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Anaplastic thyroid cancer, tumorigenesis and therapy

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Irish Journal of Medical Science Aims and scope Submit manuscript

Abstract

Background

Anaplastic thyroid cancer (ATC) is a fatal endocrine malignancy. Current therapy fails to significantly improve survival. Recent insights into thyroid tumorigenesis, post-malignant dedifferentiation and mode of metastatic activity offer new therapeutic strategies.

Methods

An extensive literature search of Medline and Pubmed was conducted to include all published reports on ATC. Secondary articles were identified from key paper reference listings.

Conclusions

Significant progress, in the last 5 years, has been made outlining thyroid tumorigenesis and the progression to anaplasia. Continued identification and development of drug therapies is required to counter specific molecular targets responsible for the post-malignant dedifferentiation process and ultimately the fatal neoplastic phenotype.

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References

  1. Are C, Shaha AR (2006) Anaplastic thyroid carcinoma: biology, pathogenesis, prognostic factors, and treatment approaches. Ann Surg Oncol 13:453–464. doi:10.1245/ASO.2006.05.042

    Article  PubMed  Google Scholar 

  2. Ain KB (1998) Anaplastic thyroid carcinoma: behavior, biology, and therapeutic approaches. Thyroid 8:715–726. doi:10.1089/thy.1998.8.715

    Article  CAS  PubMed  Google Scholar 

  3. Albores-Saavedra J, Henson DE, Glazer E et al (2007) Changing patterns in the incidence and survival of thyroid cancer with follicular phenotype-papillary, follicular, and anaplastic: a morphological and epidemiological study. Endocr Pathol 18:1–7. doi:10.1007/s12022-007-0002-z

    Article  PubMed  Google Scholar 

  4. Kobayashi TK, Asakawa H, Umeshita K et al (1996) Treatment of 37 patients with anaplastic carcinoma of the thyroid. Head Neck 18:36–41. doi:10.1002/(SICI)1097-0347(199601/02)18:1<36::AID-HED5>3.0.CO;2-#

    Article  CAS  PubMed  Google Scholar 

  5. Kim TY, Kim KW, Jung TS et al (2007) Prognostic factors for Korean patients with anaplastic thyroid carcinoma. Head Neck 29:765–772. doi:10.1002/hed.20578

    Article  PubMed  Google Scholar 

  6. Sugitani I, Kasai N, Fujimoto Y et al (2001) Prognostic factors and therapeutic strategy for anaplastic carcinoma of the thyroid. World J Surg 25:617–622. doi:10.1007/s002680020166

    Article  CAS  PubMed  Google Scholar 

  7. Delellis RA (2006) Pathology and genetics of thyroid carcinoma. J Surg Oncol 94:662–669. doi:10.1002/jso.20700

    Article  CAS  PubMed  Google Scholar 

  8. Saltman B, Singh B, Hedvat CV et al (2006) Patterns of expression of cell cycle/apoptosis genes along the spectrum of thyroid carcinoma progression. Surgery 140:899–905. doi:10.1016/j.surg.2006.07.027

    Article  PubMed  Google Scholar 

  9. Wiseman SM, Loree TR, Rigual NR et al (2003) Anaplastic transformation of thyroid cancer: review of clinical, pathologic, and molecular evidence provides new insights into disease biology and future therapy. Head Neck 25:662–670. doi:10.1002/hed.10277

    Article  PubMed  Google Scholar 

  10. Wiseman SM, Masoudi H, Niblock P et al (2007) Anaplastic thyroid carcinoma: expression profile of targets for therapy offers new insights for disease treatment. Ann Surg Oncol 14:719–729. doi:10.1245/s10434-006-9178-6

    Article  PubMed  Google Scholar 

  11. Wiseman SM, Griffith OL, Deen S et al (2007) Identification of molecular markers altered during transformation of differentiated into anaplastic thyroid carcinoma. Arch Surg 142:727–729

    Google Scholar 

  12. Nikiforova MN, Kimura ET, Gandhi M et al (2003) BRAF mutations in thyroid tumors are restricted to papillary carcinomas and anaplastic or poorly differentiated carcinomas arising from papillary carcinomas. J Clin Endocrinol Metab 88:5399–5404. doi:10.1210/jc.2003-030838

    Article  CAS  PubMed  Google Scholar 

  13. Lemoine NR, Mayall ES, Wyllie FS et al (1989) High frequency of ras oncogene activation in all stages of human thyroid tumorigenesis. Oncogene 4:159–164

    CAS  PubMed  Google Scholar 

  14. Quiros RM, Ding HG, Gattuso P et al (2005) Evidence that one subset of anaplastic thyroid carcinomas are derived from papillary carcinomas due to BRAF and p53 mutations. Cancer 103:2261–2268. doi:10.1002/cncr.21073

    Article  CAS  PubMed  Google Scholar 

  15. Segev DL, Umbricht C, Zeiger MA (2003) Molecular pathogenesis of thyroid cancer. Surg Oncol 12:69–90. doi:10.1016/S0960-7404(03)00037-9

    Article  PubMed  Google Scholar 

  16. Lam KY, Lo CY, Chan KW et al (2000) Insular and anaplastic carcinoma of the thyroid. A 45 year comparative study at a single institution and review of the significance of p53 and p21. Ann Surg 231:329–338. doi:10.1097/00000658-200003000-00005

    Article  CAS  PubMed  Google Scholar 

  17. Moretti F, Nanni S, Farsetti A et al (2000) Effects of exogenous p53 transduction in thyroid tumor cells with different p53 status. J Clin Endocrinol Metab 85:302–308. doi:10.1210/jc.85.1.302

    Article  CAS  PubMed  Google Scholar 

  18. LaPerle KM, Jhiang SM, Capen CC (2000) Loss of p53 promotes anaplasia and local invasion in ret/PTC1-induced thyroid carcinomas. Am J Pathol 157:671–677

    CAS  Google Scholar 

  19. Nakashima M, Takamura N, Namba H et al (2007) RET oncogene amplification in thyroid cancer: correlations with radiation-associated and high grade malignancy. Hum Pathol 38:621–628. doi:10.1016/j.humpath.2006.10.013

    Article  CAS  PubMed  Google Scholar 

  20. Santoro M, Papotti M, Chiappetta G et al (2002) RET activation and clinicopathologic features in poorly differentiated thyroid tumors. J Clin Endocrinol Metab 87:370–379. doi:10.1210/jc.87.1.370

    Article  CAS  PubMed  Google Scholar 

  21. Shannon KB, Salmon ED (2002) Chromosome dynamics: new light on Aurora B kinase function. Curr Biol 12:458–460. doi:10.1016/S0960-9822(02)00945-4

    Article  Google Scholar 

  22. Ulisse S, Delcros JG, Baldini E et al (2006) Expression of Aurora kinases in human thyroid carcinoma cell lines and tissues. Int J Cancer 119:275–282. doi:10.1002/ijc.21842

    Article  CAS  PubMed  Google Scholar 

  23. Sorrentino R, Libertini S, Pallante PL et al (2005) Aurora B overexpression associates with the thyroid carcinoma undifferentiated phenotype and is required for thyroid carcinoma cell proliferation. J Clin Endocrinol Metab 90:928–935. doi:10.1210/jc.2004-1518

    Article  CAS  PubMed  Google Scholar 

  24. Lim SC, Lee MS (2002) Significance of E-cadherin/beta-catenin complex and cyclin D1 in breast cancer. Oncol Rep 9:915–928

    CAS  PubMed  Google Scholar 

  25. Barton MC, Akli S, Keyomarsi K (2006) Deregulation of cyclin E meets dysfunction in p53: closing the escape hatch on breast cancer. J Cell Physiol 209:686–694. doi:10.1002/jcp.20818

    Article  CAS  PubMed  Google Scholar 

  26. Musgrove EA (2006) Cyclins: roles in mitogenic signaling and oncogenic transformation. Growth Factors 24:13–19. doi:10.1080/08977190500361812

    Article  CAS  PubMed  Google Scholar 

  27. Fagin JA, Matsuo K, Karmakar A et al (1993) High prevalence of mutations of the p53 gene in poorly differentiated human thyroid carcinomas. J Clin Invest 91:179–184. doi:10.1172/JCI116168

    Article  CAS  PubMed  Google Scholar 

  28. Garcia-Rostan G, Tallini G, Herrero A et al (1999) Frequent mutation and nuclear localization of beta-catenin in anaplastic thyroid carcinoma. Cancer Res 59:1811–1815

    CAS  PubMed  Google Scholar 

  29. Wiseman SM, Masoudi H, Niblock P et al (2006) Derangement of the E-cadherin/catenin complex is involved in transformation of differentiated to anaplastic thyroid carcinoma. Am J Surg 191:581–587. doi:10.1016/j.amjsurg.2006.02.005

    Article  CAS  PubMed  Google Scholar 

  30. Rocha AS, Soares P, Fonseca E, Cameselle-Teijeiro J et al (2003) E-cadherin loss rather than beta-catenin alterations is a common feature of poorly differentiated thyroid carcinomas. Histopathology 42:580–587. doi:10.1046/j.1365-2559.2003.01642.x

    Article  CAS  PubMed  Google Scholar 

  31. Garcia-Rostan G, Camp RL, Herrero A et al (2001) Beta-catenin dysregulation in thyroid neoplasms: down-regulation, aberrant nuclear expression, and CTNNB1 exon 3 mutations are markers for aggressive tumor phenotypes and poor prognosis. Am J Pathol 158:987–996

    CAS  PubMed  Google Scholar 

  32. Hou P, Liu D, Shan Y et al (2007) Genetic alterations and their relationship in the phosphatidylinositol 3-kinase/Akt pathway in thyroid cancer. Clin Cancer Res 13:1161–1170. doi:10.1158/1078-0432.CCR-06-1125

    Article  CAS  PubMed  Google Scholar 

  33. Garcia-Rostan G, Costa AM, Pereira-Castro I et al (2005) Mutation of the PIK3CA gene in anaplastic thyroid cancer. Cancer Res 65:10199–10207. doi:10.1158/0008-5472.CAN-04-4259

    Article  CAS  PubMed  Google Scholar 

  34. Ensinger C, Spizzo G, Moser P et al (2004) Epidermal growth factor receptor as a novel therapeutic target in anaplastic thyroid carcinomas. Ann NY Acad Sci 1030:69–77. doi:10.1196/annals.1329.009

    Article  CAS  PubMed  Google Scholar 

  35. Viglietto G, Maglione D, Rambaldi M et al (1995) Upregulation of vascular endothelial growth factor (VEGF) and downregulation of placenta growth factor (PIGF) associated with malignancy in human thyroid tumors and cell lines. Oncogene 11:1569–1579

    CAS  PubMed  Google Scholar 

  36. Prichard CN, Kim S, Yazici YD et al (2007) Concurrent cetuximab and bevacizumab therapy in a murine orthotopic model of anaplastic thyroid carcinoma. Laryngoscope 117:674–679. doi:10.1097/MLG.0b013e318031055e

    Article  CAS  PubMed  Google Scholar 

  37. Kim S, Prichard CN, Younes MN et al (2006) Cetuximab and irinotecan interact synergistically to inhibit the growth of orthotopic anaplastic thyroid carcinoma xenografts in nude mice. Clin Cancer Res 12:600–607. doi:10.1158/1078-0432.CCR-05-1325

    Article  CAS  PubMed  Google Scholar 

  38. Kim S, Schiff BA, Yigitbasi OG et al (2005) Targeted molecular therapy of anaplastic thyroid carcinoma with AEE788. Mol Cancer Ther 4:632–640. doi:10.1158/1535-7163.MCT-04-0293

    Article  CAS  PubMed  Google Scholar 

  39. Hoffman S, Burchert A, Wunderlich A et al (2007) Differential effects of cetuximab and AEE 788 on epidermal growth factor receptor (EGF-R) and vascular endothelial growth factor receptor (VEGF-R) in thyroid cancer cell lines. Endocrine 31:105–113. doi:10.1007/s12020-007-0008-9

    Article  Google Scholar 

  40. Yohoi K, Thaker PH, Yazici S et al (2005) Dual inhibition of epidermal growth factor receptor and vascular endothelial growth factor receptor phosphorylation by AEE788 reduces growth and metastasis of human colon carcinoma in an orthotopic nude mouse model. Cancer Res 65:3716–3725. doi:10.1158/0008-5472.CAN-04-3700

    Article  Google Scholar 

  41. Kim S, Yazici YD, Calzada G et al (2007) Sorafenib inhibits the angiogenesis and growth of orthotopic anaplastic thyroid carcinoma xenografts in nude mice. Mol Cancer Ther 6:1785–1792. doi:10.1158/1535-7163.MCT-06-0595

    Article  CAS  PubMed  Google Scholar 

  42. Smit JW, Schroder-van der Elst JP, Karperien M et al (2007) Iodide kinetics and experimental (131)I therapy in a xenotransplanted human sodium-iodide symporter-transfected human follicular thyroid carcinoma cell line. J Clin Endocrinol Metab 87:1247–1253. doi:10.1210/jc.87.3.1247

    Article  Google Scholar 

  43. Hsieh YJ, Ke CC, Liu RS et al (2007) Radioiodide imaging and treatment of ARO cancer xenograft in a mouse model after expression of human sodium iodide symporter. Anticancer Res 27:2515–2522

    CAS  PubMed  Google Scholar 

  44. Lee YJ, Chung JK, Shin JH et al (2004) In vitro and in vivo properties of a human anaplastic thyroid carcinoma cell line transfected with the sodium iodide symporter gene. Thyroid 14:889–895. doi:10.1089/thy.2004.14.889

    Article  PubMed  Google Scholar 

  45. Jeong H, Kim YR, Kim KN et al (2006) Effect of all-trans retinoic acid on sodium/iodide symporter expression, radioiodine uptake and gene expression profiles in a human anaplastic thyroid carcinoma cell line. Nucl Med Biol 33:875–882. doi:10.1016/j.nucmedbio.2006.07.004

    Article  CAS  PubMed  Google Scholar 

  46. Presta I, Arturi F, Ferretti E et al (2005) Recovery of NIS expression in thyroid cancer cells by overexpression of Pax8 gene. BMC Cancer 5:80. doi:10.1186/1471-2407-5-80

    Article  PubMed  Google Scholar 

  47. Sugawara I, Masunaga A, Itoyama S et al (1995) Expression of multidrug resistance-associated protein (MRP) in thyroid cancers. Cancer Lett 95:135–138. doi:10.1016/0304-3835(95)03878-z

    Article  CAS  PubMed  Google Scholar 

  48. Yasuhisa K, Shin-ya M, Michinori M et al (2007) Mechanism of multidrug recognition by MDR1/ABCB1. Cancer Sci 98:1303–1310. doi:10.1111/j.1349-7006.2007.00538.x

    Article  Google Scholar 

  49. Touhey S, O’Connor R, Plunkett S et al (2002) Structure-activity relationship of indomethacin analogues for MRP-1, COX-1 and COX-2 inhibition: identification of novel chemotherapeutic drug resistance modulators. Eur J Cancer 38:1661–1670. doi:10.1016/S0959-8049(02)00128-4

    Article  CAS  PubMed  Google Scholar 

  50. Brignardello E, Gallo M, Baldi I et al (2007) Anaplastic thyroid carcinoma: clinical outcome of 30 consecutive patients referred to a single institution in the past 5 years. Eur J Endocrinol 156:425–430. doi:10.1530/EJE-06-0677

    Article  CAS  PubMed  Google Scholar 

  51. Kebebew E, Greenspan FS, Clark OH et al (2005) Anaplastic thyroid carcinoma. Treatment outcome and prognostic factors. Cancer 103:1330–1335. doi:10.1002/cncr.20936

    Article  PubMed  Google Scholar 

  52. Pierie JP, Muzikansky A, Gaz RD et al (2002) The effect of surgery and radiotherapy on outcome of anaplastic thyroid carcinoma. Ann Surg Oncol 9:57–64. doi:10.1245/aso.2002.9.1.57

    Article  PubMed  Google Scholar 

  53. Lang BH, Lo CY (2007) Surgical options in undifferentiated thyroid carcinoma. World J Surg 31:969–977. doi:10.1007/s00268-007-0776-7

    Article  PubMed  Google Scholar 

  54. Voigt W, Kegel T, Weiss M et al (2005) Potential activity of paclitaxel, vinorelbine and gemcitabine in anaplastic thyroid carcinoma. J Cancer Res Clin Oncol 131:585–590. doi:10.1007/s00432-005-0673-0

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

There was no financial incentive or input into this article.

Conflict of interest statement

There are no conflicts of interest.

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Authors and Affiliations

  1. The Department of Otolaryngology, The Royal College of Surgeons in Ireland, Beaumont Hospital, The Education and Research Building, Beaumont, Dublin 9, Ireland

    J. P. O’Neill & M. Walsh

  2. Department of Oncology, Memorial Sloan Kettering Cancer Center, New York, USA

    D. Power

  3. The Department of Surgery, The Royal College of Surgeons in Ireland, Beaumont Hospital, The Education and Research Building, Beaumont, Dublin, Ireland

    C. Condron & D. Bouchier-Hayes

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  1. J. P. O’Neill
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  2. D. Power
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  3. C. Condron
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  4. D. Bouchier-Hayes
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  5. M. Walsh
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Correspondence to J. P. O’Neill.

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O’Neill, J.P., Power, D., Condron, C. et al. Anaplastic thyroid cancer, tumorigenesis and therapy. Ir J Med Sci 179, 9–15 (2010). https://doi.org/10.1007/s11845-009-0364-y

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