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

Sci Rep. 2017 Jul 5;7(1):4666. doi: 10.1038/s41598-017-04948-3.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Carcinoma, Papillary / genetics
  • Female
  • GTP Phosphohydrolases / genetics*
  • Humans
  • Lymphatic Metastasis / genetics*
  • Male
  • Membrane Proteins / genetics*
  • Middle Aged
  • Mutation*
  • Proto-Oncogene Proteins B-raf / genetics*
  • Retrospective Studies
  • Thyroid Cancer, Papillary / genetics*
  • Thyroid Neoplasms / genetics*
  • Young Adult

Substances

  • Membrane Proteins
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • GTP Phosphohydrolases
  • NRAS protein, human

Supplementary concepts

  • Papillary Thyroid Microcarcinoma