BRAF and NRAS Mutations in Papillary Thyroid Carcinoma and Concordance in BRAF Mutations Between Primary and Corresponding Lymph Node Metastases

Najla Fakhruddin,#1,2Mark Jabbour,#1Michael Novy,3Hani Tamim,4Hisham Bahmad,5Fadi Farhat,6Ghazi Zaatari,1Tarek Aridi,7Gernot Kriegshauser,3Christian Oberkanins,3 and Rami Mahfouz1

1Pathology and Laboratory Medicine Department of American University of Beirut Medical Center, Beirut, Lebanon

2Department of Pathology Hammoud Hospital University Medical Center, Saida, Lebanon

3ViennaLab Diagnostics GmbH, Vienna, Austria

4Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon

5Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon

6Department of Oncology, Hammoud Hospital University Medical Center, Saida, Lebanon

7Faculty of Medicine, American University of Beirut, Beirut, Lebanon

Rami Mahfouz, Email: bl.ude.bua@11mr.

Corresponding author.

#Contributed equally.

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.