A five-gene panel refines differential diagnosis of thyroid nodules

J Clin Lab Anal. 2021 Sep;35(9):e23920. doi: 10.1002/jcla.23920. Epub 2021 Jul 28.

Abstract

Background: Molecular testing for oncogenic mutations in fine-needle aspiration has showed high predictive value in identifying malignant lesions from thyroid nodules with indeterminate cytology.

Methods: To figure out an efficient and economical gene panel for most medical institutions in China, we designed a five-gene panel including BRAF/NRAS/KRAS/HRAS/TERT genes and conducted a retrospective study to evaluate the role of this five-gene diagnostic panel in differential diagnosis of thyroid nodules.

Results: A total of 665 patients with 695 thyroid nodules were investigated in the current study. The fine-needle aspiration biopsy and surgically separated thyroid tissue specimens were harvested to test BRAF, TERT, NRAS, KRAS, and HRAS mutations. We identified 261 mutations in 665 patients, including 177 V600E mutations in BRAF. Three hundred and sixty-nine patients who underwent thyroid surgery after completion of the initial clinical and cytological evaluation were enrolled in the final analysis. The diagnostic sensitivity, specificity, and accuracy of the combination of FNAB cytology and five-gene detection were 74.7%, 93.8%, and 84.8%, respectively. BRAF V600E and five-gene panel could recognize 46.4% and 53.6% of papillary thyroid carcinoma in the patients with cytologically indeterminate nodules.

Conclusion: The five-gene panel can effectively improve the sensitivity, negative predictive value, and accuracy of fine-needle aspiration biopsy cytology, especially in the patients with cytologically indeterminate nodules.

Keywords: BRAF; RAS; cytology; differential diagnosis; thyroid nodules.

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Biopsy, Fine-Needle
  • Diagnosis, Differential
  • GTP Phosphohydrolases / genetics
  • Humans
  • Membrane Proteins / genetics
  • Molecular Diagnostic Techniques
  • Mutation*
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins p21(ras) / genetics
  • ROC Curve
  • Retrospective Studies
  • Telomerase / genetics
  • Thyroid Cancer, Papillary / diagnosis*
  • Thyroid Cancer, Papillary / genetics
  • Thyroid Cancer, Papillary / surgery
  • Thyroid Neoplasms / diagnosis*
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / surgery
  • Thyroid Nodule / diagnosis*
  • Thyroid Nodule / genetics
  • Thyroid Nodule / surgery

Substances

  • Biomarkers, Tumor
  • KRAS protein, human
  • Membrane Proteins
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • TERT protein, human
  • Telomerase
  • GTP Phosphohydrolases
  • NRAS protein, human
  • HRAS protein, human
  • Proto-Oncogene Proteins p21(ras)