Assessment of BRAF-V600E, KRAS, NRAS and EGFR mutations in papillary thyroid carcinoma and Hashimoto’s thyroiditis

Year 2020, , 300 - 305, 25.08.2020

Osman İlkay Özdamar , Gül Özbilen Acar Filiz Özen , Tülay Zenginkinet

https://doi.org/10.32448/entupdates.711666

Abstract

Objective: The present study compared three study groups composed of patients with only papillary thyroid carcinoma (PTC), patients with only Hashimoto’s thyroiditis (HT) and patients with PTC+HT in terms of BRAF-V600E, KRAS, NRAS and epidermal growth factor receptor (EGFR) mutations. Also, the association between clinicopathological prognostic indicators including tumor multifocality, extrathyroidal extension (ETE), lymph node (LN) metastasis and recurrence and BRAF-V600E mutations were investigated in the PTC and PTC+HT groups.

Methods: A total of 53 patients (two males and 51 females) who underwent a hemi/total thyroidectomy due to suspicion of malignancy or malignant lesion according to the thyroid cytopathology participated in the study. The study groups were composed of 19 patients with PTC, 18 with PTC+HT and 16 with HT according to the histopathological examination records. Histopathological sections from the paraffin blocks of the patients were investigated for BRAF-V600E, KRAS, NRAS and EGFR gene mutations using real-time polymerase chain reaction (PCR) assay.

Results: There was no significant difference between the groups in terms of BRAF-V600E KRAS, NRAS and EGFR mutation rates. Also, presence of the BRAF-V600E mutation was not correlated with the prognostic indicators for the patients with PTC and PTC+HT.

Conclusion: In the present study, no significant association was found between PTC and HT, and the BRAF-V600E, KRAS, NRAS and EGFR mutations. Further studies with a larger number of patients may help to clarify the clinicopathological and diagnostic importance of the BRAF-V600E, KRAS, NRAS and EGFR mutations in thyroid diseases.

Keywords

Papillary Thyroid Carcinoma, Hashimoto’s Thyroiditis, BRAF Kinases, K-ras Oncogenes, Mutation

References

• 1. Liu X, Yan K, Lin X, et al. The association between BRAF (V600E) mutation and pathological features in PTC. Eur Arch Otorhinolaryngol 2014;271:3041-52. 2. Shi CL, Sun Y, Ding C, Lv YC, Qin HD. Correlation between the BRAF V600E mutation status and the clinicopathologic features of papillary thyroid carcinoma. Genet Mol Res 2015;14:7377-85.
• 3. Kim WW, Ha TK, Bae SK. Clinical implications of the BRAF mutation in papillary thyroid carcinoma and chronic lymphocytic thyroiditis. J Otolaryngol Head Neck Surg 2018;47:4.
• 4. Jameson J, Weetman A. Disorders of the Thyroid Gland. In: Fauci A, Braunwald E, Kasper D, et al, editors. Harrison’s Principles of Internal Medicine. 17th ed. New York, NY: McGraw-Hill; 2008. p. 2224-47.
• 5. Sadow PM, Heinrich MC, Corless CL, Fletcher JA, Nosé V. Absence of BRAF, NRAS, KRAS, HRAS mutations, and RET/PTC gene rearrangements distinguishes dominant nodules in Hashimoto thyroiditis from papillary thyroid carcinomas. Endocr Pathol 2010;21:73-9.
• 6. Dailey ME, Lindsay S, Skahen R. Relation of thyroid neoplasm to Hashimoto disease of the thyroid gland. AMA Arch Surg 1955;70:291-7.
• 7. Kim KW, Park YJ, Kim EH, et al. Elevated risk of papillary thyroid cancer in Korean patients with Hashimoto's thyroiditis. Head Neck 2011;33:691-5.
• 8. Niault TS, Baccarini M. Targets of Raf in tumorigenesis. Carcinogenesis 2010;31:1165-74.
• 9. Rowe LR, Bentz BG, Bentz JS. Detection of BRAF V600E activating mutation in papillary thyroid carcinoma using PCR with allele-specific fluorescent probe melting curve analysis. J Clin Pathol 2007;60:1211-5.
• 10. Elisei R, Ugolini C, Viola D, et al. BRAF(V600E) mutation and outcome of patients with papillary thyroid carcinoma: a 15-year median follow-up study. J Clin Endocrinol Metab 2008;93:3943-9.
• 11. Crespo P, León J. Ras proteins in the control of the cell cycle and cell differentiation. Cell Mol Life Sci 2000;57:1613-36.
• 12. Prior IA, Lewis PD and Mattos C. A comprehensive survey of RAS mutations in cancer. Cancer Res 2012;72:2457-67.
• 13. Schulten HJ, Salama S, Al-Ahmadi A, et al. Comprehensive survey of HRAS, KRAS, and NRAS mutations in proliferative thyroid lesions from an ethnically diverse population. Anticancer Res 2013;33:4779-84.
• 14. Nikiforov YE, Nikiforova MN. Molecular genetics and diagnosis of thyroid cancer. Nat Rev Endocrinol 2011;7:569-80.
• 15. Fisher KE, Jani JC, Fisher SB, et al. Epidermal growth factor receptor overexpression is a marker for adverse pathologic features in papillary thyroid carcinoma. J Surg Res 2013;185:217-24.
• 16. Hoffmann S, Burchert A, Wunderlich A, et al. 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 2007;31:105-13.
• 17. Lee DH, Lee GK, Kong SY, et al. Epidermal growth factor receptor status in anaplastic thyroid carcinoma. J Clin Pathol 2007;60:881-4.
• 18. Zhu Z, Gandhi M, Nikiforova MN, Fischer AH, Nikiforov YE. Molecular profile and clinical-pathologic features of the follicular variant of papillary thyroid carcinoma. An unusually high prevalence of ras mutations. Am J Clin Pathol 2003;120:71-7.
• 19. Vasko V, Ferrand M, Di Cristofaro J, Carayon P, Henry JF, de Micco C. Specific pattern of RAS oncogene mutations in follicular thyroid tumors. J Clin Endocrinol Metab 2003;88:2745-52.
• 20. Elliott DD, Sherman SI, Busaidy NL, et al. Growth factor receptors expression in anaplastic thyroid carcinoma: potential markers for therapeutic stratification. Hum Pathol 2008;39:15-20.
• 21. Masago K, Asato R, Fujita S, et al. Epidermal growth factor receptor gene mutations in papillary thyroid carcinoma. Int J Cancer 2009;124:2744-9.
• 22. Ito Y, Yoshida H, Maruo R, et al. 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 2009;56:89-97.
• 23. Kurt B, Yalçın S, Alagöz E, et al. The relationship of the BRAF(V600E) mutation and the established prognostic factors in papillary thyroid carcinomas. Endocr Pathol 2012;23:135-40.
• 24. Marotta V, Guerra A, Zatelli MC, et al. BRAF mutation positive papillary thyroid carcinoma is less advanced when Hashimoto's thyroiditis lymphocytic infiltration is present. Clin Endocrinol (Oxf) 2013;79:733-8.
• 25. Kang DY, Kim KH, Kim JM, et al. High prevalence of RET, RAS, and ERK expression in Hashimoto's thyroiditis and in papillary thyroid carcinoma in the Korean population. Thyroid 2007;17:1031-8.