title: Molecular testing for mutations in improving the fine-needle aspiration diagnosis of thyroid nodules.
abstract: BACKGROUND
  Thyroid nodules are common in adults, but only a small fraction of them are malignant. Fine-needle aspiration (FNA) with cytological evaluation is the most reliable tool for cancer diagnosis in thyroid nodules. However, 10-40% of nodules are diagnosed as indeterminate by cytology, making it difficult to optimally manage these patients.
  
  
  OBJECTIVE
  The aim of this study was to establish the feasibility and role of testing for tumor-specific mutations in improving the FNA diagnosis of thyroid nodules.
  
  
  METHODS
  The prospective study included 470 FNA samples of thyroid nodules from 328 patients. At the time of aspiration, a small portion of the material was collected and tested for BRAF, RAS, RET/PTC, and PAX8/PPARgamma mutations. The mutational status was correlated with cytology and either surgical pathology diagnosis or follow-up (mean, 34 months).
  
  
  RESULTS
  A sufficient amount of nucleic acids were isolated in 98% of samples. Thirty-two mutations were found, including 18 BRAF, eight RAS, five RET/PTC, and one PAX8/PPARgamma. The presence of any mutation was a strong indicator of cancer because 31 (97%) of mutation-positive nodules had a malignant diagnosis after surgery. A combination of cytology and molecular testing showed significant improvement in the diagnostic accuracy and allowed better prediction of malignancy in the nodules with indeterminate cytology.
  
  
  CONCLUSIONS
  These results indicate that molecular testing of thyroid nodules for a panel of mutations can be effectively performed in a clinical setting. It enhances the accuracy of FNA cytology and is of particular value for thyroid nodules with indeterminate cytology.
authors.affiliation: Department of Pathology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA. nikiforovye@upmc.edu
authors.forename: Yuri E
authors.initials: YE
authors.lastname: Nikiforov
authors.forename: David L
authors.initials: DL
authors.lastname: Steward
authors.forename: Toni M
authors.initials: TM
authors.lastname: Robinson-Smith
authors.forename: Bryan R
authors.initials: BR
authors.lastname: Haugen
authors.forename: Joshua P
authors.initials: JP
authors.lastname: Klopper
authors.forename: Zhaowen
authors.initials: Z
authors.lastname: Zhu
authors.forename: James A
authors.initials: JA
authors.lastname: Fagin
authors.forename: Mercedes
authors.initials: M
authors.lastname: Falciglia
authors.forename: Katherine
authors.initials: K
authors.lastname: Weber
authors.forename: Marina N
authors.initials: MN
authors.lastname: Nikiforova