Document Type : Review Article


College of Pharmacy and Medical Sciences, Hebron University, Hebron, Palestine


Thyroid cancer is highly common all around the world. Its prevalence has rapidly increased over the last 30 years in the United States and other developing countries. Fine-needle aspiration biopsy has become the cornerstone of thyroid nodule diagnosis, whose general reliability is outstanding; however, some aspirates have shown undetermined cytological findings that do not provide a definitive malignancy diagnosis. At least 70 molecular and genetic markers in thyroid nodules have been analyzed in an effort to identify molecular markers to differentiate malignant and benign (BN) thyroid nodules. The present review focused on the currently used markers in thyroid cancer diagnosis. A rising number of studies have investigated immunohistochemical markers, such as galectin-3 (GAL3), cytokeratin 19 (CK19), hector battifora mesothelial- 1 (HBME-1), and thyroid peroxidase, along with DNA alterations, including mainly BRAF (B-Raf proto-oncogene, serine/threonine kinase) and RAS (Ras proto-oncogene, GTPase) point mutations, Telomerase reverse transcriptase mutations, ret protooncogene/ papillary thyroid carcinoma and PAX8/PPARG rearrangements, and miRNA signatures and circulating tumor cells for thyroid cancer diagnosis. Although certain markers are promising for differential diagnosis, due to limitations of the substantial prevalence of BN thyroid tumors, none of them is specifically definitive to a large extent. Herein, we also discussed the studies that have supported the use of combinations of several markers, like KIT, TC1, miR-222, and miR-146b combination, as well as GAL3, CK19, and HBME-1 combination, in enhancing the diagnostic accuracy in differentiating malignant and BN tumors.


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Hejaz HA, Abuzaina I, Aldeen RN, Saad S. Currently used and new molecular markers for thyroid cancer diagnosis. Middle East J Cancer. 2022;13(2):193-215. doi: 10.30476/mejc.2022. 87060.1392.

1. Shah JP. Thyroid carcinoma: epidemiology, histology,
and diagnosis. Clin Adv Hematol Oncol. 2015;13(4
Suppl 4):3-6.
2. Nikiforov YE. Radiation-induced thyroid cancer: what
we have learned from chernobyl. Endocr Pathol.
2006;17(4):307-17. doi:10.1007/s12022-006-0001-5.
3. Vaccarella S, Franceschi S, Bray F, Wild CP, Plummer
M, Dal Maso L. Worldwide thyroid-cancer epidemic?
The increasing impact of overdiagnosis. N Engl J
Med. 2016;375(7):614-7. doi:10.1056/NEJMp1604412.
4. Davies L, Ouellette M, Hunter M, Welch HG. The
increasing incidence of small thyroid cancers: where
are the cases coming from? Laryngoscope.
2010;120(12):2446-51. doi:10.1002/lary.21076.
5. Gilliland FD, HuntWC, Morris DM, Key CR.
Prognostic factors for thyroid carcinoma. A populationbased
study of 15,698 cases from the surveillance,
epidemiology, and end results (Seer) program 1973-
1991. Cancer. 1997;79:564-73. doi:10.1002/(sici)1097
6. Liu FC, Lin HT, Lin SF, Kuo CF, Chung TT, Yu HP.
Nationwide cohort study on the epidemiology and
survival outcomes of thyroid cancer. Oncotarget.
2017;8:78429. doi:10.18632/oncotarget.19488.
7. Hsiao SJ, Nikiforov YE. Molecular approaches to
thyroid cancer diagnosis. Endocr Relat Cancer.
2014;21(5):T301-T313. doi:10.1530/ERC-14-0166.
8. Panebianco F, Mazzanti C, Tomei S, Aretini P,
Franceschi S, Lessi F, et al. The combination of four
molecular markers improves thyroid cancer cytologic
diagnosis and patient management. BMC Cancer.
2015;15:918. doi: 10.1186/s12885-015-1917-2.
9. Wei S, Veloski C, Sharda P, Ehya H. Performance of
the afirma genomic sequencing classifier versus gene
expression classifier: An institutional experience.
Cancer Cytopathol. 2019;127:720-4. doi:10.1002/
10. Van Veelen W, De Groot JWB, Acton DS, Hofstra
RMW, Höppener JWM, Links TP, et al. Medullary
thyroid carcinoma and biomarkers: past, present, and
future. J Intern Med. 2009;266:126-40. doi: 10.1111/j.1365-2796.2009.02106.x.
11. Carpi A, Mechanick JI, Saussez S, Nicolini A. Thyroid
tumor marker genomics and proteomics: diagnostic
and clinical implications. J Cell Physiol.
2010;224(3):612-9. jcp.22187.
12. Huang LY, Lee YL, Chou P, Chiu WY, Chu D. Thyroid
fine-needle aspiration biopsy and thyroid cancer
diagnosis: a nationwide population-based study. Plos
One. 2015;10(5):E0127354. doi:10.1371/ journal.pone.
13. Ha EJ, Na DG, Baek JH, Sung JY, Kim JH, Kang,
SY. Us fine-needle aspiration biopsy for thyroid
malignancy: diagnostic performance of seven society
guidelines applied to 2000 thyroid nodules. Radiology.
2018;287(3):893-900. doi: 10.1148/radiol.2018171074.
14. Han LO, Li XY, Cao MM, Cao Y, Zhou LH.
Development and validation of an individualized
diagnostic signature in thyroid cancer. Cancer Med.
2018;7(4):1135-40. doi: 10.1002/cam4.1397.
15. Paschke R, Cantara S, Crescenzi A, Jarzab B, Musholt
TJ, Sobrinho Simoes M. European Thyroid Association
Guidelines regarding thyroid nodule molecular fineneedle
aspiration cytology diagnostics. Eur Thyroid
J. 2017;6(3):115-29. doi: 10.1159/000468519.
16. Singh ON, Iñiguez-Ariza NM, Castro MR. Thyroid
nodules: diagnostic evaluation based on thyroid cancer
risk assessment. BMJ. 2020;7;368:l6670. doi:
17. Feldkamp J, Führer D, Luster M, Musholt TJ, Spitzweg
C, Schott M. Fine needle aspiration in the investigation
of thyroid nodules. Dtsch Arztebl Int. 2016;113:353–
9. doi: 10.3238/arztebl.2016.0353.
18. Choi SH, Han KH, Yoon JH, Moon HJ, Son EJ, Youk
JH, et al. Factors affecting inadequate sampling of
ultrasound-guided fine-needle aspiration biopsy of
thyroid nodules. Clin Endocrinol (Oxf). 2011;74(6):
776-82. doi: 10.1111/j.1365-2265.2011.04011.x.
19. Walker KA. Rate of inadequate sampling in thyroid
fine needle aspiration biopsy. endocrineweb for health
professionals. [Internet] (Accessed date: May 1 2020).
Available at:
20. Boufraqech M, Klubo-Gwiezdzinska J, Kebebew
EMD. MicroRNAs in the thyroid. Best Pract Res Clin
Endocrinol Metab. 2016;30(5):603-19. doi: 10.1016/j.
21. Liu M, Ruan M, Chen L. Update on the molecular
diagnosis and targeted therapy of thyroid cancer. Med
Oncol. 2014;31:973. doi: 10.1007/s12032-014-0973-
22. Vriens MR, Schreinemakers JM, Suh I, Guerrero MA,
Clark OH. Diagnostic markers and prognostic factors
in thyroid cancer. Future Oncol. 2009;5(8):1283-93.
doi: 10.2217/fon.09.85.
23. Géraldine D, Sven S, Fabrice J. Current and future
markers for the diagnosis of thyroid cancer. Clin Oncol
Res. 2019;2(3):3-4. doi: 10.31487/j.COR.2019.03.07.
24. Hsiao SJ, Nikiforov YE. Molecular genetics and
diagnostics of thyroid cancer. Springer International
Publishing AG, part of Springer Nature 2019. Luster
M, et al., editors. The thyroid and its diseases: A
comprehensive guide for the clinician. Thyroid Cancer.
2019;(Part viii):549-562. doi:10.1007/978-3-319-
25. Khatami F, Tavangar S. Review of driver genetic
alterations in thyroid cancers. Iran J Pathol.
26. Yip L. Molecular markers for thyroid cancer diagnosis,
prognosis, and targeted therapy. J Surg Oncol.
2015;111(1):43-50. doi: 10.1002/jso.23768.
27. Cabanillas MED, Mcfadden, DG, Durante, C. Thyroid
cancer. Lancet. 2016;388:2783-95. doi: 10.1016/S0140-
28. Aggarwal N, Swerdlow SH, Kelly LM, Ogilvie JB,
Nikiforova MN, Sathanoori M, et al. Thyroid
carcinoma-associated genetic mutations also occur in
thyroid lymphomas. Mod Pathol. 2012;25(9):1203-
11. doi: 10.1038/modpathol.2012.73.
29. Jin S, Borkhuu O, Bao W, Yang YT. Signaling
pathways in thyroid cancer and their therapeutic
implications. J Clin Med Res. 2016;8(4):284-96. doi:
30. Robbins HL, Hague A. The Pi3k/Akt pathway in
tumors of endocrine tissues. Front Endocrinol
(Lausanne). 2015;6:188. doi: 10.3389/fendo.2015.
31. Leonardi GC, Candido S, Carbone M, Raiti F,
Colaianni V, Garozzo S, et al. BRAF mutations in
papillary thyroid carcinoma and emerging targeted
therapies (review). Mol Med Rep. 2012;6(4):687-94.
doi: 10.3892/mmr.2012.1016.
32. Fagin JA, Wells JSA. Biologic and clinical perspectives
on thyroid cancer. N Engl J Med. 2016;375(11):1054-
67. doi: 10.1056/NEJMra1501993.
33. Cherkaoui GS, Guensi A, Taleb S, Idir MA, Touil N,
Benmoussa R, et al. Poorly differentiated thyroid
carcinoma: a retrospective clinicopathological study.
Pan Afr Med J. 20152;21:137. doi: 10.11604/pamj.
34. Araque KA, Gubbi S, Klubo-Gwiezdzinska J. Updates
on the management of thyroid cancer. Horm Metab
Res. 2020;52(8):562-77. doi:10.1055/a-1089-7870.
35. Pemayun TG. Current diagnosis and management of
thyroid nodules. Acta Med Indones. 2016;48(3):247-
36. Musholt TJ, Fottner C, Weber MM, Eichhorn W,
Pohlenz J, Musholt PB, et al. Detection of papillary
thyroid carcinoma by analysis of Braf and Ret/Ptc1
mutations in fine-needle aspiration biopsies of thyroid
nodules. World J Surg. 2010;34(11):2595-603. doi:
37. Eszlinger M, Paschke R. Molecular fine-needle
aspiration biopsy diagnosis of thyroid nodules by
tumor specific mutations and gene expression patterns.
Mol Cell Endocrinol. 2010;322(1-2):29-37. doi:
38. Marx SJ. Molecular genetics of multiple endocrine
neoplasia types 1 and 2. Nat Rev Cancer. 2005;5:367-
75. doi: 10.1038/nrc1610.
39. Brandi ML, Gagel RF, Angeli A, Bilezikian JP, Beck-
Peccoz P, Bordi C, et al. Guidelines for diagnosis and
therapy of MEN type 1 and type 2. J Clin Endocrinol
Metab. 2001;86(12):5658-71. doi: 10.1210/jcem.86.
40. Traugott A, Moley JF. Medullary thyroid cancer:
medical management and follow-up. Curr Treat
Options Oncol. 2005;6:339-46. doi: 10.1007/s11864-
41. Agrawal N, Jiao Y, Sausen M, Leary R, Bettegowda
C, Roberts NJ, 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(2):E364-9. doi:
42. Eng C, Smith DP, Mulligan LM, Nagai MA, Healey
CS, Ponder MA, et al. Point mutation within the
tyrosine kinase domain of the RET proto-oncogene
in multiple endocrine neoplasia type 2B and related
sporadic tumours. Hum Mol Genet. 1994;3(2):237-
41. doi: 10.1093/hmg/3.2.237. Erratum in: Hum Mol
Genet. 1994;3(4):686.
43. De Groot JWB, Links TP, Plukker JTM, Lips CJM,
Hofstra RMW. Ret as a diagnostic and therapeutic
target in sporadic and hereditary endocrine tumors.
Endocr Rev. 2006;27(5):535-60. doi: 10.1210/er.2006-
44. Subbiah V, Kreitman RJ, Wainberg ZA, Cho JY,
Schellens JHM, Soria JC, et al. Dabrafenib and
Trametinib treatment in patients with locally advanced
or metastatic BRAF V600-mutant anaplastic thyroid
cancer. J Clin Oncol. 2018;36(1):7-13. doi: 10.1200/
45. Smallridge RC, Ain KB, Asa SL, Bible KC, Brierley
JD, Burman KD, et al. American Thyroid Association
guidelines for management of patients with anaplastic
thyroid cancer. Thyroid. 2012;22(11):1104-39. doi:
46. Kane SV, Sharma TP. Cytologic diagnostic approach
to poorly differentiated thyroid carcinoma: a
single?institution study. Cancer Cytopathol.
2015;123(2):82-91. doi: 10.1002/cncy.21500.
47. Juhlin CC. A clinical overview of telomerase-associated
aberrancies in follicular thyroid tumors as diagnostic
and prognostic markers: Tert alert. Scand J Surg.
2020;109(3):187-92. doi: 10.1177/1457496919850434.
48. Penna GC, Vaisman F, Vaisman M, Sobrinho-Simoes
M, Soares P. Molecular markers involved in
tumorigenesis of thyroid carcinoma: focus on
aggressive histotypes. Cytogenet Genome Res. 2016;
150:194-207. doi: 10.1159/000456576.
49. Liu R, Xing M. Diagnostic, and prognostic tert
promoter mutations in thyroid fine-needle aspiration
biopsy. Endocr Relat Cancer. 2014;21(5):825-30. doi:
50. Liu R, Xing M. Tert promoter mutations in thyroid
cancer. Endocr Relat Cancer. 2016;23(3):R143-R155.
doi: 10.1530/ERC-15-0533.
51. Borowczyk M, Szczepanek-Parulska E, Olejarz M,
Więckowska B, Verburg FA, Dębicki S, et al.
Evaluation of 167 gene expression classifier (GEC)
and ThyroSeq v2 diagnostic accuracy in the
preoperative assessment of indeterminate thyroid
nodules: Bivariate/HROC meta-analysis. Endocr
Pathol. 2019;30(1):8-15. doi: 10.1007/s12022-018-
52. Haugen BR. 2015 American thyroid association
management guidelines for adult patients with thyroid
nodules and differentiated thyroid cancer: What is
new and what has changed? Cancer. 2017;123(3):372-
81. doi: 10.1002/cncr.30360.
53. Sahli ZT, Smith PW, Umbricht CB, Zeiger MA.
preoperative molecular markers in thyroid nodules.
Front Endocrinol (Lausanne). 2018;9:179. doi:
54. San Martin VT, Lawrence L, Bena J, Madhun NZ,
Berber E, Elsheikh TM, et al. Real-world comparison
of afirma gec and gsc for the assessment of
cytologically indeterminate thyroid nodules. J Clin
Endocrinol Metab. 2020;105(9):dgaa322. doi:
55. Taye A, Gurciullo D, Miles BA, Gupta A, Owen RP,
Inabnet 3rd WB, et al. Clinical performance of a nextgeneration
sequencing assay (Thyroseq V2) in the
evaluation of indeterminate thyroid nodules. Surgery.
2108;163(1):97-103. doi: 10.1016/j.surg.2017.07.032.
56. Nikiforov YE, Carty SE, Chiosea SI, Coyne C, Duvvuri
U, Ferris RL, 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(23):3627-34. doi: 10.1002/cncr.29038.
57. Valderrabano P, Khazai L, Leon ME, Thompson ZJ,
Ma Z, Chung CH, et al. Evaluation of ThyroSeq v2
performance in thyroid nodules with indeterminate
cytology. Endocr Relat Cancer. 2017;24(3):127-36.
doi: 10.1530/ERC-16-0512.
58. Nikiforova MN, Mercurio S, Wald AI, Barbi de Moura
M, Callenberg K, et al. Analytical performance of the
ThyroSeq v3 genomic classifier for cancer diagnosis
in thyroid nodules. Cancer. 2018;124(8):1682-90. doi:
59. Ohori NP, Landau MS, Carty SE, Yip L, LeBeau SO,
Manroa P, et al. Benign call rate and molecular test result distribution of ThyroSeq v3. Cancer Cytopathol.
2019;127(3):161-8. doi: 10.1002/cncy.22088.
60. Pishkari S, Paryan M, Hashemi M, Baldini E,
Mohammadi-Yeganeh S. The role of microRNAs in
different types of thyroid carcinoma: A comprehensive
analysis to find new miRNA supplementary therapies.
J Endocrinol Invest. 2018;41(3):269-83. doi:
61. Castagna MG, Marzocchi C, Pilli T, Forleo R, Pacini
F, Cantara S. MicroRNA expression profile of thyroid
nodules in fine-needle aspiration cytology: A
confirmatory series. J Endocrinol Invest. 2019;42(1):
97-100. doi: 10.1007/s40618-018-0880-6.
62. Abdullah MI, Junit SM, Ng KL, Jayapalan JJ,
Karikalan B, Hashim OH. Papillary thyroid cancer:
Genetic alterations and molecular biomarker
investigations. Int J Med Sci. 2019;16(3):450-60.
63. Jing W, Li X, Peng R, LvS, Zhang Y, Cao Z, et al.
The diagnostic and prognostic significance of long
noncoding RNAs expression in thyroid cancer: A
systematic review and meta-analysis. Pathol Res Pract.
2018;214(3):327-34. doi: 10.1016/j.prp. 2018.01.008.
64. Chou CK, Chen RF, Chou FF, Chang HW, Chen YJ,
Lee YF, et al. miR-146b is highly expressed in adult
papillary thyroid carcinomas with high risk features
including extrathyroidal invasion and the
BRAF(V600E) mutation. Thyroid. 2010;20(5):489-
94. doi: 10.1089/thy.2009.0027.
65. Bommarito A, Richiusa P, Carissimi E, Pizzolanti G,
Rodolico V, Zito G, et al. BRAFV600E mutation,
TIMP-1 upregulation, and NF-κB activation: closing
the loop on the papillary thyroid cancer trilogy. Endocr
Relat Cancer. 2011;18(6):669-85. doi: 10.1530/ERC-
66. Pacifico F, Leonardi A. Role of Nf-KappaB in thyroid
cancer. Mol Cell Endocrinol. 2010;321(1):29-35. doi:
67. Simon D, Körber C, Krausch M, Segering J, Groth P,
Görges R, et al. Clinical impact of retinoids in redifferentiation
therapy of advanced thyroid cancer: final results
of a pilot study. Eur J Nucl Med Mol Imaging.
2002;29(6):775-82. doi: 10.1007/s00259-001-0737-6.
68. Schwertheim S, Sheu SY, Worm K, Grabellus F,
Schmid KW. Analysis of deregulated miRNAs is
helpful to distinguish poorly differentiated thyroid
carcinoma from papillary thyroid carcinoma. Horm
Metab Res. 2009;41(6):475-81. doi: 10.1055/s-0029-
69. Li D, Jian W, Wei C, Song H, Gu Y, Luo Y, et al.
Down-regulation of miR-181b promotes apoptosis by
targeting Cyld in thyroid papillary cancer. Int J Clin
Exp Pathol. 2014;7 (11):7672-80.
70. Pallante P, Visone R, Ferracin M, Ferraro A, Berlingieri
MT, Troncone G, et al. MicroRNA deregulation in
human thyroid papillary carcinomas. Endocr Relat
Cancer. 2006;13(2):497-508. doi: 10.1677/erc.1.01209.
71. Cancer Genome Atlas Research Network. Integrated
genomic characterization of papillary thyroid
carcinoma. Cell. 2014;159(3):676-90. doi: 10.1016/j.
72. Nikiforova MN, Lynch RA, Biddinger PW, Alexander
EK, Dorn GW 2nd, Tallini G, et al. RAS point mutations
and PAX8-PPAR gamma rearrangement in thyroid
tumors: evidence for distinct molecular pathways in
thyroid follicular carcinoma. J Clin Endocrinol Metab.
2003;88(5):2318-26. doi: 10.1210/jc.2002-021907.
73. Nikiforov YE. Thyroid carcinoma: molecular pathways
and therapeutic targets. Mod Pathol. 2008;21,(Suppl
2):S37-43. doi: 10.1038/modpathol.2008.10.
74. Sun D, Han S, Liu C, Zhou R, Sun W, Zhang Z, et al.
Microrna-199a-5p Functions as a tumor suppressor
via suppressing connective tissue growth factor (CTGF)
in follicular thyroid carcinoma. Med Sci Monit.
2016;22:1210-7. doi: 10.12659/msm.895788.
75. Wojtas B, Ferraz C, Stokowy T, Hauptmann S, Lange
D, Dralle H, et al. Differential miRNA expression
defines migration and reduced apoptosis in follicular
thyroid carcinomas. Mol Cell Endocrinol. 2014;388(1-
2):1-9. doi: 10.1016/j.mce.2014.02.011.
76. Ain KB. Anaplastic thyroid carcinoma: behavior,
biology, and therapeutic approaches. Thyroid.
1998;8(8):715-26. doi:10.1089/thy.1998.8.715.
77. Keutgen XM, Sadowski SM, Kebebew E. Management
of anaplastic thyroid cancer. Gland Surg. 2015;4(1):44-
51. doi: 10.3978/j.issn.2227-684X.2014.12.02.
78. Chang CJ, Chao CH, Xia W, Yang JY, Xiong Y, Li
CW, et al. p53 regulates epithelial-mesenchymal
transition and stem cell properties through modulating
miRNAs. Nat Cell Biol. 2011;13(3):317-23. doi:
10.1038/ncb2173. Erratum in: Nat Cell Biol. 2011;
13(12):1466. Erratum in: Nat Cell Biol. 2011;13(12):
79. Braun J, Hoang-Vu C, Dralle H, Huttelmaier S.
Oncogene. 2010;29(29):4237-44. doi: c10.1038/onc.
80. Fuziwara CS, Kimura ET. MicroRNA deregulation
in anaplastic thyroid cancer biology. Int J Endocrinol.
2014;743450. doi: 10.1155/2014/743450.
81. Duan L, Hao X, Liu Z, Zhang Y, Zhang, G. MiR-129-
5p is down-regulated and involved in the growth,
apoptosis, and migration of medullary thyroid
carcinoma cells through targeting Ret. Febs Lett.
2014;588(9):1644-51. doi: 10.1016/j.febslet.2014.
82. Hofstra RM, Landsvater RM, Ceccherini I, Stulp RP,
Stelwagen T, Luo Y, et al. A mutation in the RET
proto-oncogene associated with multiple endocrine
neoplasia type 2B and sporadic medullary thyroid
carcinoma. Nature. 1994;367(6461):375-6. doi: 10.
83. Lawrie CH, Gal S, Dunlop HM, Pushkaran B, Liggins AP, Pulford K, 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(5):672-5. doi: 10.1111/j.1365-2141.2008.
84. Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman
SK, Pogosova-Agadjanyan EL, et al. Circulating
microRNAs as stable blood-based markers for cancer
detection. Proc Natl Acad Sci U S A. 2008;105(30):
10513-8. doi: 10.1073/pnas.0804549105.
85. Kosaka N, Iguchi H, Ochiya T. Circulating microRNA
in body fluid: a new potential biomarker for cancer
diagnosis and prognosis. Cancer Sci. 2010;101(10):
2087-92. doi: 10.1111/j.1349-7006.2010.01650.x.
86. Lee JC, Zhao JT, Clifton-Bligh RJ, Gill A, Gundara
JS, Ip JC, et al. MicroRNA-222 and microRNA-146b
are tissue and circulating biomarkers of recurrent
papillary thyroid cancer. Cancer. 2013;119(24):4358-
65. doi: 10.1002/cncr.28254.
87. Lee YS, Lim YS, Lee JC, Wang SG, Park HY, Kim
SY, et al. Differential expression levels of plasmaderived
miR-146b and miR-155 in papillary thyroid
cancer. Oral Oncol. 2015;51(1):77-83. doi: 10.1016/j.
88. Li M, Song Q, Li H, Lou Y, Wang L. Correction:
circulating miR-25-3p and miR-451a may be potential
biomarkers for the diagnosis of papillary thyroid
carcinoma. PLoS One. 2015;10(8):E0135549. doi:
89. Gómez Sáez JM. Diagnostic usefulness of tumor
markers in the thyroid cytological samples extracted
by fine-needle aspiration biopsy. Endocr Metab
Immune Disord Drug Targets. 2010;10(1):47-56. doi:
90. Murugan AK, Munirajan AK, Alzahrani AS. Long
noncoding RNAs: emerging players in thyroid cancer
pathogenesis. Endocr Relat Cancer. 2018;25(2):R59-
R82. doi:10.1530/ERC-17-0188.
91. Tano K, Akimitsu N. Long non-coding RNAs in cancer
progression. Front Genet. 2012;3:219. doi: 10.3389/
92. Wang X, Lu X, Geng Z, Yang G, Shi Y. LncRNA
Ptcsc3/miR-574-5p governs cell proliferation and
migration of papillary thyroid carcinoma via
Wnt/βcatenin signaling. J Cell Biochem. 2017;118(12):
4745-52. doi: 10.1002/jcb.26142.
93. Zhang R, Hardin H, Huang W, Chen J, Asioli S, Righi
A, et al. Lloyd RV. Malat1 long non-coding RNA
expression in thyroid tissues: analysis by in situ
hybridization and real-time Pcr. Endocr Pathol.
2017;28(1):7-12. doi: 10.1007/s12022-016-9453-4.
94. Chakravarty D, Sboner A, Nair SS, Giannopoulou E,
Li R, Hennig S, et al. The oestrogen receptor alpharegulated
lncRNA NEAT1 is a critical modulator of
prostate cancer. Nat Commun. 2014;5:5383. doi:
95. Kim YK, Ha HH, Lee JS, Bi X, Ahn YH, Hajar S, et
al. Control of muscle differentiation by a mitochondriatargeted
fluorophore. J Am Chem Soc. 2010;132(2):
576-9. doi: 10.1021/ja906862g.
96. Zeng C, Xu Y, Xu L, Yu X, Cheng J, Yang L, et al.
Inhibition of long non-coding RNA Neat1 impairs
myeloid differentiation in acute promyelocytic
leukemia cells. BMC Cancer. 2014;14:693. doi:
97. Li JH, Zhang SQ, Qiu XG, Zhang SJ, Zheng SH,
Zhang DH. Long non-coding RNA Neat1 promotes
malignant progression of thyroid carcinoma by
regulating miRNA-214. Int J Oncol. 2017;50:708-16.
doi: 10.3892/ijo.2016.3803.
98. Jeong S, Lee J, Kim D, Seol MY, Lee WK, Jeong JJ,
et al. Relationship of focally amplified long noncoding
on chromosome 1 (Fal1) lncRNA with E2f transcription
factors in thyroid cancer. Medicine. 2016;95(4):e2592.
doi: 10.1097/MD.0000000000002592.
99. Wang C, Yan G, Zhang Y, Jia X, Bu P. Long noncoding
RNA Meg3 suppresses migration and invasion
of thyroid carcinoma by targeting of Rac1. Neoplasma.
2015;62(4):541-9. doi: 10.4149/neo_2015_065.
100. Jendrzejewski J, Thomas A, Liyanarachchi S, Eiterman
A, Tomsic J, He H, et al. Ptcsc3 is involved in papillary
thyroid carcinoma development by modulating
S100A4 gene expression. J Clin Endocrinol Metab.
2015;100(10):E1370-E1377. doi: 10.1210/jc. 2015-
101. Barroeta JE, Baloch ZW, Lal P, Pasha TL, Zhang PJ,
Livolsi VA. Diagnostic value of differential expression
of Ck19, galectin-3, Hbme-1, Erk, Ret, and p16 in
benign and malignant follicular-derived lesions of
the thyroid: an immunohistochemical tissue microarray
analysis. Endocr Pathol. 2006;17(3):225-34. doi:
102. De Matos PS, Ferreira AP, De Oliveira Facuri F,
Assumpção LVM, Metze K, Ward LS. Usefulness of
Hbme-1, cytokeratin 19 and galectin-3
immunostaining in the diagnosis of thyroid
malignancy. Histopathology. 2005;47(4):391-401.
doi: 10.1111/j.1365-2559.2005.02221.x.
103. Beesley MF, Mclaren KM. Cytokeratin 19 and
galectin-3 immunohistochemistry in the differential
diagnosis of solitary thyroid nodules. Histopathology.
2002;41(3):236-43. doi: 10.1046/j.1365-2559.2002.
104. Liu Z, Li X, Shi L, Maimaiti Y, Chen T, Li Z, et al.
Cytokeratin 19, thyroperoxidase, Hbme-1 and galectin-
3 in evaluation of aggressive behavior of papillary
thyroid carcinoma. Int J Clin Exp Med. 2014;7(8):
105. De Micco C, Savchenko V, Giorgi R, Sebag F, Henry
JF. Utility of malignancy markers in fine-needle
aspiration cytology of thyroid nodules: comparison
of hector battifora mesothelial antigen-1, thyroid peroxidase, and dipeptidyl aminopeptidase IV. Br J
Cancer. 2008;98(4):818-23. doi: 10.1038/sj.bjc.
106. Weber KB, Shroyer KR, Heinz DE, Nawaz S, Said
MS, Haugen BR. The use of a combination of galectin-
3 and thyroid peroxidase for the diagnosis and
prognosis of thyroid cancer. Am J Clin Pathol.
2004;122(4):524-31. doi: 10.1309/UUQTE505PTN5Q
107. De Micco C, Vassko V, Henry JF. The value of thyroid
peroxidase immunohistochemistry for preoperative
fine-needle aspiration diagnosis of the follicular
variant of papillary thyroid cancer. Surgery.
1999;126(6):1200-4. doi: 10.1067/msy.2099.101428.
108. De Matos LL, Del Giglio AB, Matsubayashi CO, De
Lima Farah M, Del Giglio A, Da Silva Pinhal MA.
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. doi: 10.1186/1746-1596-7-97.
109. Dunderovic D, Lipkovski JM, Boricic I, Soldatovic
I, Bozic V, Cvejic D, et al. Defining the value of
Cd56, Ck19, galectin 3 and Hbme-1 in diagnosis of
follicular cell derived lesions of thyroid with
systematic review of literature. Diagn Pathol.
2015;10:196. doi: 10.1186/s13000-015-0428-4.
110. Arcolia V, Journe F, Renaud F, Leteurtre E, Gabius
HJ, Remmelink M, et al. Combination of galectin-3,
Ck19, and Hbme-1 immunostaining improves the
diagnosis of thyroid cancer. Oncol Lett. 2017;14(4):
4183-9. doi: 10.3892/ol.2017.6719.
111. Rusinek D, Chmielik E, Krajewska J, Jarzab M,
Oczko-Wojciechowska M, Czarniecka A, et al. Current
advances in thyroid cancer management. Are we
ready for the epidemic rise of diagnoses? Int J Mol
Sci. 2017;18(8):1817. doi: 10.3390/ijms18081817.
112. Zargari N, Mokhtari M. Evaluation of diagnostic
utility of immunohistochemistry markers of Trop-2
and Hbme-1 in the diagnosis of thyroid carcinoma.
Eur Thyroid J. 2019;8:1-6.
113. Bhatia P, Deniwar A, Friedlander P, Aslam R, Kandil
E. Diagnostic potential of ancillary molecular testing
in differentiation of benign and malignant thyroid
nodules. Anticancer Res. 2015;35(3):1237-41.
114. Filie AC, Asa SL, Geisinger KR, Logani S, Merino
M, Nikiforov YE, et al. Utilization of ancillary studies
in thyroid fine needle aspirates: a synopsis of the
National Cancer Institute Thyroid Fine Needle
Aspiration State of the Science Conference. Diagn
Cytopathol. 2008;36(6):438-41. doi: 10.1002/dc.
115. Lorch JH. ASCO 2019 — what’s new in thyroid
oncology? Clin Thyroidol. 2019;31(7):269-71. doi:
116. Pusztaszeri MP; Sadow PM, Faquin WC. CD117: A
novel ancillary marker for papillary thyroid carcinoma
in fine-needle aspiration biopsies. Cancer Cytopathol.
2104;122(8). doi: 10.1002/cncy.21437.