title: Three-gene molecular diagnostic model for thyroid cancer.
abstract: BACKGROUND
  The preoperative diagnosis of thyroid nodules primarily depends upon fine needle aspiration (FNA) cytology. However, up to 25% of FNA samples have associated "suspicious or indeterminate", but not diagnostic cytologic reports, resulting in difficulty deciding appropriate clinical management for these patients. We hypothesize that the use of molecular markers as an adjunct to FNA cytology can improve the distinction of benign from malignant nodules that have associated suspicious or indeterminate cytology.
  
  
  METHODS
  Using microarray analysis, we previously identified and reported on 75 genes useful in the distinction of benign versus malignant thyroid nodules. In the present study, we have further validated the expression of 14 of these markers in a large number of thyroid samples by immunohistochemistry (IHC) analysis of 154 thyroid tumors and quantitative real-time RT-PCR (QRT-PCR) analysis of 95 FNA samples. Of the 154 tumors analyzed by IHC, 44 samples (29%) had associated suspicious or indeterminate FNA cytology.
  
  
  RESULTS
  Receiver operating characteristic using three-gene model, (HMGA2, MRC2, and SFN) analysis for the detection of malignant nodules resulted in areas under the curve (AUCs) of≥0.95 (80% sensitivity; 100% specificity) and≥0.84 (71% sensitivity; 84% specificity) for the IHC data in tumors, and QRT-PCR data in FNA samples, respectively.
  
  
  CONCLUSIONS
  Our results suggest that a three-gene model for the cytological diagnosis of indeterminate thyroid nodules is both feasible and promising. Implementation of this as an adjunct to thyroid cytology may significantly impact the clinical management of patients with suspicious or indeterminate thyroid FNA nodules.
authors.affiliation: Endocrine Surgery Section, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA. nprasad1@jhmi.edu
authors.forename: Nijaguna B
authors.initials: NB
authors.lastname: Prasad
authors.forename: Jeanne
authors.initials: J
authors.lastname: Kowalski
authors.forename: Hua-Ling
authors.initials: HL
authors.lastname: Tsai
authors.forename: Kristin
authors.initials: K
authors.lastname: Talbot
authors.forename: Helina
authors.initials: H
authors.lastname: Somervell
authors.forename: Guennadi
authors.initials: G
authors.lastname: Kouniavsky
authors.forename: Yongchun
authors.initials: Y
authors.lastname: Wang
authors.forename: Alan P B
authors.initials: AP
authors.lastname: Dackiw
authors.forename: William H
authors.initials: WH
authors.lastname: Westra
authors.forename: Douglas P
authors.initials: DP
authors.lastname: Clark
authors.forename: Steven K
authors.initials: SK
authors.lastname: Libutti
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Umbricht
authors.forename: Martha A
authors.initials: MA
authors.lastname: Zeiger
mesh_terms: D048948:14-3-3 Proteins / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics*; D044963:Biopsy, Fine-Needle; D016022:Case-Control Studies; D005092:Exonucleases / Q000235:genetics*; D005095:Exoribonucleases; D005819:Genetic Markers; D025743:HMGA2 Protein / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D037241:Mannose-Binding Lectins / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000235:genetics*; D046228:Microarray Analysis; D025202:Molecular Diagnostic Techniques; D011237:Predictive Value of Tests; D060888:Real-Time Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000235:genetics*; D012680:Sensitivity and Specificity; D013964:Thyroid Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D016606:Thyroid Nodule / Q000175:diagnosis / Q000235:genetics / Q000473:pathology
chemical_list: D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D005819:Genetic Markers; D025743:HMGA2 Protein; C404106:MRC2 protein, human; D037241:Mannose-Binding Lectins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D005092:Exonucleases; D005095:Exoribonucleases; C413442:SFN protein, human