THE ROLE OF BRAF V600E IN THE DEVELOPMENT OF THYROID CANCER PHENOTYPE: A SYSTEMATIC REVIEW
Main Article Content
BRAF V600E mutation in thyroid cancer is of major concern because it is associated with increased tumor aggressiveness through the MAPK pathway activation that affects phenotypic characteristics such as morphology and tissue invasion patterns. The results of studies on the effects of this mutation often vary and are influenced by differences in study design and detection methods. This systematic review aims to clarify the relationship between BRAF V600E and phenotypic characteristics of PTC, as well as identify its clinical implications. This study method was a systematic literature review using the PRISMA method, and there were 8418 journals. After exclusion, 16 articles were found that met the research objectives. Based on the results, it was found that there was a relationship between BRAF V600E and thyroid cancer phenotypes such as female gender, older age at diagnosis, larger tumor size, histological subtypes, especially tall cell, higher nuclear score, capsule, extrathyroid, vascular, nerve invasion, lymph node metastasis, higher clinical stage, recurrence, and lower survival. However, there are other inconsistent studies regarding the association of BRAF V600E with these phenotype characteristics. BRAF V600E mutation significantly affects the phenotypic characteristics of thyroid cancer and is associated with several aggressive characteristics.
Keywords:
BRAF V600E
Thyroid cancer
Phenotype
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22. Al-Masri M, Al-Shobaki T, Al-Najjar H, Iskanderian R, Younis E, Abdallah N, et al. BRAF V600E mutation in papillary thyroid carcinoma: its relation to clinical features and oncologic outcomes in a single cancer centre experience. Endocr Connect. 2021 Dec 1;10(12):1531–7.
2. Jung CK, Bychkov A, Song DE, Kim JH, Zhu Y, Liu Z, et al. Molecular correlates and nuclear features of encapsulated follicular-patterned thyroid neoplasms. Endocrinology and Metabolism. 2021 Feb 1;36(1):123–33.
3. Harahap AS, Subekti I, Panigoro SS, Asmarinah, Lisnawati, Werdhani RA, et al. Developing Models to Predict BRAFV600E and RAS Mutational Status in Papillary Thyroid Carcinoma Using Clinicopathological Features and pERK1/2 Immunohistochemistry Expression. Biomedicines. 2023 Oct 1;11(10).
4. Caronia LM, Phay JE, Shah MH. Role of BRAF in thyroid oncogenesis. Vol. 17, Clinical Cancer Research. 2011. p. 7511–7.
5. Virk RK, Theoharis CGA, Prasad A, Chhieng D, Prasad ML. Morphology predicts BRAFV600E mutation in papillary thyroid carcinoma: An interobserver reproducibility study. Virchows Archiv. 2014 Apr 1;464(4):435–42.
6. Rossi ED, Bizzarro T, Martini M, Capodimonti S, Fadda G, Larocca LM, et al. Morphological parameters able to predict BRAFV600E-mutated malignancies on thyroid fine-needle aspiration cytology: Our institutional experience. Cancer Cytopathol. 2014 Dec 1;122(12):883–91.
7. Zhang Q, Liu SZ, Guan YX, Chen QJ, Zhu QY. Meta-analyses of association between BRAF V600E mutation and clinicopathological features of papillary thyroid carcinoma. Cellular Physiology and Biochemistry. 2016;38(2):763–76.
8. Hong X, Li J, Duan S, You Y. Retrospective study of BRAFV600E mutation and CT features of papillary thyroid carcinoma. PeerJ. 2024;12.
9. Abdulhaleem M, Bandargal S, Pusztaszeri MP, Rajab M, Greenspoon H, Krasner JR, et al. The Impact of BRAF V600E Mutation Allele Frequency on the Histopathological Characteristics of Thyroid Cancer. Cancers (Basel). 2024 Jan 1;16(1).
10. Harahap AS, Subekti I, Panigoro SS, Asmarinah, Lisnawati, Werdhani RA, et al. Profile of BRAFV600E, BRAFK601E, NRAS, HRAS, and KRAS Mutational Status, and Clinicopathological Characteristics of Papillary Thyroid Carcinoma in Indonesian National Referral Hospital. Application of Clinical Genetics. 2023;16:99–110.
11. Bircan R, Sarıkaya Ş, Gul AE, Aydın B, Özçelik M, Çelik M, et al. BRAF V600E mutation in papillary thyroid cancer is correlated with adverse clinicopathological features but not with iodine exposure. Endokrynol Pol. 2019;70(5):401–8.
12. Gąsior-Perczak D, Kowalik A, Walczyk A, Siołek M, Gruszczyński K, Pałyga I, et al. Coexisting Germline CHEK2 and somatic BRAFV600E mutations in papillary thyroid cancer and their association with clinicopathological features and disease course. Cancers (Basel). 2019 Nov 1;11(11).
13. Pessôa-Pereira D, Medeiros MF da S, Lima VMS, Silva JC da, Cerqueira TL de O, Silva IC da, et al. Association between BRAF (V600E) mutation and clinicopathological features of papillary thyroid carcinoma: A brazilian single-centre case series. Arch Endocrinol Metab. 2019 May 1;63(2):97–106.
14. Shi C, Cao J, Shi T, Liang M, Ding C, Lv Y, et al. BRAFV600Emutation, BRAF-activated long non-coding RNA and miR-9 expression in papillary thyroid carcinoma, and their association with clinicopathological features. World J Surg Oncol. 2020 Jun 27;18(1).
15. Xie M, Xu ZX, Dai M, Zhu YY. Correlation Between the Clinicopathological Features of Papillary Thyroid Carcinoma Complicated with Hashimoto’s Thyroiditis, BRAF V600E Gene Mutation, and RET Gene Rearrangement. Journal of the College of Physicians and Surgeons Pakistan. 2024 Apr 1;34(4):445–50.
16. Zhang M, Gu J, Wang W, Wang K, Zheng L, Feng J, et al. Combined expression of the BRAFV600E mutation and PD-L1 in early papillary thyroid carcinoma and its relationship with clinicopathological features and recurrence—a retrospective cohort study. Gland Surg. 2022;11(12):1908–23.
17. Wang Z, Tang P, Hua S, Gao J, Zhang B, Wan H, et al. Genetic and Clinicopathologic Characteristics of Papillary Thyroid Carcinoma in the Chinese Population: High BRAF Mutation Allele Frequency, Multiple Driver Gene Mutations, and RET Fusion May Indicate More Advanced TN Stage. Onco Targets Ther. 2022;15:147–57.
18. Tabriz N, Grone J, Uslar V, Tannapfel A, Weyhe D. BRAF V600E mutation correlates with aggressive clinico-pathological features but does not influence tumor recurrence in papillary thyroid carcinoma—10-year single-center results. Gland Surg. 2020 Dec;9(6):1902–13.
19. Li GY, Tan HL, Chen P, Hu HY, Liu M, Ou-Yang DJ, et al. Predictive factors for level v lymph node metastases in papillary thyroid carcinoma with brafv600e mutation and clinicopathological features. Cancer Manag Res. 2020;12:3371–8.
20. Gao J, Peng Ma X, Sheng Deng F, Jiang L, Dong Jia W, Li M. Associations of the BRAF V600E Mutation and PAQR3 Protein Expression with Papillary Thyroid Carcinoma Clinicopathological Features. Available from: https://doi.org/10.1007/s12253-019-00779-x
21. Bandoh N, Goto T, Kato Y, Kubota A, Sakaue S, Takeda R, et al. BRAF V600E mutation co-existing with oncogenic mutations is associated with aggressive clinicopathologic features and poor prognosis in papillary thyroid carcinoma. Asian J Surg. 2024 Jan 1;47(1):413–9.
22. Al-Masri M, Al-Shobaki T, Al-Najjar H, Iskanderian R, Younis E, Abdallah N, et al. BRAF V600E mutation in papillary thyroid carcinoma: its relation to clinical features and oncologic outcomes in a single cancer centre experience. Endocr Connect. 2021 Dec 1;10(12):1531–7.
