BRAFV600E Mutation in Papillary Carcinoma Thyroid
Abstract
Background: Thyroid malignancies comprise 1 % of total human malignancies, Papillary Thyroid Carcinoma (PTC) is the most common malignant tumour of thyroid cancers. It is estimated that 80 % of thyroid malignancies are comprised of papillary carcinoma thyroid, which shows increased incidence in women. The most important etiology of PTC is mutation of RET/RAS/BRAF which activates MAPK signaling pathway. The BRAF V600E activating point mutation appears to be highly specific for PTC. Methods: It is cross sectional study of 56 cases studied in the Government Medical college, Thiruvananthapuram, Kerala. Consecutive cases of histo-pathologically proven cases were selected and Immunohistochemical (IHC) studies for BRAFV600E were conducted, and results were recorded. Result: Our study showed female preponderance and equal distribution of cases above and below 45 years of age. Size of the primary tumour was more than 1cm for majority of cases. In our study out of 56 cases studied 45 patients showed BRAFV600E expression comprising of 80% positivity. A 44% of the total cases studied showed lymph node metastasis. Conclusion: We conclude in our study that BRAFV600E mutation is most common mutation in primary PTC patients. BRAFV600E expression most seen in elderly patients and shows strong association with lymph node metastasis. IHC assay is a reliable method to detect BRAFV600E mutation in PTC and can be used as alternative to molecular methods on routine practiceReferences
Mingzhao Xing, BRAF Mutation in Papillary Thyroid Cancer: Pathogenic Role, Molecular Bases, and Clinical Implications, Endocrine Reviews, Volume 28, Issue 7, 1 December 2007, Pages 742–762,
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 Nov;88(11):5399–404.
Namba H, Nakashima M, Hayashi T, et al. Clinical implication of hot spot BRAF mutation, V599E, in papillary thyroid cancers.The Journal of Clinical Endocrinology Metabolism, volume 88,issue 9, 1 september 2003; 4393–7.
Kaliszewski K, Diakowska D, Strutynska-Karpinska M, Rzeszutko M, Grzegrzolka J, Dziegiel P, et al. Expression of cytokeratin-19 (CK19) in the classical subtype of papillary thyroid carcinoma: The experience ofone center in the Silesian region. Folia Histochem Cytobiol.2016;54(4):193-201
Ito Y, Miyauchi A. Prognostic factors of papillary and follicular carcinomas in Japan based on data of Kuma Hospital. Journal of Thyroid Research. 2012; 2012:973497.
Sak SD. Variants of papillary thyroid carcinoma: Multiple faces of a familiar tumor. Turk Patoloji Derg. 2015;31:34–47.
Garnett MJ & Marais R 2004 Guilty as charged: BRAF is a human oncogene. Cancer Cell; 6: 313–319
Nikiforova MN, Kimura ET, Gandhi M, Biddinger PW, Knauf JA, Basolo F, 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;88:5399 –5404
Nakamura N, Carney JA, Jin L, Kajita S, Pallares J, Zhang H, et al. RASSF1A and NORE1A methylation and BRAFV600E mutations in thyroid tumors. Lab Invest.2005 ;85: 1065–75.
Trovisco V, Vieira de Castro I, Soares P, et al. BRAF mutations are associated with some histological types of papillary thyroid carcinoma. J Pathol 2004;202:247–51.
Kim KH, Kang DW, Kim SH, et al. Mutations of the BRAF gene in papillary thyroid carcinoma in a Korean population. Yonsei Med J 2004;45:818–21.
Koperek O, Kornauth C, Capper D, Berghoff AS, Asari R, Niederle B, Von Deimling A, Birner P, Preusser M. Immunohistochemical detection of the BRAF V600E-mutated protein in papillary thyroid carcinoma. The American journal of surgical pathology. 2012 Jun 1;36(6):844-50.
Ghossein RA, Katabi N, Fagin JA. Immunohistochemical detection of mutated BRAF V600E supports the clonal origin of BRAF-induced thyroid cancers along the spectrum of disease progression. The Journal of Clinical Endocrinology & Metabolism. 2013 Aug 1;98(8):E1414-21.
Czarniecka A, Oczko-Wojciechowska M, Barczyński M. BRAF V600E mutation in prognostication of papillary thyroid cancer (PTC) recurrence. Gland surgery. 2016 Oct;5(5):495.
Liu X, Yan K, Lin X, Zhao L, An W, Wang C, Liu X. The association between BRAF V600E mutation and pathological features in PTC. European archives of oto-rhino-laryngology. 2014 Nov;271(11):3041-52.
Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, et al .Mutations of the BRAF gene in human cancer. Nature 2000 ; 417:949 –954
Wan PT, Garnett MJ, Roe SM, Lee S, Niculescu-Duvaz D, Good VM, et al Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF. Cell .2004 ;116(6):855– 867.
Mercer KE, Pritchard CA . Raf proteins and cancer: B-Raf is identified as a mutational target. Biochim Biophys Acta.2003; 1653:25– 40
Garnett MJ, Marais R . Guilty as charged: B-RAF is a human oncogene. Cancer Cell. 2004; 6:313–9
Xing M. BRAF mutation in papillary thyroid cancer: pathogenic role, molecular bases, and clinical implications. Endocr Rev 2007; 28(7):742-62.
Jin ,T . J. Sebo , Nakamura N, Qian X, Oliveira A, Majerus JA, et al. “BRAF mutation analysis in fine needle aspiration (FNA) cytology of the thyroid” Diagnostic Molecular Pathology 2006: 15:136 –143.
Xing M, Westra WH, Tufano RP, Cohen Y, Rosenbaum E, Rhoden KJ, et al. BRAF mutation predicts a poorer clinical prognosis for papillary thyroid cancer. J Clinl Endocrinolo and Metab. 2005; 90 :6373–9.
Kebebew E, Weng J, Bauer J, Ranvier G, Clark OH, Duh QY, et al. The prevalence and prognostic value of BRAF mutation in thyroid cancer. Ann Surg . 2007; 246:466 – 471.
Lupi C, Giannini R, Ugolini C, Proietti A, Berti P, Minuto M, et al . Association of BRAF V600E mutation with poor clinicopathologic outcomes in 500 consecutive cases of papillary thyroid carcinoma. J Clin Endocrinol Metab .2007;92:4085– 4090
Kimura ET, Nikiforova MN, Zhu Z, Knauf JA, Nikiforov YE, Fagin JA. High prevalence of BRAF mutations in thyroid cancer: genetic evidence for constitutive activation of the RET/PTC-RAS-BRAF signaling pathway in papillary thyroid carcinoma. Cancer research. 2003 Apr 1;63(7):1454-7.
Melck AL, Yip L, Carty SE. The utility of BRAF testing in the management of papillary thyroid cancer. Oncologist.2010;15:1285-1293.
Lombardi CP, Bellantone R, De Crea C, Paladino NC, Fadda G,Salvatori M, Raffaelli M. Papillary thyroid microcarcinoma:extrathyroidal extension, lymph node metastases, and risk factors for recurrence in a high prevalence of goiter area. World J Surg.2010;34:1214-1221.
Enewold L, Zhu K, Ron E, Marrogi AJ, Stojadinovic A, Peoples GE, et al. Rising thyroid cancer incidence in the United States by demographic and tumor characteristics, 1980-2005. Cancer Epidemiol Biomarkers Prev. 2009;18(3):784-91.
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