Update on the cytologic and molecular features of medullary thyroid carcinoma

Advances in Anatomic Pathology

Volumn 21, Issue 1, 2014, Pages 26-35

  Pusztaszeri, Marc P ^a   Bongiovanni, Massimo ^b   Faquin, William C ^c,d  

^a GENEVA UNIVERSITY HOSPITALS   (Switzerland)

^b INSTITUTE OF PATHOLOGY   (Switzerland)

^c MASSACHUSETTS GENERAL HOSPITAL   (United States)

^d HARVARD MEDICAL SCHOOL   (United States)

Author keywords

Calcitonin; Cytology; Fine needle aspiration; Immunocytochemistry; Medullary carcinoma; Molecular; Multiple endocrine neoplasia; Rearranged during transfection; Targeted therapy; Thyroid

Indexed keywords

CALCITONIN; CARCINOEMBRYONIC ANTIGEN; MICRORNA;

CLINICAL FEATURE; CYTODIAGNOSIS; CYTOLOGY; DIFFERENTIAL DIAGNOSIS; FAMILIAL CANCER; FINE NEEDLE ASPIRATION BIOPSY; FOLLICULAR CARCINOMA; HUMAN; IMMUNOCYTOCHEMISTRY; PRIORITY JOURNAL; PROTO ONCOGENE; REVIEW; THYROID MEDULLARY CARCINOMA; UTERINE CERVIX CARCINOMA;

HUMANS; THYROID NEOPLASMS;

EID: 84890521585     PISSN: 10724109     EISSN: 15334031     Source Type: Journal    
DOI: 10.1097/PAP.0000000000000004     Document Type: Review

References (108)

1. Rosai J, Carangiu ML, DeLellis. Atlas of Tumor Pathology: Tumors of the Thyroid Gland. Washington, DC: Armed Forces Institute of Pathology; 1992.
2. DeLellis RA, Lloyd RV, Heitz PU, et al. Pathology and Genetics of Tumours of Endocrine Organs: WHO Classification of Tumours.Vol 8: Lyon: IARC Press; 2004.
3. Kebebew E, Ituarte PH, Siperstein AE, et al. Medullary thyroid carcinoma: clinical characteristics, treatment, prognostic factors, and a comparison of staging systems. Cancer. 2000;88: 1139-1148. (Pubitemid 30127676)
4. Jiménez C, Hu MI, Gagel RF. Management of medullary thyroid carcinoma. Endocrinol Metab Clin North Am. 2008; 37: 481-496. (Pubitemid 351698091)
5. Wells SA Jr, Ontjes DA, Cooper CW, et al. The early diagnosis of medullary carcinoma of the thyroid gland in patients with multiple endocrine neoplasia type II. Ann Surg. 1975;182: 362-368.
6. Kaserer K, Scheuba C, Neuhold N, et al. Sporadic versus familial medullary thyroid microcarcinoma: a histopathologic study of 50 consecutive patients. Am J Surg Pathol. 2001;25: 1245-1251. (Pubitemid 32917117)
7. Waguespack SG, Rich TA, Perrier ND, et al. Management of medullary thyroid carcinoma and MEN2 syndromes in childhood. Nat Rev Endocrinol. 2011;7: 596-607.
8. Zenaty D, Aigrain Y, Peuchmaur M, et al. Medullary thyroid carcinoma identified within the first year of life in children with hereditary multiple endocrine neoplasia type 2A (codon 634) and 2B. Eur J Endocrinol. 2009;160: 807-813.
9. Brandi ML, Gagel RF, Angeli A, et al. Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab. 2001;86: 5658-5671. (Pubitemid 33152604)
10. Sanso GE, Domene HM, Garcia R, et al. Very early detection of RET proto-oncogene mutation is crucial for preventive thyroidectomy in multiple endocrine neoplasia type 2 children: presence of C-cell malignant disease in asymptomatic carriers. Cancer. 2002;94: 323-330. (Pubitemid 34081360)
11. Etit D, Faquin WC, Gaz R, et al. Histopathologic and clinical features of medullary microcarcinoma and C-cell hyperplasia in prophylactic thyroidectomies for medullary carcinoma: a study of 42 cases. Arch Pathol Lab Med. 2008;132: 1767-1773.
12. Yang GC, Fried K, Levine PH. Detection of medullary thyroid microcarcinoma using ultrasound-guided fine needle aspiration cytology. Cytopathology. 2013;24: 92-98.
13. Samaan NA, Schultz PN, Hickey RC. Medullary thyroid carcinoma: prognosis of familial versus sporadic disease and the role of radiotherapy. J Clin Endocrinol Metab. 1988;67: 801-805.
14. Roman S, Lin R, Sosa J. Prognosis of medullary thyroidcarcinoma: demographic, clinical, pathologic predictors of survival in 1252 cases. Cancer. 2006;107: 2134-2142. (Pubitemid 44665646)
15. Söderström N, Telenius-Berg M, Akerman M. Diagnosis of medullary carcinoma of the thyroid by fine needle aspiration biopsy. Acta Med Scand. 1975;197: 71-76.
16. Das DK, Mallik MK, George SS, et al. Secretory activity in medullary thyroid carcinoma: a cytomorphological and immunocytochemical study. Diagn Cytopathol. 2007;35: 329-337. (Pubitemid 46835022)
17. Das A, Gupta SK, Banerjee AK, et al. Atypical cytologic features of medullary carcinoma of the thyroid. A review of 12 cases. Acta Cytol. 1992;36: 137-141.
18. Zeppa P, Vetrani A, Marino M, et al. Fine-needle aspiration cytology of medullary thyroid carcinoma: a review of 18 cases. Cytopathology. 1990;1: 35-44.
19. Mendonca ME, Ramos S, Soares J. Medullary carcinoma of thyroid: a re-evaluation of the cytological criteria of diagnosis. Cytopathology. 1991;2: 93-102.
20. Bose S, Kapila K, Verma K. Medullary carcinoma of the thyroid: a cytological, immuno-cytochemical, and ultrastructural study. Diagn Cytopathol. 1992;8: 28-32.
21. Duskova J, Limanova Z. Cytologic diagnosis of medullary carcinoma of the thyroid gland. Cesk Patol. 1993;29:15-21, (article in Czech).
22. Collins BT, Cramer HM, Tabatowski K, et al. Fine needle aspiration of medullary carcinoma of the thyroid. Cytomorphology, immunocytochemistry and electron microscopy. Acta Cytol. 1995;39: 920-930.
23. Green I, Ali SZ, Allen EA, et al. A spectrum of cytopathologic variations in medullary thyroid carcinoma. Fine needle aspiration findings in 19 cases. . Cancer. 1997;81: 40-44. (Pubitemid 28275326)
24. Us-Krasovec M, Auersperg M, Bergant D, et al. Medullary carcinoma of the thyroid. Pathologica. 1998;90: 5-13.
25. Kumar PV, Hodjati H, Monabati A, et al. Medullary thyroid carcinoma. Rare cytologic findings. Acta Cytol. 2000;44: 181-184. (Pubitemid 30163860)
26. Papaparaskeva K, Nagel H, Droese M. Cytologic diagnosis of medullary carcinoma of the thyroid gland. Diagn Cytopathol. 2000;22: 351-358. (Pubitemid 30396793)
27. Bhanot P, Yang J, Schnadig VJ, et al. Role of FNA cytology and immunochemistry in the diagnosis and management of medullary thyroid carcinoma: report of six cases and review of the literature. Diagn Cytopathol. 2007;35: 285-292. (Pubitemid 46652562)
28. Ljungberg O. Cytologic diagnosis of medullary carcinoma of the thyroid gland with special regard to demonstration of amyloid in smears of fine needle aspirates. Acta Cytol. 1972; 16: 253-255.
29. Jo VY, Renshaw AA, Krane JF. Relative sensitivity of thyroid fine-needle aspiration by tumor type and size. Diagn Cytopathol. 2013;41: 871-875.
30. Dustin SM, Jo VY, Stelow EB, et al. High sensitivity and positive predictive value of fine-needle aspiration for uncommon thyroid malignancies. Diagn Cytopathol. 2012;40: 416-421.
31. Seningen JL, Nassar A, Henry MR. Correlation of thyroid nodule fine-needle aspiration cytology with corresponding histology at Mayo Clinic, 2001-2007: an institutional experience of 1,945 cases. Diagn Cytopathol. 2012;40(suppl 1): E27-E32.
32. Geddie WR, Bedard YC, Strawbridge HT. Medullary carcinoma of the thyroid in fine needle aspiration biopsies. Am J Clin Pathol. 1984;82: 552-558. (Pubitemid 15203675)
33. Ali SZ, Cibas ES. The Bethesda System for Reporting Thyroid Cytopathology: Definitions, Criteria and Explanatory Notes. New York: Springer; 2010.
34. Kini SR, Miller JM, Hamberger JI, et al. Cytopathologic features of medullary carcinoma of the thyroid. Arch Pathol Lab Med. 1984;108: 156-159. (Pubitemid 14181719)
35. Haleem A, Akhtar M, Ali MA, et al. Fine-needle aspiration biopsy of mucus-producing medullary carcinoma of thyroid: report of a case with cytologic, histologic, and ultrastructural correlations. Diagn Cytopathol. 1990;6: 112-117.
36. Schreiner AM, Yang GC. Medullary thyroid carcinoma presenting as rectangular cell type on fine needle aspiration. A diagnostic dilemma. Diagn Cytopathol. 2009;37: 213-216.
37. Forrest CH, Frost FA, de Boer WB, et al. Medullary carcinoma of the thyroid: accuracy of diagnosis by fine needle aspiration cytology. Cancer Cytopathol. 1998;84: 295-302. (Pubitemid 28516867)
38. Clark DP, Faquin WC. Thyroid Cytopathology. New York: Springer; 2005.
39. Pinto A, Nosé V. Localized amyloid in thyroid: are we missing it? Adv Anat Pathol. 2013;20: 61-67.
40. Harach HR, Bergholm U. Small cell variant of medullary carcinoma of the thyroid with neuroblastoma-like features. Histopathology. 1992;21: 378-380.
41. Kumar M, Gupta P, Chaubey A. The thyroid: an extremely rare primary site of neuroblastoma. Hum Pathol. 2006;37: 1357-1360. (Pubitemid 44380284)
42. Yerly S, Triponez F, Meyer P, et al. Medullary thyroid carcinoma, small cell variant, as a diagnostic challenge on fine needle aspiration: a case report. Acta Cytol. 2010;54(suppl 5): 911-917.
43. Beach DF, Klump WJ, Haddad G, et al. Extrapulmonary small cell: a novel case of small cell carcinoma of the thyroid gland. Med Oncol. 2012;29: 1405-1408.
44. Eusebi V, Damiani S, Riva C, et al. Calcitonin free oat-cell carcinoma of the thyroid gland. Virchows Arch A Pathol Anat Histopathol. 1990;417: 267-271. (Pubitemid 20226250)
45. Matias-Guiu X, LaGuette J, Puras-Gil AM, et al. Metastatic neuroendocrine tumors to the thyroid gland mimicking medullary carcinoma: a pathologic and immunohistochemical study of six cases. Am J Surg Pathol. 1997;21: 754-762. (Pubitemid 27406545)
46. Jones TD, Kernek KM, Yang XJ, et al. Thyroid transcription factor 1 expression in small cell carcinoma of the urinary bladder: an immunohistochemical profile of 44 cases. Hum Pathol. 2005;36: 718-723. (Pubitemid 41112025)
47. Agoff SN, Lamps LW, Philip AT, et al. Thyroid transcription factor-1 is expressed in extrapulmonary small cell carcinomas but not in other extrapulmonary neuroendocrine tumors. Mod Pathol. 2000;13: 238-242. (Pubitemid 30207508)
48. Kazaure HS, Roman SA, Sosa JA. Medullary thyroid microcarcinoma: a population-level analysis of 310 patients. Cancer. 2012;118: 620-627.
49. Hanna AN, Michael CW, Jing X. Mixed medullary-follicular carcinoma of the thyroid: diagnostic dilemmas in fine-needle aspiration cytology. Diagn Cytopathol. 2011;39: 862-865.
50. Hsieh MH, Lin MC, Shun CT, et al. Fine needle aspiration cytology of mixed medullary-follicular thyroid carcinoma: a case report. Acta Cytol. 2008;52: 361-365.
51. Suster S. Thyroid tumors with a follicular growth pattern: problems in differential diagnosis. Arch Pathol Lab Med. 2006;130: 984-988. (Pubitemid 44061428)
52. Dominguez-Malagon H, Delgado-Chavez R, Torres-Najera M, et al. Oxyphil and squamous variants of medullary thyroid carcinoma. Cancer. 1989;63: 1183-1188. (Pubitemid 19074752)
53. Dedivitis RA, Di Giovanni JH, Silva GF, et al. Oncocytic variant of medullary thyroid carcinoma: case report. Arq Bras Endocrinol Metabol. 2004;48: 315-317.
54. Kulacoglu S, Ashton-Key M, Buley I. Pitfalls in the diagnosis of papillary carcinoma of the thyroid. Cytopathology. 1998;9: 193-200. (Pubitemid 28277266)
55. Wirth LJ, Ross DS, Randolph GW, et al. Case records of the Massachusetts General Hospital. Case 5-2013. A 52-year-old woman with a mass in the thyroid. N Engl J Med. 2013; 368: 664-673.
56. Adnan Z, Arad E, Dana J, et al. Simultaneous occurrence of medullary and papillary thyroid microcarcinomas: a case series and review of the literature. J Med Case Rep. 2013;7:26.
57. Santosh KV, Raychaudhuri S, Subramanya H, et al. Cytology of hyalinising trabecular adenoma-like variant of medullary thyroid carcinoma. J Cancer Res Ther. 2011;7: 189-191.
58. Bockhorn M, Sheu SY, Frilling A, et al. Paraganglioma-like medullary thyroid carcinoma: a rare entity. Thyroid. 2005;15: 1363-1367. (Pubitemid 43132683)
59. Huss LJ, Mendelsohn G. Medullary carcinoma of the thyroid gland: an encapsulated variant resembling the hyalinizing trabecular (paraganglioma-like) adenoma of thyroid. Mod Pathol. 1990;3: 581-585.
60. Ikeda T, Satoh M, Azuma K, et al. Medullary thyroid carcinoma with a paraganglioma-like pattern and melanin production: a case report with ultrastructural and immunohistochemical studies. Arch Pathol Lab Med. 1998;122: 555-558. (Pubitemid 28262189)
61. Ryska A, Cap J, Vaclavikova E, et al. Paraganglioma-like medullary thyroid carcinoma: fine needle aspiration cytology features with histological correlation. Cytopathology. 2009;20: 188-194.
62. Sneige N, Mackay B, Ordonez NG, et al. Laryngeal paraganglioma. Report of two tumors with immuno-histochemical and ultrastructural analysis. Arch Otolaryngol. 1983;109: 113-117. (Pubitemid 13191836)
63. Matias-Guiu X, Machin P, Pons C, et al. Sustentacular cells occur frequently in the familial form of medullary thyroid carcinoma. J Pathol. 1998;184: 420-423. (Pubitemid 28179902)
64. LaGuette J, Matias-Guiu X, Rosai J. Thyroid paraganglioma: a clinicopathologic and immunohistochemical study of three cases. Am J Surg Pathol. 1997;21: 748-753. (Pubitemid 27406544)
65. Bourtsos EP, Bedrossian CW, De Frias DV, et al. Thyroid plasmacytoma mimicking medullary carcinoma: a potential pitfall in aspiration cytology. Diagn Cytopathol. 2000;23: 354-358.
66. Takami H, Bessho T, Kameya T, et al. Immunohistochemical study of medullary thyroid carcinoma: relationship of clinical features to prognostic factors in 36 patients. World J Surg. 1988;12: 572-579.
67. Hirsch MS, Faquin WC, Krane JF. Thyroid transcription factor-1, but not p53, is helpful in distinguishing moderately differentiated neuroendocrine carcinoma of the larynx from medullary carcinoma of the thyroid. Mod Pathol. 2004;17: 631-636. (Pubitemid 38715484)
68. McCluggage WG, Cameron CH, Arthur K, et al. Atypical carcinoid tumor of the larynx: an immunohistochemical, ultrastructural, and flow cytometric analysis. Ultrastruct Pathol. 1997;21: 431-438. (Pubitemid 27376667)
69. Khurana R, Agarwal A, Bajpai VK, et al. Unraveling the amyloid associated with human medullary thyroid carcinoma. Endocrinology. 2004;145: 5465-5470. (Pubitemid 39564585)
70. Silva OL, Becker KL, Primack A, et al. Ectopic secretion of calcitonin by oat-cell carcinoma. N Engl J Med. 1974;290: 1122-1123.
71. Silva OL, Becker KL, Primack A, et al. Ectopic production of calcitonin. Lancet. 1973;2:317.
72. Whitelaw AGL, Cohen SL. Ectopic production of calcitonin. Lancet. 1973;2:443.
73. Coombes RC, Hillyard C, Greenberg PB, et al. Plasmaimmunoreactive- calcitonin in patients with non-thyroid tumours. Lancet. 1974;1: 1080-1083.
74. Milhaud G, Calmette C, Taboulet J, et al. Hypersecretion of calcitonin in neoplastic conditions. Lancet. 1974;1: 462-463.
75. Fleury A, Fléjou JF, Sauvanet A, et al. Calcitonin-secreting tumors of the pancreas: about six cases. Pancreas. 1998;16: 545-550. (Pubitemid 28217544)
76. Elisei R, Bottici V, Luchetti F, et al. Impact of routine measurement of serum calcitonin on the diagnosis and outcome of medullary thyroid cancer: experience in 10,864 patients with nodular thyroid disorders. J Clin Endocrinol Metab. 2004;89: 163-168. (Pubitemid 38183876)
77. Colombo C, Verga U, Mian C, et al. Comparison of calcium and pentagastrin tests for the diagnosis and follow-up of medullary thyroid cancer. J Clin Endocrinol Metab. 2012;97: 905-913.
78. Trimboli P, Cremonini N, Ceriani L, et al. Calcitonin measurement in aspiration needle washout fluids has higher sensitivity than cytology in detecting medullary thyroid cancer: A retrospective multicentre study. Clin Endocrinol (Oxf). 2013. [Epub ahead of print].
79. Mousa U, Gursoy A, Ozdemir H, et al. Medullary thyroid carcinoma in a patient with Hashimoto's thyroiditis diagnosed by calcitonin washout from a thyroid nodule. Diagn Cytopathol. 2013;41: 644-646.
80. Boi F, Maurelli I, Pinna G, et al. Calcitonin measurement in wash-out fluid from fine needle aspiration of neck masses in patients with primary and metastatic medullary thyroid carcinoma. J Clin Endocrinol Metab. 2007;92: 2115-2118. (Pubitemid 46997108)
81. Lodish MB, Stratakis CA. RET oncogene in MEN2, MEN2B, MTC and other forms of thyroid cancer. Expert Rev Anticancer Ther. 2008;8: 625-632. (Pubitemid 351818356)
82. Myers SM, Eng C, Ponder BA, et al. Characterization of RET proto-oncogene 30 splicing variants and polyadenylation sites: a novel C-terminus for RET. Oncogene. 1995;11: 2039-2045.
83. Moura MM, Cavaco BM, Pinto AE, et al. High prevalence of RAS mutations in RET-negative sporadic medullary thyroid carcinomas. J Clin Endocrinol Metab. 2011;96:E863-E868.
84. Almeida MQ, Hoff AO. Recent advances in the molecular pathogenesis and targeted therapies of medullary thyroid carcinoma. Curr Opin Oncol. 2012;24: 229-234.
85. Agrawal N, Jiao Y, Sausen M, et al. Exomic sequencing of medullary thyroid cancer reveals dominant and mutually exclusive oncogenic mutations in RET and RAS. J Clin Endocrinol Metab. 2013;98:E364-E369.
86. Drosten M, Pützer BM. Mechanisms of disease: cancer targeting and the impact of oncogenic RET for medullary thyroid carcinoma therapy. Nat Clin Pract Oncol. 2006;3: 564-574. (Pubitemid 44781726)
87. Elisei R, Cosci B, Romei C, et al. Prognostic significance of somatic RET oncogene mutations in sporadic medullary thyroid cancer: a 10-year follow-up study. J Clin Endocrinol Metab. 2008;93: 682-687. (Pubitemid 351398539)
88. Fugazzola L, Muzza M, Mian C, et al. RET genotypes in sporadic medullary thyroid cancer: studies in a large Italian series. Clin Endocrinol (Oxf). 2008;69: 418-425.
89. Schulten HJ, Al-Maghrabi J, Al-Ghamdi K, et al. Mutational screening of RET, HRAS, KRAS, NRAS, BRAF, AKT1, and CTNNB1 in medullary thyroid carcinoma. Anticancer Res. 2011;31: 4179-4183.
90. Boichard A, Croux L, Al Ghuzlan A, et al. Somatic RAS mutations occur in a large proportion of sporadic RETnegative medullary thyroid carcinomas and extend to a previously unidentified exon. J Clin Endocrinol Metab. 2012;97:E2031-E2035.
91. Rapa I, Saggiorato E, Giachino D, et al. Mammalian target of rapamycin pathway activation is associated to RET mutation status in medullary thyroid carcinoma. J Clin Endocrinol Metab. 2011;96: 2146-2153.
92. Xing M. BRAF mutation in thyroid cancer. Endocr Relat Cancer. 2005;12: 245-262. (Pubitemid 40896444)
93. Yana I, Nakamura T, Shin E, et al. Inactivation of the p53 gene is not required for tumorigenesis of medullary thyroid carcinoma or pheochromocytoma. Jpn J Cancer Res. 1992;83: 1113-1116. (Pubitemid 23009027)
94. Herfarth KK, Wick MR, Marshall HN, et al. Absence of TP53 alterations in pheochromocytomas and medullary thyroid carcinomas. Genes Chromosomes Cancer. 1997;20: 24-29. (Pubitemid 27377095)
95. Wu G, Mambo E, Guo Z, et al. Uncommon mutation, but common amplifications, of the PIK3CA gene in thyroid tumors. J Clin Endocrinol Metab. 2005;90: 4688-4693. (Pubitemid 41159359)
96. Wells SA Jr, Robinson BG, Gagel RF, et al. Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial. J Clin Oncol. 2012;30: 134-141.
97. Sherman SI. Lessons learned and questions unanswered from use of multitargeted kinase inhibitors in medullary thyroid cancer. Oral Oncol. 2013;49: 707-710.
98. Schoffski P, Elisei R, Muller S, et al. Aninternational, doubleblind, randomized, placebo-controlled phase III trial (EXAM) of cabozantinib (XL184) in medullary thyroid carcinoma (MTC) patients (pts) with documented RECIST progression at baseline. J Clin Oncol. 2012;30:5508.
99. Lam ET, Ringel MD, Kloos RT, et al. Phase II clinical trial of sorafenib in metastatic medullary thyroid cancer. J Clin Oncol. 2011;28: 2323-2330.
100. Ahmed M, Barbachano Y, Riddell A, et al. Analysis of the efficacy and toxicity of sorafenib in thyroid cancer: a phase II study in a UK based population. Eur J Endocrinol. 2011;165: 315-322.
101. Carr LL, Mankoff DA, Goulart BH, et al. Phase II study of daily sunitinib in FDG-PET-positive, iodine-refractory differentiated thyroid cancer and metastatic medullary carcinoma of the thyroid with functional imaging correlation. Clin Cancer Res. 2011;16: 5260-5268.
102. Cohen EE, Rosen LS, Vokes EE, et al. Axitinib is an active treatment for all histologic subtypes of advanced thyroid cancer: results from a phase II study. J Clin Oncol. 2008;26: 4708-4713.
103. Schlumberger MJ, Elisei R, Bastholt L, et al. Phase II study of safety and efficacy of motesanib in patients with progressive or symptomatic, advanced or metastatic medullary thyroid cancer. J Clin Oncol. 2009;27: 3794-3801.
104. Giunti S, Antonelli A, Amorosi A, et al. Cellular signaling pathway alterations and potential targeted therapies for medullary thyroid carcinoma. Int J Endocrinol. 2013;2013: 803171.
105. Hong D, Ye L, Gagel R, et al. Medullary thyroid cancer: targeting the RET kinase pathway with sorafenib/tipifarnib. Mol Cancer Ther. 2008;7: 1001-1006.
106. Mian C, Pennelli G, Fassan M, et al. MicroRNA profiles in familial and sporadic medullary thyroid carcinoma: preliminary relationships with RET status and outcome. Thyroid. 2012;22: 890-896.
107. Abraham D, Jackson N, Gundara JS, et al. MicroRNA profiling of sporadic and hereditary medullary thyroid cancer identifies predictors of nodal metastasis, prognosis, and potential therapeutic targets. Clin Cancer Res. 2011;17: 4772-4781.
108. Nikiforova MN, Tseng GC, Steward D, et al. MicroRNA expression profiling of thyroid tumors: biological significance and diagnostic utility. J Clin Endocrinol Metab. 2008;93: 1600-1608. (Pubitemid 351656494)