title: Development of a microRNA-based molecular assay for the detection of papillary thyroid carcinoma in aspiration biopsy samples.
abstract: BACKGROUND
  Although thyroid nodules are common and diagnosed in over 5% of the adult population, only 5% harbor malignancy. Patients with clinically suspicious thyroid nodules need to undergo fine-needle aspiration biopsy (FNAB). The main limitation of FNAB remains indeterminate cytopathology. Only 20%-30% of the indeterminate nodules harbor malignancy, and therefore up to 80% of patients undergo unnecessary thyroidectomy. The aim of this study was to identify and validate a panel of microRNAs (miRNAs) that could serve as a platform for an FNAB-based diagnostic for thyroid neoplasms.
  
  
  METHODS
  The study population included 27 consecutive patients undergoing total thyroidectomy for FNAB-based papillary thyroid cancer (n = 20) and benign disorders (n = 7). Aspiration biopsy was performed from the index lesion and from the opposite lobe normal tissue in all study patients at the time of operation. RNA was extracted from all aspiration biopsy samples. Quantitative polymerase chain reaction on a panel of previously selected miRNAs was performed. Polymerase chain reaction results were compared with final histopathology. miRNA from tumor tissues was amplified using the highest value of each miRNA expression in normal tissue as a threshold for malignancy detection.
  
  
  RESULTS
  Diagnostic characteristics were most favorable for mir-221 in differentiating benign from malignant thyroid pathology. mir-221 was overexpressed in 19 patients (p < 0.0001) with a sensitive yield of 95%. Specificity, negative and positive predictive value, and accuracy of the miRNA panel were 100%, 96%, 100%, and 98%, respectively.
  
  
  CONCLUSIONS
  miRNA quantification for differential diagnosis of thyroid neoplasms within aspiration biopsy samples is feasible and may improve the accuracy of FNAB cytology.
authors.affiliation: Department of Surgery, Hadassah-Hebrew University Medical Center , Mount Scopus, Jerusalem, Israel.
authors.forename: Haggi
authors.initials: H
authors.lastname: Mazeh
authors.forename: Ido
authors.initials: I
authors.lastname: Mizrahi
authors.forename: David
authors.initials: D
authors.lastname: Halle
authors.forename: Nadia
authors.initials: N
authors.lastname: Ilyayev
authors.forename: Alexander
authors.initials: A
authors.lastname: Stojadinovic
authors.forename: Barry
authors.initials: B
authors.lastname: Trink
authors.forename: Stella
authors.initials: S
authors.lastname: Mitrani-Rosenbaum
authors.forename: Marina
authors.initials: M
authors.lastname: Roistacher
authors.forename: Ilana
authors.initials: I
authors.lastname: Ariel
authors.forename: Ahmed
authors.initials: A
authors.lastname: Eid
authors.forename: Herbert R
authors.initials: HR
authors.lastname: Freund
authors.forename: Aviram
authors.initials: A
authors.lastname: Nissan
mesh_terms: D000328:Adult; D000368:Aged; D044963:Biopsy, Fine-Needle; D002277:Carcinoma; D002291:Carcinoma, Papillary; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D011237:Predictive Value of Tests; D012334:RNA, Neoplasm / Q000235:genetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology
chemical_list: D035683:MicroRNAs; D012334:RNA, Neoplasm