BRAFV600E mutation analysis in fine-needle aspiration cytology specimens for evaluation of thyroid nodule: a large series in a BRAFV600E-prevalent population

J Clin Endocrinol Metab. 2010 Aug;95(8):3693-700. doi: 10.1210/jc.2009-2795. Epub 2010 May 25.

Abstract

Background: The BRAFV600E mutation is highly specific to papillary thyroid carcinoma. A test for this mutation may increase the diagnostic accuracy of fine-needle aspiration cytology (FNAC), especially in a BRAFV600E mutation-prevalent population.

Methods: This prospective study enrolled 1074 patients with thyroid nodules who underwent both FNAC and BRAFV600E mutation analysis by dual-priming oligonucleotide (DPO)-based multiplex PCR in FNA specimens.

Results: The ancillary test for BRAFV600E significantly improved the sensitivity of FNA procedure, from 67.5% with FNAC alone to 89.6% with FNAC and the DPO-based multiplex PCR analysis combined. Diagnostic accuracy increased from 90.9 to 96.6%. Nine cases of papillary thyroid carcinoma were detected only by BRAFV600E mutation analysis. Unexpectedly, the preoperative DPO-based multiplex PCR produced five false-positive results, which surgery showed to represent benign nodules.

Conclusions: Molecular testing for the BRAFV600E mutation in FNA thyroid nodule specimens increases diagnostic value when applied in a BRAFV600E mutation-prevalent population. However, when using this potentially powerful technique, we must consider both its strengths and its weaknesses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biopsy, Fine-Needle
  • Carcinoma, Papillary / diagnosis
  • Carcinoma, Papillary / genetics*
  • DNA Mutational Analysis
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Polymerase Chain Reaction
  • Proto-Oncogene Proteins B-raf / genetics*
  • Sensitivity and Specificity
  • Thyroid Neoplasms / diagnosis
  • Thyroid Neoplasms / genetics*
  • Thyroid Nodule / diagnosis
  • Thyroid Nodule / genetics*

Substances

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