title: MicroRNA expression profiling is a potential diagnostic tool for thyroid cancer.
abstract: BACKGROUND
  Approximately 30% of fine-needle aspiration (FNA) biopsies of thyroid nodules are indeterminate or nondiagnostic. Recent studies suggest microRNA (miRNA, miR) is differentially expressed in malignant tumors and may have a role in carcinogenesis, including thyroid cancer. The authors therefore tested the hypothesis that miRNA expression analysis would identify putative markers that could distinguish benign from malignant thyroid neoplasms that are often indeterminate on FNA biopsy.
  
  
  METHODS
  A miRNA array was used to identify differentially expressed genes (5-fold higher or lower) in pooled normal, malignant, and benign thyroid tissue samples. Real-time quantitative polymerase chain reaction was used to confirm miRNA array expression data in 104 tissue samples (7 normal thyroid, 14 hyperplastic nodule, 12 follicular variant of papillary thyroid cancer, 8 papillary thyroid cancer, 15 follicular adenoma, 12 follicular carcinoma, 12 Hurthle cell adenoma, 20 Hurthle cell carcinoma, and 4 anaplastic carcinoma cases), and 125 indeterminate clinical FNA samples. The diagnostic accuracy of differentially expressed genes was determined by analyzing receiver operating characteristics.
  
  
  RESULTS
  Ten miRNAs showed >5-fold expression difference between benign and malignant thyroid neoplasms on miRNA array analysis. Four of the 10 miRNAs were validated to be significantly differentially expressed between benign and malignant thyroid neoplasms by quantitative polymerase chain reaction (P < .002): miR-100, miR-125b, miR-138, and miR-768-3p were overexpressed in malignant samples of follicular origin (P < .001), and in Hurthle cell carcinoma samples alone (P < .01). Only miR-125b was significantly overexpressed in follicular carcinoma samples (P < .05). The accuracy for distinguishing benign from malignant thyroid neoplasms was 79% overall, 98% for Hurthle cell neoplasms, and 71% for follicular neoplasms. The miR-138 was overexpressed in the FNA samples (P = .04) that were malignant on final pathology with an accuracy of 75%.
  
  
  CONCLUSIONS
  MicroRNA expression differs for normal, benign, and malignant thyroid tissue. Expression analysis of differentially expressed miRNA could help distinguish benign from malignant thyroid neoplasms that are indeterminate on thyroid FNA biopsy.
authors: Department of Surgery, Division of Surgical Oncology and Endocrine Surgery, University University Medical Center Utrecht, The Netherlands. m.r.vriens@umcutrecht.nl
authors: Menno R
authors: MR
authors: Vriens
authors: Julie
authors: J
authors: Weng
authors: Insoo
authors: I
authors: Suh
authors: Nhung
authors: N
authors: Huynh
authors: Marlon A
authors: MA
authors: Guerrero
authors: Wen T
authors: WT
authors: Shen
authors: Quan-Yang
authors: QY
authors: Duh
authors: Orlo H
authors: OH
authors: Clark
authors: Electron
authors: E
authors: Kebebew
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D006801:Humans; D035683:MicroRNAs / Q000032:analysis*; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs