title: Multicentre validation of a microRNA-based assay for diagnosing indeterminate thyroid nodules utilising fine needle aspirate smears.
abstract: OBJECTIVE
  The distinction between benign and malignant thyroid nodules has important therapeutic implications. Our objective was to develop an assay that could classify indeterminate thyroid nodules as benign or suspicious, using routinely prepared fine needle aspirate (FNA) cytology smears.
  
  
  METHODS
  A training set of 375 FNA smears was used to develop the microRNA-based assay, which was validated using a blinded, multicentre, retrospective cohort of 201 smears. Final diagnosis of the validation samples was determined based on corresponding surgical specimens, reviewed by the contributing institute pathologist and two independent pathologists. Validation samples were from adult patients (≥18 years) with nodule size >0.5 cm, and a final diagnosis confirmed by at least one of the two blinded, independent pathologists. The developed assay, RosettaGX Reveal, differentiates benign from malignant thyroid nodules, using quantitative RT-PCR.
  
  
  RESULTS
  Test performance on the 189 samples that passed quality control: negative predictive value: 91% (95% CI 84% to 96%); sensitivity: 85% (CI 74% to 93%); specificity: 72% (CI 63% to 79%). Performance for cases in which all three reviewing pathologists were in agreement regarding the final diagnosis (n=150): negative predictive value: 99% (CI 94% to 100%); sensitivity: 98% (CI 87% to 100%); specificity: 78% (CI 69% to 85%).
  
  
  CONCLUSIONS
  A novel assay utilising microRNA expression in cytology smears was developed. The assay distinguishes benign from malignant thyroid nodules using a single FNA stained smear, and does not require fresh tissue or special collection and shipment conditions. This assay offers a valuable tool for the preoperative classification of thyroid samples with indeterminate cytology.
authors: Rosetta Genomics Ltd, Rehovot, Israel.
authors: Gila
authors: G
authors: Lithwick-Yanai
authors: Rosetta Genomics Ltd, Rehovot, Israel.
authors: Nir
authors: N
authors: Dromi
authors: Pathology Institute, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel.|The Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors: Alexander
authors: A
authors: Shtabsky
authors: The Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.|Pathology Institute, Rabin Medical Center, Petach Tikva, Israel.
authors: Sara
authors: S
authors: Morgenstern
authors: The Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.|Pathology Institute, Rabin Medical Center, Petach Tikva, Israel.
authors: Yulia
authors: Y
authors: Strenov
authors: The Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.|Pathology Institute, Rabin Medical Center, Petach Tikva, Israel.
authors: Meora
authors: M
authors: Feinmesser
authors: The Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.|Pathology Institute, Meir Medical Center, Kfar Saba, Israel.
authors: Vladimir
authors: V
authors: Kravtsov
authors: H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
authors: Marino E
authors: ME
authors: Leon
authors: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.
authors: Marián
authors: M
authors: Hajdúch
authors: The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors: Syed Z
authors: SZ
authors: Ali
authors: The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors: Christopher J
authors: CJ
authors: VandenBussche
authors: Temple University Hospital, Philadelphia, Pennsylvania, USA.|Cooper University Hospital, Cooper Medical School of Rowan University at Camden, New Jersey, USA.
authors: Xinmin
authors: X
authors: Zhang
authors: Pathology Institute, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel.|The Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors: Leonor
authors: L
authors: Leider-Trejo
authors: Pathology Institute, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors: Asia
authors: A
authors: Zubkov
authors: National Centre of Clinical and Morphological Diagnostics, St Petersburg, Russia.
authors: Sergey
authors: S
authors: Vorobyov
authors: Rosetta Genomics Ltd, Rehovot, Israel.
authors: Michal
authors: M
authors: Kushnir
authors: Rosetta Genomics Ltd, Rehovot, Israel.|Geha Mental Health Center, Petach Tikva, Israel.
authors: Yaron
authors: Y
authors: Goren
authors: Rosetta Genomics Ltd, Rehovot, Israel.
authors: Sarit
authors: S
authors: Tabak
authors: Rosetta Genomics Ltd, Rehovot, Israel.
authors: Etti
authors: E
authors: Kadosh
authors: Rosetta Genomics Inc, Philadelphia, Pennsylvania, USA.
authors: Hila
authors: H
authors: Benjamin
authors: Rosetta Genomics Ltd, Rehovot, Israel.
authors: Temima
authors: T
authors: Schnitzer-Perlman
authors: Rosetta Genomics Ltd, Rehovot, Israel.
authors: Hagai
authors: H
authors: Marmor
authors: Rosetta Genomics Ltd, Rehovot, Israel.
authors: Maria
authors: M
authors: Motin
authors: Rosetta Genomics Ltd, Rehovot, Israel.
authors: Danit
authors: D
authors: Lebanony
authors: Rosetta Genomics Ltd, Rehovot, Israel.
authors: Sharon
authors: S
authors: Kredo-Russo
authors: Rosetta Genomics Inc, Philadelphia, Pennsylvania, USA.
authors: Heather
authors: H
authors: Mitchell
authors: Rosetta Genomics Inc, Philadelphia, Pennsylvania, USA.
authors: Melissa
authors: M
authors: Noller
authors: Rosetta Genomics Inc, Philadelphia, Pennsylvania, USA.
authors: Alexis
authors: A
authors: Smith
authors: Rosetta Genomics Inc, Philadelphia, Pennsylvania, USA.
authors: Olivia
authors: O
authors: Dattner
authors: Rosetta Genomics Inc, Philadelphia, Pennsylvania, USA.
authors: Karin
authors: K
authors: Ashkenazi
authors: Rosetta Genomics Inc, Philadelphia, Pennsylvania, USA.
authors: Mats
authors: M
authors: Sanden
authors: Rosetta Genomics Inc, Philadelphia, Pennsylvania, USA.
authors: Kenneth A
authors: KA
authors: Berlin
authors: Rosetta Genomics Ltd, Rehovot, Israel.
authors: Dganit
authors: D
authors: Bar
authors: Rosetta Genomics Ltd, Rehovot, Israel.
authors: Eti
authors: E
authors: Meiri
mesh_terms: D044963:Biopsy, Fine-Needle; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D015588:Observer Variation; D011237:Predictive Value of Tests; D013964:Thyroid Neoplasms / Q000175:diagnosis*; D016606:Thyroid Nodule / Q000175:diagnosis*
chemical_list: D035683:MicroRNAs
keywords: DIAGNOSTICS; LABORATORY TESTS; MOLECULAR ONCOLOGY; THYROID; THYROID CANCER