Journal of Endocrinological Investigation

, Volume 37, Issue 10, pp 1009–1014 | Cite as

BRAF mutation analysis in thyroid nodules with indeterminate cytology: our experience on surgical management of patients with thyroid nodules from an area of borderline iodine deficiency

  • P. Agretti
  • F. Niccolai
  • T. Rago
  • G. De Marco
  • A. Molinaro
  • M. Scutari
  • C. Di Cosmo
  • G. Di Coscio
  • M. Vitale
  • M. Maccheroni
  • P. Vitti
  • M. Tonacchera
Original Article



Fine-needle aspiration (FNA) with cytologic evaluation is the most reliable tool for malignancy prediction in thyroid nodules, but cytologic diagnosis remains indeterminate for 12–18 % of nodules. BRAF V600E mutation has been reported to show a high specificity for malignant thyroid nodules and the use of this marker to refine indeterminate FNA cytology results may be a useful diagnostic adjunctive tool in the pre-operative evaluation of thyroid nodules. The aim of this study was to estimate the prevalence of BRAF exon 15 mutation (V600E) and its clinical value as a diagnostic tool in a series of thyroid nodules with indeterminate cytology from an area of borderline iodine deficiency.

Subjects and methods

One hundred and fifty-three thyroid samples obtained by FNA of thyroid nodules from 151 patients were subjected to the analysis of BRAF V600E mutation by direct sequencing. In the study 54 nodules with indeterminate cytology, 56 benign and 43 malignant thyroid nodules were included.


V600E BRAF gene mutation was demonstrated in 19/43 malignant nodules, in 0/56 benign nodules and in only 1/54 indeterminate nodules that, after histology, turned out to be at a papillary thyroid carcinoma.


The application of BRAF exon 15 analysis showed limitations when applied to discriminate thyroid nodules with indeterminate cytology if wild-type BRAF is found, and there is no role for avoiding diagnostic thyroid surgery.


Thyroid nodules Fine-needle aspiration Follicular proliferation Genetic analysis 



We are grateful to Ministero dell’ Università e della Ricerca Scientifica (MURST) and Ministero della Sanità for funding.

Conflict of interest

The authors declare that they have no actual or potential conflict of interest.

Ethical standards

The study was approved by the local ethical committee and informed consent was obtained from all subjects.


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Copyright information

© Italian Society of Endocrinology (SIE) 2014

Authors and Affiliations

  • P. Agretti
    • 1
  • F. Niccolai
    • 1
  • T. Rago
    • 1
  • G. De Marco
    • 1
  • A. Molinaro
    • 1
  • M. Scutari
    • 1
  • C. Di Cosmo
    • 1
  • G. Di Coscio
    • 2
  • M. Vitale
    • 3
  • M. Maccheroni
    • 1
  • P. Vitti
    • 1
  • M. Tonacchera
    • 1
  1. 1.Department of Clinical and Experimental Medicine, Section of EndocrinologyUniversity of Pisa and University Hospital of PisaPisaItaly
  2. 2.Department of Oncology, Section of CytopathologyUniversity of Pisa and University Hospital of PisaPisaItaly
  3. 3.Department of Medicine and SurgeryUniversity of SalernoSalernoItaly

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