Skip to main content
SpringerLink
Log in

Diagnostic and Prognostic Molecular Markers in Thyroid Cancer

  • Chapter
  • First Online:
Thyroid Cancer

Abstract

Thyroid nodules are extremely common, which is accompanied with a rapidly rising incidence of diagnosed thyroid cancer in recent years. The main challenges currently encountered in the clinical management of thyroid nodule and thyroid cancer are the often indeterminate cytology on thyroid fine needle aspiration biopsy in the former case, which creates problematic diagnostic dilemmas, and the often prognostic uncertainty in the latter case, which causes much controversy in managing the risk-harm balance of treatment of thyroid cancer. Molecular markers have emerged to be highly promising in tackling these challenges. Considerable progress has occurred in recent years in the identification and development of diagnostic and prognostic molecular markers for thyroid nodule and thyroid cancer. Many such markers have been investigated and several of them are proven to be clinically useful and are increasingly used as adjunct diagnostic molecular tests with thyroid biopsy. The most prominent examples include the gene expression classifier, genetic panel of BRAF mutation, RAS mutations, RET-PTC and PAX8-PPARĪ³, and the protein marker galectin-3. The best characterized prognostic molecular maker is BRAF V600E mutation, which has been proven to be useful in assisting the risk stratification of PTC; this will now be further enhanced by the recently discovered TERT promoter mutations in thyroid cancer. Several other molecular markers, such as the peripheral blood-based DNA methylation markers and thyroid-stimulating hormone receptor mRNA, also hold promises as diagnostic and prognostic molecular markers for thyroid cancer. It is expected that further optimization and appropriate selection and application of the current and new molecular markers will significantly improve the management of thyroid nodule and thyroid cancer in various clinical settings.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Agretti P, Ferrarini E, Rago T, Candelieri A, De Marco G, Dimida A, Niccolai F, Molinaro A, Di Coscio G, Pinchera A, Vitti P, Tonacchera M. MicroRNA expression profile helps to distinguish benign nodules from papillary thyroid carcinomas starting from cells of fine-needle aspiration. Eur J Endocrinol. 2012;167:393ā€“400.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  2. Alexander EK, Kennedy GC, Baloch ZW, Cibas ES, Chudova D, Diggans J, Friedman L, Kloos RT, LiVolsi VA, Mandel SJ, Raab SS, Rosai J, Steward DL, Walsh PS, Wilde JI, Zeiger MA, Lanman RB, Haugen BR. Preoperative diagnosis of benign thyroid nodules with indeterminate cytology. N Engl J Med. 2012;367:705ā€“15.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  3. Baloch ZW, LiVolsi VA, Asa SL, Rosai J, Merino MJ, Randolph G, Vielh P, DeMay RM, Sidawy MK, Frable WJ. 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. 2008;36:425ā€“37.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  4. Bartolazzi A, Bellotti C, Sciacchitano S. Methodology and technical requirements of the galectin-3 test for the preoperative characterization of thyroid nodules. Appl Immunohistochem Mol Morphol. 2012;20:2ā€“7.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  5. Bartolazzi A, Orlandi F, Saggiorato E, Volante M, Arecco F, Rossetto R, Palestini N, Ghigo E, Papotti M, Bussolati G, Martegani MP, Pantellini F, Carpi A, Giovagnoli MR, Monti S, Toscano V, Sciacchitano S, Pennelli GM, Mian C, Pelizzo MR, Rugge M, Troncone G, Palombini L, Chiappetta G, Botti G, Vecchione A, Bellocco R, Italian Thyroid Cancer Study Group (ITCSG). Galectin-3-expression analysis in the surgical selection of follicular thyroid nodules with indeterminate fine-needle aspiration cytology: a prospective multicentre study. Lancet Oncol. 2008;9:543ā€“9.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  6. Blasco MA. Telomeres and human disease: ageing, cancer and beyond. Nat Rev Genet. 2005;6:611ā€“22.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  7. Cappola AR, Mandel SJ. Molecular testing in thyroid cancer: BRAF mutation status and mortality. JAMA. 2013;309:1529ā€“30.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  8. Cheung CC, Carydis B, Ezzat S, Bedard YC, Asa SL. Analysis of ret/PTC gene rearrangements refines the fine needle aspiration diagnosis of thyroid cancer. J Clin Endocrinol Metab. 2001;86:2187ā€“90.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  9. Chia SY, Milas M, Reddy SK, Siperstein A, Skugor M, Brainard J, Gupta MK. Thyroid-stimulating hormone receptor messenger ribonucleic acid measurement in blood as a marker for circulating thyroid cancer cells and its role in the preoperative diagnosis of thyroid cancer. J Clin Endocrinol Metab. 2007;92:468ā€“75.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  10. Chiu CG, Strugnell SS, Griffith OL, Jones SJ, Gown AM, Walker B, Nabi IR, Wiseman SM. Diagnostic utility of galectin-3 in thyroid cancer. Am J Pathol. 2010;176:2067ā€“81.

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  11. Cohen Y, Xing M, Mambo E, Guo Z, Wu G, Trink B, Beller U, Westra WH, Ladenson PW, Sidransky D. BRAF mutation in papillary thyroid carcinoma. J Natl Cancer Inst. 2003;95:625ā€“7.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  12. Cohen Y, Rosenbaum E, Clark DP, Zeiger MA, Umbricht CB, Tufano RP, Sidransky D, Westra WH. Mutational analysis of BRAF in fine needle aspiration biopsies of the thyroid: a potential application for the preoperative assessment of thyroid nodules. Clin Cancer Res. 2004;10:2761ā€“5.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  13. Coli A, Bigotti G, Zucchetti F, Negro F, Massi G. Galectin-3, a marker of well-differentiated thyroid carcinoma, is expressed in thyroid nodules with cytological atypia. Histopathology. 2002;40:80ā€“7.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  14. Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov Y, Pacini F, Randolph G, Sawka A, Shepard D, Sosa J, Tuttle RM, Wartofsky L. 2015 American Thyroid Association Management Guidelines for adult patients with thyroid nodules and differentiated thyroid cancer. Available online at Thyroid 25: DOI:10.1089/thy.2015.0020; print version in Thyroid 26:1ā€“133, 2016.

    Google ScholarĀ 

  15. Cvejic D, Savin S, Paunovic I, Tatic S, Havelka M, Sinadinovic J. Immunohistochemical localization of galectin-3 in malignant and benign human thyroid tissue. Anticancer Res. 1998;18:2637ā€“41.

    CASĀ  PubMedĀ  Google ScholarĀ 

  16. Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W, Davis N, Dicks E, Ewing R, Floyd Y, Gray K, Hall S, Hawes R, Hughes J, Kosmidou V, Menzies A, Mould C, Parker A, Stevens C, Watt S, Hooper S, Wilson R, Jayatilake H, Gusterson BA, Cooper C, Shipley J, Hargrave D, Pritchard-Jones K, Maitland N, Chenevix-Trench G, Riggins GJ, Bigner DD, Palmieri G, Cossu A, Flanagan A, Nicholson A, Ho JW, Leung SY, Yuen ST, Weber BL, Seigler HF, Darrow TL, Paterson H, Marais R, Marshall CJ, Wooster R, Stratton MR, Futreal PA. Mutations of the BRAF gene in human cancer. Nature. 2002;417:949ā€“54.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  17. Elisei R, Viola D, Torregrossa L, Giannini R, Romei C, Ugolini C, Molinaro E, Agate L, Biagini A, Lupi C, Valerio L, Materazzi G, Miccoli P, Piaggi P, Pinchera A, Vitti P, Basolo F. The BRAF(V600E) mutation is an independent, poor prognostic factor for the outcome of patients with low-risk intrathyroid papillary thyroid carcinoma: single-institution results from a large cohort study. J Clin Endocrinol Metab. 2012;97:4390ā€“8.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  18. Fadda G, Rossi ED, Raffaelli M, Pontecorvi A, Sioletic S, Morassi F, Lombardi CP, Zannoni GF, Rindi G. Follicular thyroid neoplasms can be classified as low- and high-risk according to HBME-1 and Galectin-3 expression on liquid-based fine-needle cytology. Eur J Endocrinol. 2011;165:447ā€“53.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  19. Faroux MJ, Theobald S, Pluot M, Patey M, Menzies D. Evaluation of the monoclonal antibody antithyroperoxidase MoAb47 in the diagnostic decision of cold thyroid nodules by fine-needle aspiration. Pathol Res Pract. 1997;193:705ā€“12.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  20. FernĆ”ndez PL, Merino MJ, GĆ³mez M, Campo E, Medina T, Castronovo V, SanjuĆ”n X, Cardesa A, Liu FT, Sobel ME. Galectin-3 and laminin expression in neoplastic and non-neoplastic thyroid tissue. J Pathol. 1997;181:80ā€“6.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  21. Franco C, MartĆ­nez V, Allamand JP, Medina F, Glasinovic A, Osorio M, Schachter D. Molecular markers in thyroid fine-needle aspiration biopsy: a prospective study. Appl Immunohistochem Mol Morphol. 2009;17:211ā€“5.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  22. Fukahori M, Yoshida A, Hayashi H, Yoshihara M, Matsukuma S, Sakuma Y, Koizume S, Okamoto N, Kondo T, Masuda M, Miyagi Y. The associations between RAS mutations and clinical characteristics in follicular thyroid tumors: new insights from a single center and a large patient cohort. Thyroid. 2012;22:683ā€“9.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  23. Garcia-Rostan G, Zhao H, Camp RL, Pollan M, Herrero A, Pardo J, Wu R, Carcangiu ML, Costa J, Tallini G. Ras mutations are associated with aggressive tumor phenotypes and poor prognosis in thyroid cancer. J Clin Oncol. 2003;21:3226ā€“35.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  24. Guerra A, Carrano M, Angrisani E, Puzziello A, Izzo G, Di Crescenzo V, Vatrella A, Vitale M. Detection of RAS mutation by pyrosequencing in thyroid cytology samples. Int J Surg. 2014;12:S91ā€“4. pii: S1743-9191(14)00144-7.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  25. Guth S, Theune U, Aberle J, Galach A, Bamberger CM. Very high prevalence of thyroid nodules detected by high frequency (13 MHz) ultrasound examination. Eur J Clin Invest. 2009;39:699ā€“706.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  26. Herrmann ME, LiVolsi VA, Pasha TL, Roberts SA, Wojcik EM, Baloch ZW. Immunohistochemical expression of galectin-3 in benign and malignant thyroid lesions. Arch Pathol Lab Med. 2002;126:710ā€“3.

    CASĀ  PubMedĀ  Google ScholarĀ 

  27. Horn S, Figl A, Rachakonda PS, Fischer C, Sucker A, Gast A, Kadel S, Moll I, Nagore E, Hemminki K, Schadendorf D, Kumar R. TERT promoter mutations in familial and sporadic melanoma. Science. 2013;339:959ā€“61.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  28. Howlader N, Noone AM, Krapcho M, Garshell J, Miller D, Altekruse SF, et al. 2015 SEER Cancer Statistics Review, 1975-2012, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975-2012/, based on November 2014 SEER data submission, posted to the SEER web site, April 2015. Accessed on June 10, 2015.

    Google ScholarĀ 

  29. Hu S, Ewertz M, Tufano RP, Brait M, Carvalho AL, Liu D, Tufaro AP, Basaria S, Cooper DS, Sidransky D, Ladenson PW, Xing M. Detection of serum deoxyribonucleic acid methylation markers: a novel diagnostic tool for thyroid cancer. J Clin Endocrinol Metab. 2006;91:98ā€“104.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  30. Huang FW, Hodis E, Xu MJ, Kryukov GV, Chin L, Garraway LA. Highly recurrent TERT promoter mutations in human melanoma. Science. 2013;339:957ā€“9.

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  31. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69ā€“90.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  32. Joo JY, Park JY, Yoon YH, Choi B, Kim JM, Jo YS, Shong M, Koo BS. Prediction of occult central lymph node metastasis in papillary thyroid carcinoma by preoperative BRAF analysis using fine-needle aspiration biopsy: a prospective study. J Clin Endocrinol Metab. 2012;97:3996ā€“4003.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  33. Keutgen XM, Filicori F, Crowley MJ, Wang Y, Scognamiglio T, Hoda R, Buitrago D, Cooper D, Zeiger MA, Zarnegar R, Elemento O, Fahey 3rd TJ. A panel of four miRNAs accurately differentiates malignant from benign indeterminate thyroid lesions on fine needle aspiration. Clin Cancer Res. 2012;18:2032ā€“8.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  34. Keutgen XM, Filicori F, Fahey 3rd TJ. Molecular diagnosis for indeterminate thyroid nodules on fine needle aspiration: advances and limitations. Expert Rev Mol Diagn. 2013;13:613ā€“23.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  35. Kim KH, Kang DW, Kim SH, Seong IO, Kang DY. Mutations of the BRAF gene in papillary thyroid carcinoma in a Korean population. Yonsei Med J. 2004;45:818ā€“21.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  36. Kim TH, Park YJ, Lim JA, Ahn HY, Lee EK, Lee YJ, Kim KW, Hahn SK, Youn YK, Kim KH, Cho BY, do Park J. The association of the BRAF(V600E) mutation with prognostic factors and poor clinical outcome in papillary thyroid cancer: a meta-analysis. Cancer. 2012;118:1764ā€“73.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  37. Li H, Robinson KA, Anton B, Saldanha IJ, Ladenson PW. Cost-effectiveness of a novel molecular test for cytologically indeterminate thyroid nodules. J Clin Endocrinol Metab. 2011;96:E1719ā€“26.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  38. Lin KL, Wang OC, Zhang XH, Dai XX, Hu XQ, Qu JM. The BRAF mutation is predictive of aggressive clinicopathological characteristics in papillary thyroid microcarcinoma. Ann Surg Oncol. 2010;17:3294ā€“300.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  39. Liu D, Yang C, Bojdani E, Murugan AK, Xing M. Identification of RASAL1 as a major tumor suppressor gene in thyroid cancer. J Natl Cancer Inst. 2013;105:1617ā€“27.

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  40. Liu T, Wang N, Cao J, Sofiadis A, Dinets A, Zedenius J, Larsson C, Xu D. The age- and shorter telomere-dependent TERT promoter mutation in follicular thyroid cell-derived carcinomas. Oncogene. 2013. doi:10.1038/onc.2013.446 [Epub ahead of print].

    Google ScholarĀ 

  41. Liu X, Bishop J, Shan Y, Pai S, Liu D, Murugan AK, Sun H, El-Naggar AK, Xing M. Highly prevalent TERT promoter mutations in aggressive thyroid cancers. Endocr Relat Cancer. 2013;20:603ā€“10.

    ArticleĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  42. Liu X, Qu S, Liu R, Sheng C, Shi X, Zhu G, Murugan AK, Guan H, Yu H, Wang Y, Sun H, Shan Z, Teng W, Xing M. TERT promoter mutations and their association with BRAF V600E mutation and aggressive clinicopathological characteristics of thyroid cancer. J Clin Endocrinol Metab. 2014;99:E1130ā€“6.

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  43. Marotta V, Guerra A, Sapio MR, Vitale M. RET/PTC rearrangement in benign and malignant thyroid diseases: a clinical standpoint. Eur J Endocrinol. 2011;165:499ā€“507.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  44. Milas M, Shin J, Gupta M, Novosel T, Nasr C, Brainard J, Mitchell J, Berber E, Siperstein A. Circulating thyrotropin receptor mRNA as a novel marker of thyroid cancer: clinical applications learned from 1758 samples. Ann Surg. 2010;252:643ā€“51.

    PubMedĀ  Google ScholarĀ 

  45. Martins L, Matsuo SE, Ebina KN, Kulcsar MA, Friguglietti CU, Kimura ET. Galectin-3 messenger ribonucleic acid and protein are expressed in benign thyroid tumors. J Clin Endocrinol Metab. 2002;87:4806ā€“10.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  46. Mazzaferri EL. Management of a solitary thyroid nodule. N Engl J Med. 1993;328:553ā€“9.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  47. McIver B, Castro MR, Morris JC, Bernet V, Smallridge R, Henry M, Kosok L, Reddi H. An independent study of a gene expression classifier (afirmaā„¢) in the evaluation of cytologically indeterminate thyroid nodules. J Clin Endocrinol Metab. 2014;99:4069ā€“77 [Epub ahead of print].

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  48. Melo M, da Rocha AG, Vinagre J, Batista R, Peixoto J, Tavares C, Celestino R, Almeida A, Salgado C, Eloy C, Castro P, Prazeres H, Lima J, Amaro T, Lobo C, Martins MJ, Moura M, Cavaco B, Leite V, Cameselle-Teijeiro JM, Carrilho F, Carvalheiro M, MĆ”ximo V, Sobrinho-SimƵes M, Soares P. TERT promoter mutations are a major indicator of poor outcome in differentiated thyroidcarcinomas. J Clin Endocrinol Metab. 2014;99:E754ā€“65.

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  49. Milas M, Mazzaglia P, Chia SY, Skugor M, Berber E, Reddy S, Gupta M, Siperstein A. The utility of peripheral thyrotropin mRNA in the diagnosis of follicular neoplasms and surveillance of thyroid cancers. Surgery. 2007;141:137ā€“46.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  50. Mocellin S, Pooley KA, Nitti D. Telomerase and the search for the end of cancer. Trends Mol Med. 2013;19:125ā€“33.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  51. Moses W, Weng J, Sansano I, Peng M, Khanafshar E, Ljung BM, Duh QY, Clark OH, Kebebew E. Molecular testing for somatic mutations improves the accuracy of thyroid fine-needle aspiration biopsy. World J Surg. 2010;34:2589ā€“94.

    ArticleĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  52. Nikiforov YE, Steward DL, Robinson-Smith TM, Haugen BR, Klopper JP, Zhu Z, Fagin JA, Falciglia M, Weber K, Nikiforova MN. Molecular testing for mutations in improving the fine-needle aspiration diagnosis of thyroid nodules. J Clin Endocrinol Metab. 2009;94:2092ā€“8.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  53. Nikiforov YE, Ohori NP, Hodak SP, Carty SE, LeBeau SO, Ferris RL, Yip L, Seethala RR, Tublin ME, Stang MT, Coyne C, Johnson JT, Stewart AF, Nikiforova MN. 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;96:3390ā€“7.

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  54. Nucera C, Mazzon E, Caillou B, Violi MA, Moleti M, Priolo C, Sturniolo G, Puzzolo D, Cavallari V, Trimarchi F, Vermiglio F. Human galectin-3 immunoexpression in thyroid follicular adenomas with cell atypia. J Endocrinol Invest. 2005;28:106ā€“12.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  55. Rossi M, Buratto M, Bruni S, Filieri C, Tagliati F, Trasforini G, Rossi R, Beccati MD, Degli Uberti EC, Zatelli MC. Role of ultrasonographic/clinical profile, cytology, and BRAF V600E mutation evaluation in thyroid nodule screening for malignancy: a prospective study. J Clin Endocrinol Metab. 2012;97:2354ā€“61.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  56. Saggiorato E, De Pompa R, Volante M, Cappia S, Arecco F, Dei Tos AP, Orlandi F, Papotti M. Characterization of thyroid ā€˜follicular neoplasmsā€™ in fine-needle aspiration cytological specimens using a panel of immunohistochemical markers: a proposal for clinical application. Endocr Relat Cancer. 2005;12:305ā€“17.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  57. Samija I, Matea N, Lukac J, Kusic Z. Galectin-3 and CD44v6 as markers for preoperative diagnosis of thyroid cancer by RT-PCR. Diagn Mol Pathol. 2011;20:233ā€“41.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  58. Shen R, Liyanarachchi S, Li W, Wakely Jr PE, Saji M, Huang J, Nagy R, Farrell T, Ringel MD, de la Chapelle A, Kloos RT, He H. MicroRNA signature in thyroid fine needle aspiration cytology applied to ā€œatypia of undetermined significanceā€ cases. Thyroid. 2012;22:9ā€“16.

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  59. Smekalova EM, Shubernetskaya OS, Zvereva MI, Gromenko EV, Rubtsova MP, Dontsova OA. Telomerase RNA biosynthesis and processing. Biochemistry (Mosc). 2012;77:1120ā€“8.

    ArticleĀ  CASĀ  Google ScholarĀ 

  60. Song L, Tang JW, Owusu L, Sun MZ, Wu J, Zhang J. Galectin-3 in cancer. Clin Chim Acta. 2014;431:185ā€“91.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  61. Tallini G, Santoro M, Helie M, Carlomagno F, Salvatore G, Chiappetta G, Carcangiu ML, Fusco A. RET/PTC oncogene activation defines a subset of papillary thyroid carcinomas lacking evidence of progression to poorly differentiated or undifferentiated tumor phenotypes. Clin Cancer Res. 1998;4:287ā€“94.

    CASĀ  PubMedĀ  Google ScholarĀ 

  62. Tufano RP, Teixeira GV, Bishop J, Carson KA, Xing M. BRAF mutation in papillary thyroid cancer and its value in tailoring initial treatment: a systematic review and meta-analysis. Medicine (Baltimore). 2012;91:274ā€“86.

    ArticleĀ  CASĀ  Google ScholarĀ 

  63. Umbricht CB, Conrad GT, Clark DP, Westra WH, Smith DC, Zahurak M, Saji M, Smallridge RC, Goodman S, Zeiger MA. Human telomerase reverse transcriptase gene expression and the surgical management of suspicious thyroid tumors. Clin Cancer Res. 2004;10:5762ā€“8.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  64. Vinagre J, Almeida A, PĆ³pulo H, Batista R, Lyra J, Pinto V, Coelho R, Celestino R, Prazeres H, Lima L, Melo M, da Rocha AG, Preto A, Castro P, Castro L, Pardal F, Lopes JM, Santos LL, Reis RM, Cameselle-Teijeiro J, Sobrinho-SimƵes M, Lima J, MĆ”ximo V, Soares P. Frequency of TERT promoter mutations in human cancers. Nat Commun. 2013;4:2185.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  65. Volante M, Rapa I, Gandhi M, Bussolati G, Giachino D, Papotti M, Nikiforov YE. RAS mutations are the predominant molecular alteration in poorly differentiated thyroid carcinomas and bear prognostic impact. J Clin Endocrinol Metab. 2009;94:4735ā€“41.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  66. Xing M, Tufano RP, Tufaro AP, Basaria S, Ewertz M, Rosenbaum E, Byrne PJ, Wang J, Sidransky D, Ladenson PW. Detection of BRAF mutation on fine needle aspiration biopsy specimens: a new diagnostic tool for papillary thyroid cancer. J Clin Endocrinol Metab. 2004;89:2867ā€“72.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  67. Xing M, Westra WH, Tufano RP, Cohen Y, Rosenbaum E, Rhoden KJ, Carson KA, Vasko V, Larin A, Tallini G, Tolaney S, Holt EH, Hui P, Umbricht CB, Basaria S, Ewertz M, Tufaro AP, Califano JA, Ringel MD, Zeiger MA, Sidransky D, Ladenson PW. BRAF mutation predicts a poorer clinical prognosis for papillary thyroid cancer. J Clin Endocrinol Metab. 2005;90:6373ā€“9.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  68. Xing M. BRAF mutation in thyroid cancer. Endocr Relat Cancer. 2005;12:245ā€“62.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  69. Xing M. BRAF mutation in papillary thyroid cancer: pathogenic role, molecular bases, and clinical implications. Endocr Rev. 2007;28:742ā€“62.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  70. Xing M, Clark D, Guan H, Ji M, Dackiw A, Carson KA, Kim M, Tufaro A, Ladenson P, Zeiger M, Tufano R. BRAF mutation testing of thyroid fine-needle aspiration biopsy specimens for preoperative risk stratification in papillary thyroid cancer. J Clin Oncol. 2009;27:2977ā€“82.

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  71. Xing M. Genetic alterations in the phosphatidylinositol-3 kinase/Akt pathway in thyroid cancer. Thyroid. 2010;20:697ā€“706.

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  72. Xing M, Haugen BR, Schlumberger M. Progress in molecular-based management of differentiated thyroid cancer. Lancet. 2013;381:1058ā€“69.

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  73. Xing M, Alzahrani AS, Carson KA, Viola D, Elisei R, Bendlova B, Yip L, Mian C, Vianello F, Tuttle RM, Robenshtok E, Fagin JA, Puxeddu E, Fugazzola L, Czarniecka A, Jarzab B, Oā€™Neill CJ, Sywak MS, Lam AK, Riesco-Eizaguirre G, Santisteban P, Nakayama H, Tufano RP, Pai SI, Zeiger MA, Westra WH, Clark DP, Clifton-Bligh R, Sidransky D, Ladenson PW, Sykorova V. Association between BRAF V600E mutation and mortality in patients with papillary thyroid cancer. JAMA. 2013;309:1493ā€“501.

    Google ScholarĀ 

  74. Xing M. Molecular pathogenesis and mechanisms of thyroid cancer. Nat Rev Cancer. 2013;13:184ā€“99.

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  75. Xing M, Alzahrani AS, Carson KA, Shong YK, Kim TY, Viola D, Elisei R, BendlovĆ” B, Yip L, Mian C, Vianello F, Tuttle RM, Robenshtok E, Fagin JA, Puxeddu E, Fugazzola L, Czarniecka A, Jarzab B, Oā€™Neill CJ, Sywak MS, Lam AK, Riesco-Eizaguirre G, Santisteban P, Nakayama H, Clifton-Bligh R, Tallini G, Holt EH, and SĆ½korovĆ” V. Association between BRAF V600E mutation and recurrence of papillary thyroid cancer. J Clin Oncol. 2015 Jan 1;33(1):42-50

    Google ScholarĀ 

  76. Xing M, Liu R, Liu X, Murugan AK, Zhu G, Zeiger MA, Pai S, Bishop J. BRAF V600E and TERT promoter mutations cooperatively identify the most aggressive papillary thyroid cancer with highest recurrence. J Clin Oncol. 2014;32:2718ā€“26. pii: J Clin Oncol. 2014.55.5094. [Epub ahead of print].

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  77. Xu XC, el-Naggar AK, Lotan R. Differential expression of galectin-1 and galectin-3 in thyroid tumors. Potential diagnostic implications. Am J Pathol. 1995;147:815ā€“22.

    CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  78. Yip L, Farris C, Kabaker AS, Hodak SP, Nikiforova MN, McCoy KL, Stang MT, Smith KJ, Nikiforov YE, Carty SE. Cost impact of molecular testing for indeterminate thyroid nodule fine-needle aspiration biopsies. J Clin Endocrinol Metab. 2012;97:1905ā€“12.

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  79. Yip L. Molecular diagnostic testing and the indeterminate thyroid nodule. Curr Opin Oncol. 2014;26:8ā€“13.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  80. Xing M, Liu R, Bishop J. TERT promoter and BRAF mutations cooperatively promote papillary thyroid cancer-related mortality. Thyroid. 2014b; 24: Aā€“131.

    Google ScholarĀ 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine/Endocrinology and Metabolism, Johns Hopkins Hospital, 1830 East Monument Street/Suite 333, Baltimore, MD, 21287, USA

    Mingzhao Xing MD PhD

Authors
  1. Mingzhao Xing MD PhD
    View author publications

    You can also search for this author in PubMedĀ Google Scholar

Corresponding author

Correspondence to Mingzhao Xing MD PhD .

Editor information

Editors and Affiliations

  1. Department of Medicine, MedStar Washington Hospital Center Georgetown University School of Medicine, Washington, DC, USA

    Leonard Wartofsky

  2. Nuclear Medicine Research MedStar Research Institute and Washington Hospital Center, Georgetown University School of Medicine Washington Hospital Center, Washington, DC, USA

    Douglas Van Nostrand

Rights and permissions

Reprints and permissions

Copyright information

Ā© 2016 Springer Science+Business Media New York

About this chapter

Cite this chapter

Xing, M. (2016). Diagnostic and Prognostic Molecular Markers in Thyroid Cancer. In: Wartofsky, L., Van Nostrand, D. (eds) Thyroid Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-3314-3_22

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-3314-3_22

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4939-3312-9

  • Online ISBN: 978-1-4939-3314-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation