Molecular genetic studies in the diagnosis of differentiated thyroid cancer: literature review
Main Article Content
The preoperative diagnosis of differentiated thyroid cancer (DTC) remains an urgent problem. During cytological evaluation of thyroid nodes, it is impossible to distinguish clearly benign and malignant pathology in 5–20 % of cases, which is especially relevant for Bethesda III and IV. Due to fear of missing the cancer, diagnostic hemi-/thyroidectomy with lymph node dissection are still being carried out in 50–70 % of cases. The operation carries certain financial costs and a potential risk to the patient. In order to optimize the diagnosis of DTC, methods of molecular genetic analysis have been used in clinical practice during recent years. This method allows identifying patients at increased risk of cancer formation and predicting the nature and activity of the process. If necessary, it determines the volume of surgical intervention — from hemithyroidectomy in case of microcarcinoma with a favorable prognosis to, otherwise, thyroidectomy with lymphadenectomy. Understanding the processes of oncogenesis of thyroid tumors using molecular genetic testing allows the doctor to reasonably provide information to the patient about the possible DTC, its form, aggressiveness, possible hereditary nature, and reduce the number (up to 69 %) of diagnostic surgical interventions with a dubious result of cytology. Given the large amount of accumulated information regarding the types of mutations of thyroid nodules and its continued rapid growth, in the near future we should expect mathematical computer modeling of the stratification of the risk of revealing DTC, its aggressiveness and further personalized therapy of the patient.
This work is licensed under a Creative Commons Attribution 4.0 International License.
Our edition uses the copyright terms of Creative Commons for open access journals.
Authors, who are published in this journal, agree with the following terms:
- The authors retain rights for authorship of their article and grant to the edition the right of first publication of the article on a Creative Commons Attribution 4.0 International License, which allows others to freely distribute the published article, with the obligatory reference to the authors of original works and original publication in this journal.
- Directing the article for the publication to the editorial board (publisher), the author agrees with transmitting of rights for the protection and using the article, including parts of the article, which are protected by the copyrights, such as the author’s photo, pictures, charts, tables, etc., including the reproduction in the media and the Internet; for distributing; for the translation of the manuscript in all languages; for export and import of the publications copies of the writers’ article to spread, bringing to the general information.
- The rights mentioned above authors transfer to the edition (publisher) for the unlimited period of validity and on the territory of all countries of the world.
- The authors guarantee that they have exclusive rights for using of the article, which they have sent to the edition (publisher). The edition (the publisher) is not responsible for the violation of given guarantees by the authors to the third parties.
- The authors have the right to conclude separate supplement agreements that relate to non-exclusive distribution of their article in the form in which it had been published in the journal (for example, to upload the work to the online storage of the journal or publish it as part of a monograph), provided that the reference to the first publication of the work in this journal is included.
- The policy of the journal permits and encourages the publication of the article in the Internet (in institutional repository or on a personal website) by the authors, because it contributes to productive scientific discussion and a positive effect on efficiency and dynamics of the citation of the article.
Baloch ZW, Fleisher S, LiVolsi VA, Gupta PK. Diagnosis of "follicular neoplasm": a gray zone in thyroid fine-needle aspiration cytology. Diagn Cytopathol. 2002;26(1):41-44. doi:10.1002/dc.10043.
Cibas ES, Ali SZ. The 2017 Bethesda System for Reporting Thyroid Cytopathology. Thyroid. 2017;27(11):1341-1346. doi:10.1089/thy.2017.0500.
Bongiovanni M, Spitale A, Faquin WC, Mazzucchelli L, Baloch ZW. The Bethesda System for Reporting Thyroid Cytopathology: a meta-analysis. Acta Cytol. 2012;56(4):333-339. doi:10.1159/000339959.
Vriens D, Adang EM, Netea-Maier RT, et al. Cost-effectiveness of FDG-PET/CT for cytologically indeterminate thyroid nodules: a decision analytic approach. J Clin Endocrinol Metab. 2014;99(9):3263-3274. doi:10.1210/jc.2013-3483.
McHenry CR, Slusarczyk SJ. Hypothyroidisim following hemithyroidectomy: incidence, risk factors, and management. Surgery. 2000;128(6):994-998. doi:10.1067/msy.2000.110242.
Jeannon JP, Orabi AA, Bruch GA, Abdalsalam HA, Simo R. Diagnosis of recurrent laryngeal nerve palsy after thyroidectomy: a systematic review. Int J Clin Pract. 2009;63(4):624-629. doi:10.1111/j.1742-1241.2008.01875.x.
Mazzaferri EL, Young RL. Papillary thyroid carcinoma: a 10 year follow-up report of the impact of therapy in 576 patients. Am J Med. 1981;70(3):511-518. doi:10.1016/0002-9343(81)90573-8.
Haugen BR, Alexander EK, Bible KC, et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016;26(1):1-133. doi:10.1089/thy.2015.0020.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69-90. doi:10.3322/caac.20107.
Choi YM, Kim WG, Kwon H, et al. Changes in standardized mortality rates from thyroid cancer in Korea between 1985 and 2015: Analysis of Korean national data. Cancer. 2017;123(24):4808-4814. doi:10.1002/cncr.30943.
Miyauchi A, Ito Y, Oda H. Insights into the Management of Papillary Microcarcinoma of the Thyroid. Thyroid. 2018;28(1):23-31. doi:10.1089/thy.2017.0227.
Lee CR, Lee S, Son H, et al. Medullary thyroid carcinoma: a 30-year experience at one institution in Korea. Ann Surg Treat Res. 2016;91(6):278-287. doi:10.4174/astr.2016.91.6.278.
Riesco-Eizaguirre G, Santisteban P. New insights in thyroid follicular cell biology and its impact in thyroid cancer therapy. Endocr Relat Cancer. 2007;14(4):957-977. doi:10.1677/ERC-07-0085.
Haugen BR, Sherman SI. Evolving approaches to patients with advanced differentiated thyroid cancer. Endocr Rev. 2013;34(3):439-455. doi:10.1210/er.2012-1038.
He L, Hannon GJ. MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet. 2004;5(7):522-531. doi:10.1038/nrg1379.
Zhang KL, Zhou X, Han L, et al. MicroRNA-566 activates EGFR signaling and its inhibition sensitizes glioblastoma cells to nimotuzumab. Mol Cancer. 2014;13:63. doi:10.1186/1476-4598-13-63.
Wang Y, Wang B, Zhou H, Zhang X, Qian X, Cui J. MicroRNA-384 Inhibits the Progression of Papillary Thyroid Cancer by Targeting PRKACB. Biomed Res Int. 2020;2020:4983420. doi:10.1155/2020/4983420.
Wang Z, He L, Sun W, et al. miRNA-299-5p regulates estrogen receptor alpha and inhibits migration and invasion of papillary thyroid cancer cell. Cancer Manag Res. 2018;10:6181-6193. doi:10.2147/CMAR.S182625.
Sui GQ, Fei D, Guo F, et al. MicroRNA-338-3p inhibits thyroid cancer progression through targeting AKT3. Am J Cancer Res. 2017;7(5):1177-1187.
Labourier E, Shifrin A, Busseniers AE, et al. Molecular Testing for miRNA, mRNA, and DNA on Fine-Needle Aspiration Improves the Preoperative Diagnosis of Thyroid Nodules With Indeterminate Cytology. J Clin Endocrinol Metab. 2015;100(7):2743-2750. doi:10.1210/jc.2015-1158.
Hu Y, Wang H, Chen E, Xu Z, Chen B, Lu G. Candidate microRNAs as biomarkers of thyroid carcinoma: a systematic review, meta-analysis, and experimental validation. Cancer Med. 2016;5(9):2602-2614. doi:10.1002/cam4.811.
Riesco-Eizaguirre G, Santisteban P. ENDOCRINE TUMOURS: Advances in the molecular pathogenesis of thyroid cancer: lessons from the cancer genome. Eur J Endocrinol. 2016;175(5):R203-R217. doi:10.1530/EJE-16-0202.
Melillo RM, Castellone MD, Guarino V, et al. The RET/PTC-RAS-BRAF linear signaling cascade mediates the motile and mitogenic phenotype of thyroid cancer cells. J Clin Invest. 2005;115(4):1068-1081. doi:10.1172/JCI22758.
Xing M. Molecular pathogenesis and mechanisms of thyroid cancer. Nat Rev Cancer. 2013;13(3):184-199. doi:10.1038/nrc3431.
Cancer Genome Atlas Research Network. Integrated genomic characterization of papillary thyroid carcinoma. Cell. 2014;159(3):676-690. doi:10.1016/j.cell.2014.09.050.
Nikiforova MN, Kimura ET, Gandhi M, et al. BRAF mutations in thyroid tumors are restricted to papillary carcinomas and anaplastic or poorly differentiated carcinomas arising from papillary carcinomas. J Clin Endocrinol Metab. 2003;88(11):5399-5404. doi:10.1210/jc.2003-030838.
Frattini M, Ferrario C, Bressan P, et al. Alternative mutations of BRAF, RET and NTRK1 are associated with similar but distinct gene expression patterns in papillary thyroid cancer. Oncogene. 2004;23(44):7436-7440. doi:10.1038/sj.onc.1207980.
Gertz RJ, Nikiforov Y, Rehrauer W, McDaniel L, Lloyd RV. Mutation in BRAF and Other Members of the MAPK Pathway in Papillary Thyroid Carcinoma in the Pediatric Population. Arch Pathol Lab Med. 2016;140(2):134-139. doi:10.5858/arpa.2014-0612-OA.
Kim MH, Bae JS, Lim DJ, et al. Quantification of BRAF V600E alleles predicts papillary thyroid cancer progression. Endocr Relat Cancer. 2014;21(6):891-902. doi:10.1530/ERC-14-0147.
Vuong HG, Altibi AM, Abdelhamid AH, et al. The changing characteristics and molecular profiles of papillary thyroid carcinoma over time: a systematic review. Oncotarget. 2017;8(6):10637-10649. doi:10.18632/oncotarget.12885.
Paschke R, Cantara S, Crescenzi A, Jarzab B, Musholt TJ, Sobrinho Simoes M. European Thyroid Association Guidelines regarding Thyroid Nodule Molecular Fine-Needle Aspiration Cytology Diagnostics. Eur Thyroid J. 2017;6(3):115-129. doi:10.1159/000468519.
Nikiforov YE, Ohori NP, Hodak SP, et al. 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(11):3390-3397. doi:10.1210/jc.2011-1469.
Alexander EK, Kennedy GC, Baloch ZW, et al. Preoperative diagnosis of benign thyroid nodules with indeterminate cytology. N Engl J Med. 2012;367(8):705-715. doi:10.1056/NEJMoa1203208.
Nikiforov YE, Steward DL, Robinson-Smith TM, et al. Molecular testing for mutations in improving the fine-needle aspiration diagnosis of thyroid nodules. J Clin Endocrinol Metab. 2009;94(6):2092-2098. doi:10.1210/jc.2009-0247.
Nikiforova MN, Wald AI, Roy S, Durso MB, Nikiforov YE. Targeted next-generation sequencing panel (ThyroSeq) for detection of mutations in thyroid cancer. J Clin Endocrinol Metab. 2013;98(11):E1852-E1860. doi:10.1210/jc.2013-2292.
Nikiforov YE, Carty SE, Chiosea SI, 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):3627-3634. doi:10.1002/cncr.29038.
Nikiforov YE, Baloch ZW. Clinical validation of the ThyroSeq v3 genomic classifier in thyroid nodules with indeterminate FNA cytology. Cancer Cytopathol. 2019;127(4):225-230. doi:10.1002/cncy.22112.
Steward DL, Carty SE, Sippel RS, et al. Performance of a Multigene Genomic Classifier in Thyroid Nodules With Indeterminate Cytology: A Prospective Blinded Multicenter Study. JAMA Oncol. 2019;5(2):204-212. doi:10.1001/jamaoncol.2018.4616.
Vargas-Salas S, Martínez JR, Urra S, et al. Genetic testing for indeterminate thyroid cytology: review and meta-analysis. Endocr Relat Cancer. 2018;25(3):R163-R177. doi:10.1530/ERC-17-0405.
Alexander EK, Schorr M, Klopper J, et al. Multicenter clinical experience with the Afirma gene expression classifier. J Clin Endocrinol Metab. 2014;99(1):119-125. doi:10.1210/jc.2013-2482.
Patel KN, Angell TE, Babiarz J, et al. Performance of a Genomic Sequencing Classifier for the Preoperative Diagnosis of Cytologically Indeterminate Thyroid Nodules. JAMA Surg. 2018;153(9):817-824. doi:10.1001/jamasurg.2018.1153.
Harrell RM, Eyerly-Webb SA, Golding AC, Edwards CM, Bimston DN. Statistical Comparison Of Afirma Gsc And Afirma Gec Outcomes In A Community Endocrine Surgical Practice: Early Findings. Endocr Pract. 2019;25(2):161-164. doi:10.4158/EP-2018-0395.
Endo M, Nabhan F, Porter K, et al. Afirma Gene Sequencing Classifier Compared with Gene Expression Classifier in Indeterminate Thyroid Nodules. Thyroid. 2019;29(8):1115-1124. doi:10.1089/thy.2018.0733.