BRAF status in сito-morphological diagnosis of thyroid nodules
DOI:
https://doi.org/10.14739/2310-1237.2020.2.212783Keywords:
papillary thyroid, cancer, BRAF V600E mutation, surgical treatment, fine needle aspiration biopsyAbstract
The aim of study – to determine the significance of the BRAF V600E mutation presence in the cytomorphological diagnosis of thyroid nodules.
Materials and methods. The study included 65 patients requiring surgical treatment for thyroid nodular pathology. Material to determine the BRAF V600E mutation was taken by means of a fine needle aspiration biopsy before surgery. The BRAF V600E mutation was detected by real-time PCR analysis.
Results. A pathomorphological study of the removed thyroid nodules showed that all 22 benign nodules were BRAF-negative. Among the 43 papillary thyroid cancer only 20 were BRAF-positive (46.5 %). BRAF mutations were found more often (P < 0.001) in patients with classical and oxyphilic cell papillary thyroid cancer (60 % and 100 %, respectively) than in patients with follicular variant of PTC (6.7 %). Locally invasive tumors were more often BRAF-negative cases (P < 0.05) than non-invasive tumors and amounted to 75.0 % and 37.5 %, respectively. But, when comparing the morphological variant and invasive properties of the tumor, it was found that all cases of the follicular variant of the PC had signs of invasion and were significantly more often observed (P < 0.01) compared with the classical and oxyphilic cell variants. The BRAF V600E mutation was observed both in tumors with metastasis to the regional lymph nodes (55.0 %) and in tumors without metastases (37.5 %), with no significant difference.
Conclusions. The presence of the BRAF V600E mutation is a diagnostic marker for papillary thyroid carcinoma, and its detection confirms the presence of malignancy. BRAF positive carcinomas were in 46.5 % of cases. The combination of BRAF-negative and the cytology of groups V and VI by Bethesda may indicate about a follicular variant of PTC. An increase in the number of molecular genetic markers in the preoperative diagnosis of thyroid cancer can significantly improve the quality of diagnosis and surgical treatment.
References
Ward, E. M., Sherman, R. L., Henley, S. J., Jemal, A., Siegel, D. A., Feuer, E. J., Firth, A. U., Kohler, B. A., Scott, S., Ma, J., Anderson, R. N., Benard, V., & Cronin, K. A. (2019). Annual Report to the Nation on the Status of Cancer, Featuring Cancer in Men and Women Age 20-49 Years. Journal of the National Cancer Institute, 111(12), 1279-1297. https://doi.org/10.1093/jnci/djz106
Haugen, B. R., Alexander, E. K., Bible, K. C., Doherty, G. M., Mandel, S. J., Nikiforov, Y. E., Pacini, F., Randolph, G. W., Sawka, A. M., Schlumberger, M., Schuff, K. G., Sherman, S. I., Sosa, J. A., Steward, D. L., Tuttle, R. M., & Wartofsky, L. (2016). 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, 26(1), 1-133. https://doi.org/10.1089/thy.2015.0020
Cibas, E. S., & Ali, S. Z. (2009). The Bethesda system for reporting thyroid cytopathology. American Journal of Clinical Pathology, 132(5), 658-665. https://doi.org/10.1309/AJCPPHLWMI3JV4LA
Chen, X., Zhou, Q., Wang, F., Zhang, F., Du, H., Zhang, Q., Wu, W., & Gong, X. (2018). Value of BRAF V600E in high-risk thyroid nodules with benign cytology results. American Journal of Neuroradiology, 39(12), 2360-2365. https://doi.org/10.3174/ajnr.A5898
Jinih, M., Foley, N., Osho, O., Houlihan, L., Toor, A. A., Khan, J. Z., Achakzai, A. A., & Redmond, H. P. (2017). BRAFV600E mutation as a predictor of thyroid malignancy in indeterminate nodules: A systematic review and meta-analysis. European Journal of Surgical Oncology, 43(7), 1219-1227. https://doi.org/10.1016/j.ejso.2016.11.003
Nikiforov Y. E. (2017). Role of molecular markers in thyroid nodule management: then and now. Endocrine Practice, 23(8), 979-988. https://doi.org/10.4158/ep171805.ra
Muzza, M., Colombo, C., Pogliaghi, G., Karapanou, O., & Fugazzola, L. (2020). Molecular markers for the classification of cytologically indeterminate thyroid nodules. Journal of Endocrinological Investigation, 43, 703-716 (2020). https://doi.org/10.1007/s40618-019-01164-w
Paschke, R., Cantara, S., Crescenzi, A., Jarzab, B., Musholt, T. J., & Sobrinho Simoes, M. (2017). European Thyroid Association Guidelines regarding Thyroid Nodule Molecular Fine-Needle Aspiration Cytology Diagnostics. European Thyroid Journal, 6(3), 115-129. https://doi.org/10.1159/000468519
Ferrari, S. M., Fallahi, P., Ruffilli, I., Elia, G., Ragusa, F., Paparo, S. R., Baldini, E., Giannini, R., Miccoli, P., Antonelli, A., & Basolo, F. (2018). Molecular testing in the diagnosis of differentiated thyroid carcinomas. Gland Surgery, 7(1), S19-S29. https://doi.org/10.21037/gs.2017.11.07
Pusztaszeri, M. P., Krane, J. F., & Faquin, W. C. (2015). BRAF testing and thyroid FNA. Cancer Cytopathology, 123(12), 689-695. https://doi.org/10.1002/cncy.21614
Beiša, A., Kvietkauskas, M., Beiša, V., Stoškus, M., Ostanevičiūtė, E., Jasiūnas, E., Griškevičius, L., & Strupas, K. (2017). The utility of the Bethesda category and its association with BRAF mutation in the prediction of papillary thyroid cancer stage. Langenbeck’s Archives of Surgery, 402(2), 227-234. https://doi.org/10.1007/s00423-017-1560-2
Sohn, S. Y., Park, W. Y., Shin, H. T., Bae, J. S., Ki, C. S., Oh, Y. L., Kim, S., & Chung, J. H. (2016). Highly Concordant Key Genetic Alterations in Primary Tumors and Matched Distant Metastases in Differentiated Thyroid Cancer. Thyroid, 26(5), 672-682. https://doi.org/10.1089/thy.2015.0527
Zhao, C. K., Zheng, J. Y., Sun, L. P., Xu, R. Y., Wei, Q., & Xu, H. X. (2019). BRAFV600E mutation analysis in fine-needle aspiration cytology specimens for diagnosis of thyroid nodules: The influence of false-positive and false-negative results. Cancer Medicine, 8(12), 5577-5589. https://doi.org/10.1002/cam4.2478
Таrashchenko, Yu. М., Коvalenko, А. E., Оstafiychuk, М. V., Yanchiі, І. R., Меlnyk, М. D., Zelinskaya, G. V., & Naida, Yu. М. (2019). Khirurhichne likuvannia tyreoidnykh vuzliv nevyznachenoi tsytolohichnoi struktury [Surgical treatment of the thyroid nodes of uncertain cytological structure]. Klinichna khirurhiia, 86(5), 59-63. [in Ukrainian]. https://doi.org/10.22141/2224-0721.14.7.2018.148775
Chirayath, S., Pavithran, P., Abraham, N., Nair, V., Bhavani, N., Kumar, H., Menon, U. V., & Menon, A. (2019). Prospective study of bethesda categories III and IV thyroid nodules: Outcomes and predictive value of BRAFV600E mutation. Indian Journal of Endocrinology and Metabolism, 23(3), 278-281. https://doi.org/10.4103/ijem.IJEM-635-18
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