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Thyroid Cancer, Iodine, and Gene Mutation

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대한갑상선학회 (Korean Thyroid Association)|2023.05|International Journal of Thyroidology|제16권 제1호|pp. 89-95|DOI 10.11106/ijt.2023.16.1.89

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참고문헌

키워드

Thyroid carcinomaIodineBRAF mutationTERT promoter mutation
주제분류의학일반

초록

Excessive iodine intake is associated with the development of papillary thyroid carcinoma and increases the expression of BRAF mutations. In order to prevent most patients with thyroid cancer from unnecessary treatment, it is important to distinguish the patients who need aggressive treatment from those who do not. Although conventional prognostic systems alone have limitations, adding molecular tests can more accurately predict the final outcome of each patient, because molecular changes precede histological changes. Although BRAF mutation has drawn much attention on its high prevalence, it cannot predict the clinical outcome of each patient. It was no longer significant after the adjustment with other prognostic factors. The isolated BRAF mutation may be a sensitive, but not specific marker of recurrence and mortality. Recently, telomerase reverse transcriptase (TERT) promoter mutation has been identified in thyroid cancer. It increases telomerase activity, which allows cancer cells to immortalize. It was found in 10 to 20% of differentiated thyroid carcinoma and more than 40% of dedifferentiated thyroid carcinoma. It is highly prevalent in old age, large tumor, aggressive histology, advanced stages, and distant metastasis. It is strongly associated with increased recurrence and mortality, therefore, aggressive treatment is required in patients with TERT promoter mutation. Concomitant BRAF and TERT promoter mutations show the most aggressive clinical outcomes. When ultrasonography shows nonparallel orientation and microlobulated margins, especially in those older than 50 years, there is a high probability of accompanying TERT promoter mutation. Inclusion of TERT promoter mutation analysis with conventional clinicopathological evaluation can lead to better prognostication and management for individual patients.

Abstract

Excessive iodine intake is associated with the development of papillary thyroid carcinoma and increases the expression of BRAF mutations. In order to prevent most patients with thyroid cancer from unnecessary treatment, it is important to distinguish the patients who need aggressive treatment from those who do not. Although conventional prognostic systems alone have limitations, adding molecular tests can more accurately predict the final outcome of each patient, because molecular changes precede histological changes. Although BRAF mutation has drawn much attention on its high prevalence, it cannot predict the clinical outcome of each patient. It was no longer significant after the adjustment with other prognostic factors. The isolated BRAF mutation may be a sensitive, but not specific marker of recurrence and mortality. Recently, telomerase reverse transcriptase (TERT) promoter mutation has been identified in thyroid cancer. It increases telomerase activity, which allows cancer cells to immortalize. It was found in 10 to 20% of differentiated thyroid carcinoma and more than 40% of dedifferentiated thyroid carcinoma. It is highly prevalent in old age, large tumor, aggressive histology, advanced stages, and distant metastasis. It is strongly associated with increased recurrence and mortality, therefore, aggressive treatment is required in patients with TERT promoter mutation. Concomitant BRAF and TERT promoter mutations show the most aggressive clinical outcomes. When ultrasonography shows nonparallel orientation and microlobulated margins, especially in those older than 50 years, there is a high probability of accompanying TERT promoter mutation. Inclusion of TERT promoter mutation analysis with conventional clinicopathological evaluation can lead to better prognostication and management for individual patients.

참고문헌 (66)

  1. Dal Maso L, "Risk factors for thyroid cancer : an epidemiological review focused on nutritional factors", Cancer Causes Control, 20(1), pp.75~86 (2009)
  2. Ishigaki K, "Urinary iodine levels and thyroid diseases in children; comparison between Nagasaki and Chernobyl", Endocr J, 48(5), pp.591~595 (2001)
  3. Fuse Y, "Smaller thyroid gland volume with high urinary iodine excretion in Japanese schoolchildren : normative reference values in an iodinesufficient area and comparison with the WHO", ICCIDD reference, 2007, pp.17(2), 145~155
  4. Orito Y, "Thyroid function in early pregnancy in Japanese healthy women : relation to urinary iodine excretion, emesis, and fetal and child development", J Clin Endocrinol Metab, 94(5), pp.1683~1688 (2009)
  5. Kim JY, "Dietary iodine intake and urinary iodine excretion in normal Korean adults", Yonsei Med J, 39(4), pp.355~362 (1998)
  6. Kim HI, "Urinary iodine concentration and thyroid hormones : Korea National Health and Nutrition Examination Survey 2013-2015", Eur J Nutr, 58(1), pp.233~240 (2019)
  7. Burgess JR, "The changing incidence and spectrum of thyroid carcinoma in Tasmania(1978-1998)during a transition from iodine sufficiency to iodine deficiency", J Clin Endocrinol Metab, 85(4), pp.1513~1517 (2000)
  8. Feldt-Rasmussen U, "Iodine and cancer", Thyroid, 11(5), pp.483~486 (2001)
  9. Vuong HG, "Genetic alterations of differentiated thyroid carcinoma in iodine-rich and iodine-deficient countries", Cancer Med, 5(8), pp.1883~1889 (2016)
  10. Park SH, "Pathologic study on thyroid diseases among Koreans", Inje Med J, 4(4), pp.349~355 (1983)
  11. Hong EK, "A national study on biopsy-confirmed thyroid diseases among Koreans : an analysis of 7758 cases", J Korean Med Sci, 5(1), pp.1~12 (1990)
  12. Oh CM, "Decreasing trends in thyroid cancer incidence in South Korea : what happened in South Korea?", Cancer Med, 10(12), pp.4087~4096 (2021)
  13. Kim SW, "BRAFV600E mutation analysis in fine-needle aspiration cytology specimens for evaluation of thyroid nodule : a large series in a BRAFV600E-prevalent population", J Clin Endocrinol Metab, 95(8), pp.3693~3700 (2010)
  14. Kim HJ, "Strong association of relatively low and extremely excessive iodine intakes with thyroid cancer in an iodine-replete area", Eur J Nutr, 56(3), pp.965~971 (2017)
  15. Kim HJ, "Iodine intake as a risk factor for BRAF mutations in papillary thyroid cancer patients from an iodine-replete area", Eur J Nutr, 57(2), pp.809~815 (2018)
  16. Zhang X, "The relationship between urinary iodine concentration and papillary thyroid cancer : a systematic review and meta-analysis", Front Endocrinol(Lausanne), 13, pp.1049423~ (2022)
  17. Kanno J, "Tumor-promoting effects of both iodine deficiency and iodine excess in the rat thyroid", Toxicol Pathol, 20(2), pp.226~235 (1992)
  18. Vitale M, "Iodide excess induces apoptosis in thyroid cells through a p53-independent mechanism involving oxidative stress", Endocrinology, 141(2), pp.598~605 (2000)
  19. Boltze C, "Radiation-induced thyroid carcinogenesis as a function of time and dietary iodine supply : an in vivo model of tumorigenesis in the rat", Endocrinology, 143(7), pp.2584~2592 (2002)
  20. Guan H, "Association of high iodine intake with the T1799A BRAF mutation in papillary thyroid cancer", J Clin Endocrinol Metab, 94(5), pp.1612~1617 (2009)
  21. Kowalska A, "Increase in papillary thyroid cancer incidence is accompanied by changes in the frequency of the BRAF V600E mutation : a single-institution study", Thyroid, 26(4), pp.543~551 (2016)
  22. Liu XH, "Iodine mediated mechanisms and thyroid carcinoma", Crit Rev Clin Lab Sci, 46(5-6), pp.302~318 (2009)
  23. Wang F, "Strong association of high urinary iodine with thyroid nodule and papillary thyroid cancer", Tumour Biol, 35(11), pp.11375~11379 (2014)
  24. Hay ID, "Predicting outcome in papillary thyroid carcinoma : development of a reliable prognostic scoring system in a cohort of 1779patients surgically treated at one institution during 1940 through 1989", Surgery, 114(6), pp.1050~1057 (1993)
  25. Gupta N, "RAS mutations in thyroid FNA specimens are highly predictive of predominantly low-risk follicular-pattern cancers", J Clin Endocrinol Metab, 98(5), pp.E914~E922 (2013)
  26. Cancer Genome Atlas Research Network, "Integrated genomic characterization of papillary thyroid carcinoma", Cell, 159(3), pp.676~690 (2014)
  27. Chung JH, "BRAF and TERT promoter mutations : clinical application in thyroid cancer", Endocr J, 67(6), pp.577~584 (2020)
  28. Davies H, "Mutations of the BRAF gene in human cancer", Nature, 417(6892), pp.949~954 (2002)
  29. Soares P, "BRAF mutations and RET", PTC rearrangements are alternative events in the etiopathogenesis of PTC, 2003, pp.22(29), 4578~4580
  30. Kimura ET, "High prevalence of BRAF mutations in thyroid cancer : genetic evidence for constitutive activation of the RET", PTC-RAS-BRAF signaling pathway in papillary thyroid carcinoma, 2003, pp.63(7), 1454~1457
  31. Fukushima T, "BRAF mutations in papillary carcinomas of the thyroid", Oncogene, 22(41), pp.6455~6457 (2003)
  32. Namba H, "Clinical implication of hot spot BRAF mutation, V599E, in papillary thyroid cancers", J Clin Endocrinol Metab, 88(9), pp.4393~4397 (2003)
  33. Nikiforova MN, "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(11), pp.5399~5404 (2003)
  34. Jung CK, "Mutational patterns and novel mutations of the BRAF gene in a large cohort of Korean patients with papillary thyroid carcinoma", Thyroid, 22(8), pp.791~797 (2012)
  35. Nikiforov YE, "Molecular testing for mutations in improving the fine-needle aspiration diagnosis of thyroid nodules", J Clin Endocrinol Metab, 94(6), pp.2092~2098 (2009)
  36. Kim TH, "The association of the BRAF(V600E)mutation with prognostic factors and poor clinical outcome in papillary thyroid cancer : a meta-analysis", Cancer, 118(7), pp.1764~1773 (2012)
  37. Tufano RP, "BRAF mutation in papillary thyroid cancer and its value in tailoring initial treatment : a systematic review and meta-analysis", Medicine(Baltimore), 91(5), pp.274~286 (2012)
  38. Xing M, "Association between BRAF V600E mutation and mortality in patients with papillary thyroid cancer", JAMA, 309(14), pp.1493~1501 (2013)
  39. Xing M, "Association between BRAF V600E mutation and recurrence of papillary thyroid cancer", J Clin Oncol, 33(1), pp.42~50 (2015)
  40. Liu RT, "No correlation between BRAFV600E mutation and clinicopathological features of papillary thyroid carcinomas in Taiwan", Clin Endocrinol(Oxf), 63(4), pp.461~466 (2005)
  41. Kim TY, "The BRAF mutation is not associated with poor prognostic factors in Korean patients with conventional papillary thyroid microcarcinoma", Clin Endocrinol(Oxf), 63(5), pp.588~593 (2005)
  42. Ito Y, "BRAF mutation in papillary thyroid carcinoma in a Japanese population : its lack of correlation with high-risk clinicopathological features and disease-free survival of patients", Endocr J, 56(1), pp.89~97 (2009)
  43. Calado RT, "Telomere diseases", N Engl J Med, 361(24), pp.2353~2365 (2009)
  44. Shay JW, "A survey of telomerase activity in human cancer", Eur J Cancer, 33(5), pp.787~791 (1997)
  45. Huang FW, "Highly recurrent TERT promoter mutations in human melanoma", Science, 339(6122), pp.957~959 (2013)
  46. Horn S, "TERT promoter mutations in familial and sporadic melanoma", Science, 339(6122), pp.959~961 (2013)
  47. Vinagre J, "Frequency of TERT promoter mutations in human cancers", Nat Commun, 4, pp.2185~ (2013)
  48. Landa I, "Frequent somatic TERT promoter mutations in thyroid cancer : higher prevalence in advanced forms of the disease", J Clin Endocrinol Metab, 98(9), pp.E1562~E1566 (2013)
  49. Liu X, "Highly prevalent TERT promoter mutations in aggressive thyroid cancers", Endocr Relat Cancer, 20(4), pp.603~610 (2013)
  50. Liu T, "The age-and shorter telomere-dependent TERT promoter mutation in follicular thyroid cell-derived carcinomas", Oncogene, 33(42), pp.4978~4984 (2014)
  51. Liu R, "TERT promoter mutations in thyroid cancer", Endocr Relat Cancer, 23(3), pp.R143~R155 (2016)
  52. Kim TH, "TERT promoter mutations and long-term survival in patients with thyroid cancer", Endocr Relat Cancer, 23(10), pp.813~823 (2016)
  53. 양희라, "Frequency of TERT Promoter Mutations in Real-World Analysis of 2,092 Thyroid Carcinoma Patients", Endocrinology and Metabolism, 37(4), pp.652~663 (2022), 대한내분비학회[DOI]
  54. Yang X, "TERT promoter mutation predicts radioiodine-refractory character in distant metastatic differentiated thyroid cancer", J Nucl Med, 58(2), pp.258~265 (2017)
  55. Liu X, "TERT promoter mutations and their association with BRAF V600E mutation and aggressive clinicopathological characteristics of thyroid cancer", J Clin Endocrinol Metab, 99(6), pp.E1130~6 (2014)
  56. Oishi N, "Molecular alterations of coexisting thyroid papillary carcinoma and anaplastic carcinoma : identification of TERT mutation as an independent risk factor for transformation", Mod Pathol, 30(11), pp.1527~1537 (2017)
  57. Vuong HG, "Prognostic implication of BRAF and TERT promoter mutation combination in papillary thyroid carcinoma-a meta-analysis", Clin Endocrinol(Oxf), 87(5), pp.411~417 (2017)
  58. Song YS, "Interaction of BRAF-induced ETS factors with mutant TERT promoter in papillary thyroid cancer", Endocr Relat Cancer, 26(6), pp.629~641 (2019)
  59. Melo M, "TERT, BRAF, and NRAS in primary thyroid cancer and metastatic disease", J Clin Endocrinol Metab, 102(6), pp.1898~1907 (2017)
  60. Liu R, "Mortality risk stratification by combining BRAF V600E and TERT promoter mutations in papillary thyroid cancer : genetic duet of BRAF and TERT promoter mutations in thyroid cancer mortality", JAMA Oncol, 3(2), pp.202~208 (2017)
  61. Moon S, "Effects of coexistent BRAF(V600E)and TERT promoter mutations on poor clinical outcomes in papillary thyroid cancer : a meta-analysis", Thyroid, 27(5), pp.651~660 (2017)
  62. Hahn SY, "Ultrasound and clinicopathological features of papillary thyroid carcinomas with BRAF and TERT promoter mutations", Oncotarget, 8(65), pp.108946~108957 (2017)
  63. Kim TH, "Ultrasonographic prediction of highly aggressive telomerase reverse transcriptase(TERT)promoter-mutated papillary thyroid cancer", Endocrine, 57(2), pp.234~240 (2017)
  64. Tuttle RM, "Estimating risk of recurrence in differentiated thyroid cancer after total thyroidectomy and radioactive iodine remnant ablation : using response to therapy variables to modify the initial risk estimates predicted by the new American Thyroid Association staging system", Thyroid, 20(12), pp.1341~1349 (2010)
  65. Kim TH, "Refining dynamic risk stratification and prognostic groups for differentiated thyroid cancer with TERT promoter mutations", J Clin Endocrinol Metab, 102(5), pp.1757~1764 (2017)
  66. Park H, "Molecular classification of follicular thyroid carcinoma based on TERT promoter mutations", Mod Pathol, 35(2), pp.186~192 (2022)

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TERT Promoter Mutations and Tumor Persistence/Recurrence in Papillary Thyroid Cancer곽병국, 김민주, 명재경, 이명철, 임정아대한암학회 · Cancer Research and Treatment2016 · 제48권 제3호TERT mutations and aggressive histopathologic characteristics of radioiodine-refractory papillary thyroid cancer차윤진, 표주연, 홍순원대한병리학회 · Journal of Pathology and Translational Medicine2024 · 제58권 제6호Highly prevalent BRAF V600E and low-frequency TERT promoter mutations underlie papillary thyroid carcinoma in Koreans김광순, 김수연, 김정수, 김태은, 배자성, 정찬권대한병리학회 · Journal of Pathology and Translational Medicine2020 · 제54권 제4호The Clinical Significance of the BRAF Mutation in Patients with Papillary Thyroid Cancer김수정, 소의영, 이정훈대한내분비외과학회 · Journal of Endocrine Surgery2017 · 제17권 제4호Expression of Sodium-Iodide Symporter Depending on Mutational Status and Lymphocytic Thyroiditis in Papillary Thyroid Carcinoma박영주, 송영신대한갑상선학회 · International Journal of Thyroidology2018 · 제11권 제2호Surgical Extent of Low-to-Intermediate Thyroid Cancer: Molecular Testing and Clinical Decision-Making장재원대한갑상선학회 · International Journal of Thyroidology2025 · 제18권 제1호

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