title: Genetic markers to discriminate benign and malignant thyroid nodules with undetermined cytology in an area of borderline iodine deficiency.
abstract: BACKGROUND
  Fine needle aspiration (FNA) with cytologic evaluation is the most reliable tool for malignancy prediction in thyroid nodules, but cytologic diagnosis remains undetermined for 20% of nodules.
  
  
  OBJECTIVE
  We investigated the diagnostic potential of a set of 6 marker genes to distinguish benign and malignant thyroid nodules.
  
  
  METHODS
  The prospective study included 153 thyroid samples obtained by FNA of thyroid nodules from 151 patients (56 benign, 43 malignant, and 54 nodules with undetermined cytology). Gene expression was evaluated by quantitative realtime PCR and statistical analysis of data was performed. All samples were analyzed for V600E BRAF mutation.
  
  
  RESULTS
  A decrease in TTF3 and HGD1 expression was observed in malignant nodules with respect to benign ones, while an increase in PLAB expression was demonstrated in these nodules. The decision model was valid for 88 of 99 cases of benign and malignant nodules, with a total of 11 false positive or negative predictions. The obtained malignant/benign phenotype prediction was also valid for 37 of 54 cases of nodules with undetermined cytology with a total of 8 false positive and 9 false negative predictions. V600E BRAF gene mutation was demonstrated in 19/43 malignant nodules, in 0/56 benign nodules, and in 1/54 undetermined nodules.
  
  
  CONCLUSIONS
  The expression profiles of genes (TFF3, HGD1, and PLAB) allowed a good prediction for the differentiation of benign thyroid lesions and thyroid cancer starting from cells of FNA; however, this assay showed limitations when applied to discriminate thyroid nodules with undetermined cytology.
authors: Department of Endocrinology, Research Center of Excellence AmbiSEN, University of Pisa, Pisa, Italy. mtonacchera@hotmail.com
authors: M
authors: M
authors: Tonacchera
authors: P
authors: P
authors: Agretti
authors: T
authors: T
authors: Rago
authors: G
authors: G
authors: De Marco
authors: F
authors: F
authors: Niccolai
authors: A
authors: A
authors: Molinaro
authors: M
authors: M
authors: Scutari
authors: A
authors: A
authors: Candelieri
authors: D
authors: D
authors: Conforti
authors: R
authors: R
authors: Musmanno
authors: G
authors: G
authors: Di Coscio
authors: F
authors: F
authors: Basolo
authors: P
authors: P
authors: Iacconi
authors: P
authors: P
authors: Miccoli
authors: A
authors: A
authors: Pinchera
authors: P
authors: P
authors: Vitti
mesh_terms: D044963:Biopsy, Fine-Needle; D003581:Cytodiagnosis; D003584:Cytological Techniques; D005260:Female; D005819:Genetic Markers; D006801:Humans; D007455:Iodine / Q000172:deficiency*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012372:ROC Curve; D013959:Thyroid Diseases / Q000145:classification* / Q000175:diagnosis* / Q000235:genetics
chemical_list: D005819:Genetic Markers; D007455:Iodine