Detection of Circulating BRAF(V600E) in Patients with Papillary Thyroid Carcinoma

J Mol Diagn. 2016 Jan;18(1):100-8. doi: 10.1016/j.jmoldx.2015.08.003. Epub 2015 Nov 26.


BRAF(V600E) is a common mutation in papillary thyroid carcinoma (PTC) correlated with aggressive features. Our objective was to assess the feasibility and accuracy of a novel RNA-based blood assay to identify individuals with a high-risk tumor mutation in patients with PTC. Patients with benign or malignant thyroid disorders were included between September 2013 and July 2014 before either thyroidectomy (n = 62) or treatment of recurrent or metastatic PTC (n = 8). RNA was isolated from peripheral blood lymphocytes and reverse transcribed and followed by two rounds of nested PCR amplification with a restriction digest specific for wild-type BRAF. BRAF(V600E) levels were quantified with standardization curves. Circulating BRAF(V600E) levels were compared with BRAF mutation status from surgical pathologic DNA-based tissue assays. Testing characteristics and receiving-operator curve using tissue results as the gold standard were assessed. Matched blood and tissue assays for BRAF(V600E) were performed on 70 patients with PTC (stages I to IV, n = 48) or other (n = 22) thyroid tumors. Sixty-three percent of PTC patients tested positive for BRAF(V600E) with conventional tissue assays on surgical specimens. The correlation between the RNA-based blood assay and tissue BRAF status was 0.71. PTC patients harbor detectable BRAF(V600E) circulating tumor cells. This blood assay is feasible and has potential as a biomarker for prognosis, surveillance, clinical decision making, and assessment of treatment response to BRAF-targeted therapies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / blood*
  • Biomarkers, Tumor / genetics*
  • Carcinoma / blood*
  • Carcinoma / genetics*
  • Carcinoma / surgery
  • Carcinoma, Papillary
  • Female
  • Humans
  • Lymphocytes / cytology
  • Male
  • Middle Aged
  • Mutation / genetics
  • Proto-Oncogene Proteins B-raf / blood*
  • Proto-Oncogene Proteins B-raf / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thyroid Cancer, Papillary
  • Thyroid Neoplasms / blood*
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / surgery
  • Thyroidectomy


  • Biomarkers, Tumor
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf