Open AccessBRAF and NRAS Mutations in Papillary Thyroid Carcinoma and Concordance in BRAF Mutations Between Primary and Corresponding Lymph Node Metastases
Author(s) -
Najla Fakhruddin,
Mark Jabbour,
Michael Novy,
Hani Tamim,
Hisham F. Bahmad,
Fadi Farhat,
Ghazi Zaatari,
Tarek Aridi,
Gernot Kriegshäuser,
Christian Oberkanins,
Rami Mahfouz
Publication year - 2017
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/s41598-017-04948-3
Subject(s) - neuroblastoma ras viral oncogene homolog , thyroid carcinoma , concordance , medicine , lymph node , mutation , oncology , carcinoma , mutation frequency , thyroid cancer , cancer research , pathology , thyroid , cancer , gene , biology , genetics , kras , colorectal cancer
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.