle Scholar
  17. 17.
    Rotstein L. The role of lymphadenectomy in the management of papillary carcinoma of the thyroid. J Surg Oncol. 2009;99:186–8.PubMedCrossRefGoogle Scholar
  18. 18.
    Wada N, Duh QY, Sugino K, et al. Lymph node metastasis from 259 papillary thyroid microcarcinomas: frequency, pattern of occurrence and recurrence, and optimal strategy for neck dissection. Ann Surg. 2003;237:399–407.PubMedCentralPubMedGoogle Scholar
  19. 19.
    Harwood J, Clark OH, Dunphy JE. Significance of lymph node metastasis in differentiated thyroid cancer. Am J Surg. 1978;136:107–12.PubMedCrossRefGoogle Scholar
  20. 20.
    Mazzaferri EL, Young L. Papillary thyroid carcinoma: a 10 year follow-up report of the impact of therapy in 576 patients. Am J Med. 1981;70:511–8.PubMedCrossRefGoogle Scholar
  21. 21.
    Low TH, Delbridge L, Sidhu S, et al. Lymph node status influences follow-up thyroglobulin levels in papillary thyroid cancer. Ann Surg Oncol. 2008;15:2827–32.PubMedCrossRefGoogle Scholar
  22. 22.
    Verburg FA, Mäder U, Tanase K, et al. Life expectancy is reduced in differentiated thyroid cancer patients ≥45 years old with extensive local tumor invasion, lateral lymph node, or distant metastases at diagnosis and normal in all other DTC patients. J Clin Endocrinol Metab. 2013;98:172–80.PubMedCrossRefGoogle Scholar
  23. 23.
    Smith VA, Sessions RB, Lentsch EJ. Cervical lymph node metastasis and papillary thyroid carcinoma: does the compartment involved affect survival? Experience from the SEER database. J Surg Oncol. 2012;106:357–62.PubMedCrossRefGoogle Scholar
  24. 24.
    Lundgren CI, Hall P, Dickman PW, et al. Clinically significant prognostic factors for differentiated thyroid carcinoma: a population-based, nested case–control study. Cancer. 2006;106:524–31.Google Scholar
  25. 25.
    Choi JS, Chung WY, Kwak JY, et al. Staging of papillary thyroid carcinoma with ultrasonography: performance in a large series. Ann Surg Oncol. 2011;18:3572–8.PubMedCrossRefGoogle Scholar
  26. 26.
    Ito Y, Amino N, Miyauchi A. Thyroid ultrasonography. World J Surg. 2010;34:1171–80.PubMedCrossRefGoogle Scholar
  27. 27.
    Sywak M, Cornford L, Roach P, et al. Routine ipsilateral level VI lymphadenectomy reduces postoperative thyroglobulin levels in papillary thyroid cancer. Surgery. 2006;140:1000–5; discussion 1005–7.PubMedCrossRefGoogle Scholar
  28. 28.
    White ML, Doherty GM. Level VI lymph node dissection for papillary thyroid cancer. Minerva Chir. 2007;62:383–93.PubMedGoogle Scholar
  29. 29.
    Sakorafas GH, Sampanis D, Safioleas M. Cervical lymph node dissection in papillary thyroid cancer: current trends, persisting controversies, and unclarified uncertainties. Surg Oncol. 2010;19:e57–70.PubMedCrossRefGoogle Scholar
  30. 30.
    Nikiforov YE. Thyroid carcinoma: molecular pathways and therapeutic targets. Mod Pathol. 2008;21:S37–43.PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    Riesco-Eizaguirrea G, Santisteban P. Molecular biology of thyroid cancer initiation. Clin Transl Oncol. 2007;9:686–93.CrossRefGoogle Scholar
  32. 32.
    Taccaliti A, Boscaro M. Genetic mutations in thyroid carcinoma. Minerva Endocrinol. 2009;34:11–28.PubMedGoogle Scholar
  33. 33.
    Riesco-Eizaguirre G, Santisteban P. New insights in thyroid follicular cell biology and its impact in thyroid cancer therapy. Endocr Relat Cancer. 2007;14:957–77.PubMedCrossRefGoogle Scholar
  34. 34.
    DeLellis RA. Pathology and genetics of thyroid carcinoma. J Surg Oncol. 2006;94:662–9.PubMedCrossRefGoogle Scholar
  35. 35.
    Richardson DS, Gujral TS, Peng S, et al. Transcript level modulates the inherent oncogenicity of RET/PTC oncoproteins. Cancer Res. 2009;69:4861–9.PubMedCrossRefGoogle Scholar
  36. 36.
    Shibru D, Chung KW, Kebebew E. Recent developments in the clinical application of thyroid cancer biomarkers. Curr Opin Oncol. 2008;20:13–8.PubMedCrossRefGoogle Scholar
  37. 37.
    Cassinelli G, Favini E, Degl’Innocenti D, et al. RET/PTC1-driven neoplastic transformation and proinvasive phenotype of human thyrocytes involve met induction and beta-catenin nuclear translocation. Neoplasia. 2009;11:10–21.PubMedCentralPubMedCrossRefGoogle Scholar
  38. 38.
    Greco A, Miranda C, Pierotti MA. Rearrangements of NTRK1 gene in papillary thyroid carcinoma. Mol Cell Endocrinol. 2010;321:44–9.Google Scholar
  39. 39.
    Ciampi R, Nikiforov YE. RET/PTC rearrangements and BRAF mutations in thyroid tumorigenesis. Endocrinology. 2007;148:936–41.PubMedCrossRefGoogle Scholar
  40. 40.
    Buckwalter TL, Venkateswaran A, Lavender M, et al. The roles of phosphotyrosines-294, -404, and -451 in RET/PTC1-induced thyroid tumor formation. Oncogene. 2002;21:8166–72.PubMedCrossRefGoogle Scholar
  41. 41.
    Knauf JA, Kuroda H, Basu S, et al. RET/PTC induced dedifferentiation of thyroid cells is mediated through Y1062 signaling through SHC-RAS-MAP kinase. Oncogene. 2003;22:4406–12.PubMedCrossRefGoogle Scholar
  42. 42.
    Hwang JH, Kim DW, Suh JM, et al. Activation of signal transducer and activator of transcription 3 by oncogenic RET/PTC (rearranged in transformation/papillary thyroid carcinoma) tyrosine kinase: roles in specific gene regulation and cellular transformation. Mol Endocrinol. 2003;17:1155–66.PubMedCrossRefGoogle Scholar
  43. 43.
    Kim YR, Byun HS, Won M, et al. Modulatory role of phospholipase D in the activation of signal transducer and activator of transcription (STAT)-3 by thyroid oncogenic kinase RET/PTC. BMC Cancer. 2008;8:144.PubMedCentralPubMedCrossRefGoogle Scholar
  44. 44.
    Ng YP, Cheung ZH, Ip NY. STAT3 as a downstream mediator of Trk signaling and functions. J Biol Chem. 2006;281:15636–44.PubMedCrossRefGoogle Scholar
  45. 45.
    Powell Jr DJ, Russell J, Nibu K, et al. The RET/PTC3 oncogene: metastatic solid-type papillary carcinomas in murine thyroids. Cancer Res. 1998;58:5523–8.PubMedGoogle Scholar
  46. 46.
    Nikiforova MN, Kimura ET, Gandhi M, 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;88:5399–404.PubMedCrossRefGoogle Scholar
  47. 47.
    Nikiforova MN, Nikiforov YE. Molecular genetics of thyroid cancer: implications for diagnosis, treatment and prognosis. Expert Rev Mol Diagn. 2008;8:83–95.PubMedCrossRefGoogle Scholar
  48. 48.
    Knauf JA, Ma X, Smith EP, et al. Targeted expression of BRAFV600E in thyroid cells of transgenic mice results in papillary thyroid cancers that undergo dedifferentiation. Cancer Res. 2005;65:4238–45.PubMedCrossRefGoogle Scholar
  49. 49.
    Faustino A, Couto JP, Pópulo H, et al. mTOR pathway overactivation in BRAF mutated papillary thyroid carcinoma. Clin Endocrinol Metab. 2012;97:E1139–49.CrossRefGoogle Scholar
  50. 50.
    Xing M. Genetic alterations in the phosphatidylinositol-3 kinase/Akt pathway in thyroid cancer. Thyroid. 2010;20:697–706.PubMedCentralPubMedCrossRefGoogle Scholar
  51. 51.
    Nikiforov YE. Molecular diagnostics of thyroid tumors. Arch Pathol Lab Med. 2011;135:569–77.PubMedGoogle Scholar
  52. 52.
    Vasko V, Espinosa AV, Scouten W, et al. Gene expression and functional evidence of epithelial-to-mesenchymal transition in papillary thyroid carcinoma invasion. Proc Natl Acad Sci USA. 2007;104:2803–8.PubMedCentralPubMedCrossRefGoogle Scholar
  53. 53.
    Knauf JA, Sartor MA, Medvedovic M, et al. Progression of BRAF-induced thyroid cancer is associated with epithelial-mesenchymal transition requiring concomitant MAP kinase and TGFβ signaling. Oncogene. 2011;30:3153–62.PubMedCentralPubMedCrossRefGoogle Scholar
  54. 54.
    Tiwari N, Gheldof A, Tatari M, et al. EMT as the ultimate survival mechanism of cancer cells. Semin Cancer Biol. 2012;22:194–207.PubMedCrossRefGoogle Scholar
  55. 55.
    Mazeh H. MicroRNA as a diagnostic tool in fine-needle aspiration biopsy of thyroid nodules. Oncologist. 2012;17:1032–8.PubMedCentralPubMedCrossRefGoogle Scholar
  56. 56.
    Brait M, Loyo M, Rosenbaum E, et al. Correlation between BRAF mutation and promoter methylation of TIMP3, RARP2 and RASSF1A in thyroid cancer. Epigenetics. 2012;7:710–9.PubMedCentralPubMedCrossRefGoogle Scholar
  57. 57.
    Marotta V, Guerra A, Sapio MR, et al. RET/PTC rearrangement in benign and malignant thyroid diseases: a clinical standpoint. Eur J Endocrinol. 2011;165:499–507.PubMedCrossRefGoogle Scholar
  58. 58.
    Romei C, Elisei R. RET/PTC translocations and clinico-pathological features in human papillary thyroid carcinoma. Front Endocrinol (Lausanne). 2012;3:54.Google Scholar
  59. 59.
    Kim TH, Park YJ, Lim JA, et al. The association of the BRAF (V600E) mutation with prognostic factors and poor clinical outcome in papillary thyroid cancer: a meta-analysis. Cancer. 2012;118:1764–73.PubMedCrossRefGoogle Scholar
  60. 60.
    Tufano RP, Teixeira GV, Bishop J, et al. RAF mutation in papillary thyroid cancer and its value in tailoring initial treatment: a systematic review and meta-analysis. Medicine (Baltimore). 2012;91:274–86.CrossRefGoogle Scholar
  61. 61.
    Basolo F, Torregrossa L, Giannini R, et al. Correlation between the BRAF V600E mutation and tumor invasiveness in papillary thyroid carcinomas smaller than 20 millimeters: analysis of 1060 cases. J Clin Endocrinol Metab. 2010;95:4197–205.PubMedCrossRefGoogle Scholar
  62. 62.
    Rodrigues HG, de Pontes AA, Adan LF. Use of molecular markers in samples obtained from preoperative aspiration of thyroid. Endocr J. 2012;59:417–24.PubMedCrossRefGoogle Scholar
  63. 63.
    Adeniran AJ, Zhu Z, Gandhi M, et al. Correlation between genetic alterations and microscopic features, clinical manifestations, and prognostic characteristics of thyroid papillary carcinomas. Am J Surg Pathol. 2006;30:216–22.PubMedCrossRefGoogle Scholar
  64. 64.
    Motoi N, Sakamoto A, Yamochi T, et al. Role of ras mutation in the progression of thyroid carcinoma of follicular epithelial origin. Pathol Res Pract. 2000;196:1–7.PubMedCrossRefGoogle Scholar
  65. 65.
    Esapa CT, Johnson SJ, Kendall-Taylor P, et al. Prevalence of Ras mutations in thyroid neoplasia. Clin Endocrinol (Oxf). 1999;50:529–35.CrossRefGoogle Scholar
  66. 66.
    Basolo F, Pisaturo F, Pollina LE, et al. N-ras mutation in poorly differentiated thyroid carcinomas: correlation with bone metastases and inverse correlation to thyroglobulin expression. Thyroid. 2000;10:19–23.PubMedCrossRefGoogle Scholar
  67. 67.
    Myers MB, McKim KL, Parsons BL. A subset of papillary thyroid carcinomas contain KRAS mutant subpopulations at levels above normal thyroid. Mol Carcinog. 2014;53:159–67.PubMedCrossRefGoogle Scholar
  68. 68.
    Sahin M, Allard BL, Yates M, et al. PPARgamma staining as a surrogate for PAX8/PPARgamma fusion oncogene expression in follicular neoplasms: clinicopathological correlation and histopathological diagnostic value. J Clin Endocrinol Metab. 2005;90:463–8.PubMedCrossRefGoogle Scholar
  69. 69.
    Mehta V, Nikiforov YE, Ferris RL. Use of molecular biomarkers in FNA specimens to personalize treatment for thyroid surgery. Head Neck. 2013;35:1499–506.PubMedCrossRefGoogle Scholar
  70. 70.
    Ferraz C, Eszlinger M, Paschke R. Current state and future perspective of molecular diagnosis of fine-needle aspiration biopsy of thyroid nodules. J Clin Endocrinol Metab. 2011;96:2016–26.PubMedCrossRefGoogle Scholar
  71. 71.
    Nikiforov YE, Ohori NP, Hodak SP, 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. J Clin Endocrinol Metab. 2011;96:3390–7.PubMedCentralPubMedCrossRefGoogle Scholar
  72. 72.
    Filicori F, Keutgen XM, Buitrago D, et al. Risk stratification of indeterminate thyroid fine-needle aspiration biopsy specimens based on mutation analysis. Surgery. 2011;150:1085–91.PubMedGoogle Scholar
  73. 73.
    Marques AR, Espadinha C, Catarino AL, et al. Expression of PAX8-PPARγ1 rearrangements in both follicular thyroid carcinomas and adenomas. J Clin Endocrinol Metab. 2002;87:3947–52.PubMedGoogle Scholar
  74. 74.
    Moses W, Weng J, Sansano I, et al. Molecular testing for somatic mutations improves the accuracy of thyroid fine-needle aspiration biopsy. World J Surg. 2010;34:2589–94.PubMedCentralPubMedCrossRefGoogle Scholar
  75. 75.
    Cantara S, Capezzone M, Marchisotta S, et al. Impact of proto-oncogene mutation detection in cytological specimens from thyroid nodules improves the diagnostic accuracy of cytology. J Clin Endocrinol Metab. 2010;95:1365–9.PubMedCrossRefGoogle Scholar
  76. 76.
    Griffith OL, Melck A, Jones SJM, et al. Meta-analysis and meta-review of thyroid cancer gene expression profiling studies identifies important diagnostic biomarkers. J Clin Oncol. 2006;24:5043–51.PubMedCrossRefGoogle Scholar
  77. 77.
    Kebebew E, Peng M, Reiff E, et al. ECM1 and TMPRSS4 are diagnostic markers of malignant thyroid neoplasms and improve the accuracy of fine needle aspiration biopsy. Ann Surg. 2005;242:353–61; discussion 361–3.PubMedCentralPubMedGoogle Scholar
  78. 78.
    Kebebew E, Peng M, Reiff E, et al. Diagnostic and prognostic value of cell-cycle regulatory genes in malignant thyroid neoplasms. World J Surg. 2006;30:767–74.PubMedCrossRefGoogle Scholar
  79. 79.
    Rosen J, He M, Umbricht C, et al. A six-gene model for differentiating benign from malignant thyroid tumors on the basis of gene expression. Surgery. 2005;138:1050–6; discussion 1056–7.PubMedCrossRefGoogle Scholar
  80. 80.
    Cerutti JM. Employing genetic markers to improve diagnosis of thyroid tumor fine needle biopsy. Curr Genomics. 2011;12:589–96.PubMedCentralPubMedCrossRefGoogle Scholar
  81. 81.
    Prasad NB, Kowalski J, Tsai HL, et al. Three-gene molecular diagnostic model for thyroid cancer. Thyroid. 2012;22:275–84.PubMedCentralPubMedCrossRefGoogle Scholar
  82. 82.
    Hodak SP, Rosenthal DS, American Thyroid Association Clinical Affairs Committee. Information for clinicians: commercially available molecular diagnosis testing in the evaluation of thyroid nodule FNA specimens. Thyroid. 2013;23:131–4.PubMedCrossRefGoogle Scholar
  83. 83.
    Walsh PS, Wilde JI, Tom EY, et al. Analytical performance verification of a molecular diagnostic for cytology-indeterminate thyroid nodules. J Clin Endocrinol Metab. 2012;97:E2297–306.PubMedCrossRefGoogle Scholar
  84. 84.
    Alexander EK, Kennedy GC, Baloch ZW, et al. Preoperative diagnosis of benign thyroid nodules with indeterminate cytology. N Engl J Med. 2012;367:705–15.PubMedCrossRefGoogle Scholar
  85. 85.
    Chiu CG, Strugnell SS, Griffith OL. Diagnostic utility of galectin-3 in thyroid cancer. Am J Pathol. 2010;176:206–7.CrossRefGoogle Scholar
  86. 86.
    Kouniavsky G, Zeiger MA. The quest for diagnostic molecular markers for thyroid nodules with indeterminate or suspicious cytology. J Surg Oncol. 2012;105:438–43.PubMedCrossRefGoogle Scholar
  87. 87.
    de Matos LL, Del Giglio AB, Matsubayashi CO, et al. Expression of ck-19, galectin-3 and hbme-1 in the differentiation of thyroid lesions: systematic review and diagnostic meta-analysis. Diagn Pathol. 2012;7:97.PubMedCentralPubMedCrossRefGoogle Scholar
  88. 88.
    Carpi A, Naccarato AG, Iervasi G, et al. Large needle aspiration biopsy and galectin-3 determination in selected thyroid nodules with indeterminate FNA-cytology. Br J Cancer. 2006;95:204–9.PubMedCentralPubMedCrossRefGoogle Scholar
  89. 89.
    Leonardi GC, Candido S, Carbone M, et al. MicroRNAs and thyroid cancer: biological and clinical significance (Review). Int J Mol Med. 2012;30:991–9.PubMedGoogle Scholar
  90. 90.
    Kitano M, Rahbari R, Patterson EE, et al. Evaluation of candidate diagnostic microRNAs in thyroid fine-needle aspiration biopsy samples. Thyroid. 2012;22:285–91.PubMedCentralPubMedCrossRefGoogle Scholar
  91. 91.
    Vriens MR, Weng J, Suh I, et al. MicroRNA expression profiling is a potential diagnostic tool for thyroid cancer. Cancer. 2012;118:3426–32.PubMedCrossRefGoogle Scholar
  92. 92.
    de la Chapelle A, Jazdzewski K. MicroRNAs in thyroid cancer. J Clin Endocrinol Metab. 2011;96:3326–36.PubMedCentralPubMedCrossRefGoogle Scholar
  93. 93.
    Keutgen XM, Filicori F, Crowley MJ, et al. A panel of four miRNAs accurately differentiates malignant from benign indeterminate thyroid lesions on fine needle aspiration. Clin Cancer Res. 2012;18:2032–8.PubMedCrossRefGoogle Scholar
  94. 94.
    Mazeh H, Levy Y, Mizrahi I, et al. Differentiating benign from malignant thyroid nodules using micro ribonucleic acid amplification in residual cells obtained by fine needle aspiration biopsy. J Surg Res. 2013;180:216–21.PubMedCrossRefGoogle Scholar
  95. 95.
    Shen R, Liyanarachchi S, Li W, et al. MicroRNA signature in thyroid fine needle aspiration cytology applied to ‘atypia of undetermined significance’ cases. Thyroid. 2012;22:9–16.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© K. Alok Pathak, Richard W. Nason, Janice L. Pasieka, Rehan Kazi, Raghav C. Dwivedi 2015

Authors and Affiliations

  1. 1.Division of Surgical OncologyUniversity of AlbertaEdmontonCanada
  2. 2.Division of General SurgeryUniversity of AlbertaEdmontonCanada

Personalised recommendations