Abstract
Concordance between mutations in the primary papillary thyroid carcinoma (PTC) and the paired x lymph node metastasis may elucidate the potential role of molecular targeted therapy in advanced stages. BRAF and NRAS mutations in primary PTC (n = 253) with corresponding metastatic lymph node (n = 46) were analyzed utilizing StripAssays (ViennaLab Diagnostics). Statistical analysis was performed using (SPSS, Inc.), version 24.0 with a p-value of <0.05, and concordance via kappa agreement. BRAF mutation frequency in conventional PTC (cPTC): 56.8%, papillary thyroid microcarcinoma (PTMC): 36.5%, PTMC-FV: 2.7% and PTC-FV: 4.1%. NRAS mutation frequency in PTC-FV: 28.6%, PTMC: 28.6%, PTMC-FV: 23.8%, and cPTC: 19.0%. BRAF mutation correlation with older age in cPTC (42.6 versus 33.6) years (p < 0.001) was the only significant clinicopathologic parameter. BRAF mutations were concordant in the primary and its corresponding lymph node deposits in PTC with a kappa of 0.77 (p-value < 0.0001). BRAF mutations are predominant in cPTC and PTMC while NRAS mutations in PTC-FV. BRAF mutation is conserved in metastatic lymph node deposits, thus BRAF is an early mutational pathogenetic driver. Therefore, targeted therapy is potential in recurrent and advanced stage disease.
Highlights
Several studies reported an association of the BRAF mutational status with a number of papillary thyroid carcinoma (PTC) clinicopathologic parameters inclusive of recurrence and worse prognosis[10, 11]
The C228T TERT promoter mutation has been shown to be associated with the BRAFV600E mutation, which was prevalent in the aggressive types of thyroid cancer[19]
We sought to determine the frequencies and types of BRAF and NRAS mutations in a cohort of Lebanese patients and correlate between the findings and the various clinicopathologic features of individual PTC subtypes: conventional PTC, papillary thyroid microcarcinoma (PTMC) defined as tumors measuring ≤1 cm in maximum diameter, follicular variant of PTMC (PTMC-FV) and the follicular variant of PTC (PTC-FV)
Summary
Several studies reported an association of the BRAF mutational status with a number of PTC clinicopathologic parameters inclusive of recurrence and worse prognosis[10, 11]. Alternative studies reported a prediction of lymph node status based on BRAF cytology[15, 16], while Barabaro et al identified no significant association[17]. We aimed in this study to determine the BRAF and NRAS molecular signature concordance rates between the four main different primary PTC subtypes and the corresponding paired metastatic lymph node deposits in order to elucidate the potential clinical implication of selective molecular targeted therapy in advanced stage PTC. We sought to determine the frequencies and types of BRAF and NRAS mutations in a cohort of Lebanese patients and correlate between the findings and the various clinicopathologic features of individual PTC subtypes: conventional PTC (cPTC), papillary thyroid microcarcinoma (PTMC) defined as tumors measuring ≤1 cm in maximum diameter, follicular variant of PTMC (PTMC-FV) and the follicular variant of PTC (PTC-FV)
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