title: Digital gene expression profiling of a series of cytologically indeterminate thyroid nodules.
abstract: BACKGROUND
  Fine-needle aspiration cytology (FNAC) has been widely accepted as the most crucial step in the preoperative assessment of thyroid nodules. Testing for the expression of specific genes should improve the accuracy of FNAC diagnosis, especially when it is performed in samples with indeterminate cytology.
  
  
  METHODS
  In total, 69 consecutive FNACs that had both cytologic and histologic diagnoses were collected, and expression levels of 34 genes were determined in RNA extracted from FNAC cells by using a custom digital mRNA counting assay. A supervised k-nearest neighbor (K-nn) learning approach was used to build a 2-class prediction model based on a subset of 27 benign and 26 malignant FNAC samples. Then, the K-nn models were used to classify the 16 indeterminate FNAC samples.
  
  
  RESULTS
  Malignant and benign thyroid nodules had different gene expression profiles. The K-nn approach was able to correctly classify 10 FNAC samples as benign, whereas only 1 sample was grouped in the malignant class. Two malignant FNAC samples were incorrectly classified as benign, and 3 of 16 samples were unclassified.
  
  
  CONCLUSIONS
  Although the current data will require further confirmation in a larger number of cases, the preliminary results indicate that testing for specific gene expression appears to be useful for distinguishing between benign and malignant lesions. The results from this study indicate that, in indeterminate FNAC samples, testing for cancer-specific gene expression signatures, together with mutational analyses, could improve diagnostic accuracy for patients with thyroid nodules.
authors.affiliation: Department of Surgical, Medical, and Molecular Pathology and Critical Care, University of Pisa, Pisa, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Giannini
authors.affiliation: Department of Anatomic Pathology, Hospital of Pisa, Pisa, Italy.
authors.forename: Liborio
authors.initials: L
authors.lastname: Torregrossa
authors.affiliation: Diatech Pharmacogenetics srl, Jesi, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Gottardi
authors.affiliation: Department of Surgical, Medical, and Molecular Pathology and Critical Care, University of Pisa, Pisa, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Fregoli
authors.affiliation: Department of Surgical, Medical, and Molecular Pathology and Critical Care, University of Pisa, Pisa, Italy.
authors.forename: Nicla
authors.initials: N
authors.lastname: Borrelli
authors.affiliation: Diatech Pharmacogenetics srl, Jesi, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Savino
authors.affiliation: Department of Surgical, Medical, and Molecular Pathology and Critical Care, University of Pisa, Pisa, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Macerola
authors.affiliation: Department of Experimental and Clinical Medicine, University of Pisa, Pisa, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Vitti
authors.affiliation: Department of Surgical, Medical, and Molecular Pathology and Critical Care, University of Pisa, Pisa, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Miccoli
authors.affiliation: Department of Surgical, Medical, and Molecular Pathology and Critical Care, University of Pisa, Pisa, Italy.
authors.forename: Fulvio
authors.initials: F
authors.lastname: Basolo
mesh_terms: D000328:Adult; D001707:Biopsy, Needle; D015331:Cohort Studies; D003581:Cytodiagnosis / Q000379:methods; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D016606:Thyroid Nodule / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D013965:Thyroidectomy / Q000379:methods
chemical_list: D012333:RNA, Messenger
keywords: fine-needle aspiration cytology; gene expression profiling; messenger RNA signature; thyroid cancer; thyroid nodule