Reduction of false-negative papillary thyroid carcinomas by the routine analysis of BRAF(T1799A) mutation on fine-needle aspiration biopsy specimens: a prospective study of 814 thyroid FNAB patients

Ann Surg. 2012 May;255(5):986-92. doi: 10.1097/SLA.0b013e31824e8d70.

Abstract

Objectives: To evaluate prospectively the usefulness of the routine determination of BRAF(T1799A) mutation on thyroid fine-needle aspiration biopsy (FNAB) to detect cytopathology false negative papillary thyroid carcinomas (PTC) and, therefore, as a tool to improve the sensitivity of the preoperative cytopathological diagnosis of PTC in thyroid nodules.

Background: FNAB is the most reliable diagnostic test to discriminate between malignant and benign thyroid nodules, but nondiagnostic results remain a clinical management dilemma. BRAF(T1799A) mutation is the most prevalent genetic alteration in thyroid cancers and is specific for PTC, characteristics that make it the most potentially helpful genetic tool to improve the diagnostic accuracy of FNAB.

Methods: An exhaustive recruitment of all patients subjected to thyroid FNAB in our institution during 4 years was performed. BRAF(T1799A) mutation was determined on thyroid FNAB specimens by PCR and restriction fragment length polymorphism, plus direct sequencing in positive samples.

Results: BRAF(T1799A) mutation on FNAB detected 47.2% (17/36) of PTC cases. It confirmed preoperatively 45.5% (5/11) of the PTC cases in the indeterminate category and decreased the rate of cytopathology false-negatives in 33.3% (6/18), improving the combined (BRAF(T1799A) mutation + cytopathological analysis) sensitivity of the detection of PTC on FNAB in 16.7%.

Conclusions: BRAF(T1799A) mutation improves the diagnosis of PTC on FNAB, mainly because of the detection of cytopathology false-negatives, and it can be helpful in the routine analysis of thyroid nodules, especially in clinical settings with moderate sensitivity to detect PTC on FNAB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biopsy, Fine-Needle
  • Carcinoma, Papillary / genetics*
  • Carcinoma, Papillary / pathology*
  • DNA, Neoplasm / analysis
  • DNA, Neoplasm / isolation & purification
  • False Negative Reactions
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Prospective Studies
  • Proto-Oncogene Proteins B-raf / genetics*
  • Sensitivity and Specificity
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / pathology*
  • Young Adult

Substances

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