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Prognostic value of somatic mutation testing and different methods of treatment of low-risk differentiated thyroid cancer

Abstract

Background: Using molecular testing for prediction the course of the disease could possibly help doctors in making therapeutic decisions about the management of patients, because it remains controversial issues in low-risk differentiated thyroid cancer patients. The expert’s opinions are different on the volume of treatment of these patients: the adequacy of hemitireoidectomy, the need to remove the lymph nodes of the central zone (level VI) and the need for radioiodine therapy.


Aims: to evaluate the frequency of recurrences in different complex treatment options of low-risk differentiated thyroid cancer; to evaluate the frequency of somatic mutations in the hot spots of BRAF, KRAS, KRAS, EIF1AX and TERT genes in histological material and to evaluate their prognostic value.


Materials and methods: A prospective, observational, cohort, sample, single-center, open-label, controlled, nonrandomized clinical trial was performed, which included patients with the thyroid neoplasms, recruited in the period from 2012 to 2014. Samples of histological material were tested for the presence of somatic mutations in hot spots of the genes BRAF, KRAS, NRAS, TERT, and EIF1AX. After the treatment, the low-risk differentiated thyroid cancer patients group were observed for 43–68 months.


Results: The study included 90 patients with low-risk well differentiated thyroid cancer. Mutations in the hot spots of the BRAF gene (exon 15, codon area 600-601) were found in 53 patients, mutations in the hot spots of the NRAS gene (exon 3, codon 61) – in 3 patients; mutations in the hot spots of the KRAS, TERT and EIF1AX genes were not detected. The median follow-up in the well differentiated thyroid cancer group was 56 months. Recurrence diagnosed in 12 patients (13.3%), significant differences in the frequency of recurrence depending on the surgical treatment option was not revealed, significant differences in the frequency of recurrence between the groups BRAF+/BRAF was not revealed.


Conclusions: Low-risk well differentiated thyroid cancer patients have characterized a very favorable the course of disease and prognosis, even in the case of recurrence. In this study, complex treatment has not shown significant advantages over thyroidectomy in treating patients with thyroid microcarcinomas. Mutation testing of histological material in hot spots of genes BRAF, KRAS, NRAS, EIF1AX and TERT can’t be used as an additional marker in low-risk well differentiated thyroid cancer patients to predict the course of the disease, although the lack of detection of aggressive genes of the disease may indicate a favorable prognosis in these patients.

About the Authors

Vera A. Kachko
I.M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

postgraduate student



Vladimir E. Vanushko
Endocrinology Research Centre
Russian Federation

MD, PhD



Nadezhda M. Platonova
Endocrinology Research Centre,
Russian Federation

MD, PhD



References

1. Бельцевич Д.Г., Ванушко В.Э., Румянцев П.О. и др. Российские клинические рекомендации по диагностике и лечению высокодифференцированного рака щитовидной железы у взрослых, 2017 год. // Эндокринная хирургия. – 2017. – Т. 11. – №1. – С. 6-27. doi: https://doi.org/10.14341/serg201716-27. [Beltsevich DG, Vanushko VE, Rumyantsev PO, et al. 2017 Russian clinical practice guidelines for differentiated thyroid cancer diagnosis and treatment. Endocrine Surgery. 2017;11(1):6-27. doi: https://doi.org/10.14341/serg201716 -27. (In Russ.)]

2. Xing M. Molecular pathogenesis and mechanisms of thyroid cancer. Nat Rev Cancer. 2013;13(3):184-199. doi: https://doi.org/10.1038/nrc3431.

3. Younis E. Oncogenesis of thyroid cancer. Asian Pac J Cancer Prev. 2017;18(5):1191-1199. Published. doi: https://doi.org/10.22034/APJCP.2017.18.5.1191.

4. Tufano RP, Teixeira GV, Bishop J, et al. BRAF mutation in papillary thyroid cancer and its value in tailoring initial treatment: a systematic review and meta-analysis. Medicine (Baltimore). 2012;91:274-286.

5. Xing M, Alzahrani AS, Carson KA, et al. Association between BRAF V600E mutation and mortality in patients with papillary thyroid cancer. JAMA. 2013;309:1493-1501.

6. Howell GM, Hodak SP, Yip L. RAS mutations in thyroid cancer. Oncologist. 2013;18(8):926-932.

7. Gandolfi G., Ragazzi M., Frasoldati A., et al. TERT promoter mutations are associated with distant metastases in papillary thyroid carcinoma. Eur J Endocrinol. 2015;172:403-413. doi: https://doi.org/10.1530/EJE-14-0837.

8. Liu X., Qu S., Liu R., et al. TERT promoter mutations and their association with BRAF V600E mutation and aggressive clinicopathological characteristics of thyroid cancer. J Clin Endocrinol Metab. 2014;99:E1130-E1136. doi: https://doi.org/10.1210/jc.2013-4048.

9. Liu T., Yuan X., Xu D. Cancer-Specific Telomerase Reverse Transcriptase (TERT) promoter mutations: biological and clinical implications. Genes. 2016;7(7):38. doi: https://doi.org/10.3390/genes7070038.

10. Liu X, Bishop J, Shan Y, et al. Highly prevalent TERT promoter mutations in aggressive thyroid cancers. Endocr Relat Cancer. 2013;20:603-610.

11. Liu R., Xing M. TERT promoter mutations in thyroid cancer. Endocr Relat Cancer. 2016;23(3):R143-R155. doi: https://doi.org/10.1530/ERC-15-0533.

12. Jin A., Xu J., Wang Y. The role of TERT promoter mutations in postoperative and preoperative diagnosis and prognosis in thyroid cancer. Medicine (Baltimore). 2018;97(29):e11548. doi: https://doi.org/10.1097/MD.0000000000011548.

13. Karunamurthy A, Panebianco F, J Hsiao S, et al. Prevalence and phenotypic correlations of EIF1AX mutations in thyroid nodules. Endocr Relat Cancer. 2016;23(4):295-301. doi: https://doi.org/10.1530/ERC-16-0043.

14. Abdullah MI, Junit SM, Ng KL, et al. Papillary thyroid cancer: genetic alterations and molecular biomarker investigations. Int J Med Sci. 2019;16(3):450-460. Published 2019 Feb 28. doi: https://doi.org/10.7150/ijms.29935

15. COSMIC [Internet]. Catalogue of somatic mutations in cancer [cited 2018 Dec 12]. Available from: https://cancer.sanger.ac.uk/cosmic.

16. EnsEMBL [Internet]. Genome browser [cited 2018 Dec 12]. Available from: http://www.ensembl.org.


Supplementary files

1. research scheme
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2. Table 1. Characteristics of patients included in the study.
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3. Table 2. Characteristics of patients in the group of vdtc, divided into groups depending on the treatment.
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4. Table 3. The frequency of mutations in the "hot spots" of the BRAF gene (exon 15, codon area 600-601) in the histological material.
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5. Table 4. The frequency of mutations in the "hot spots" of the KRAS gene (exon 3, codon area 61) in the histological material.
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6. Table 5. Frequency and duration of dynamic follow-up of patients in the vdtc GROUP.
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7. Table 6. Characteristics of patients with VDTC (n=90) depending on the presence of BRAF mutation.
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8. Table 7. The frequency of BRAF mutation and recurrence rate depending on different surgical treatment options (n, %).
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9. Рис. 2
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10. Table 3. Characteristics of patients with VDRT (n=90) depending on the development of relapse.
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11. Table 4. Duration of dynamic follow-up, recurrence rate and frequency of BRAF mutation in different treatment options
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12. Table 5. The frequency of mutations in the "hot spots" of the BRAF gene (exon 15, codon area 600-601) in the histological material
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13. Table 6. The frequency of mutations in the "hot spots" of the KRAS gene (exon 3, codon area 61) in the histological material.
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14. Table 7. Characteristics of patients with VDRT (n=90) depending on the presence of BRAF mutation.
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15. Fig. 1. Study design.
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16. Fig. 2. Time to relapse and the incidence of BRAF and NRAS mutations in patients with relapse.
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Review

For citations:


Kachko V.A., Vanushko V.E., Platonova N.M. Prognostic value of somatic mutation testing and different methods of treatment of low-risk differentiated thyroid cancer. Endocrine Surgery. 2019;13(2):75-88. (In Russ.)

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ISSN 2306-3513 (Print)
ISSN 2310-3965 (Online)