title: A 4-MicroRNA signature can discriminate primary lymphomas from anaplastic carcinomas in thyroid cytology smears.
abstract: BACKGROUND
  Anaplastic thyroid carcinoma (ATC) and primary thyroid lymphoma (PTL) are uncommon tumors of the thyroid gland with several overlapping clinical and pathologic features that may render their differentiation difficult in fine-needle aspiration (FNA) cytology. MicroRNA (miRNA) signatures have been recently reported as useful diagnostic tools applied to cytology specimens.
  
  
  METHODS
  Smears of 23 ATCs, 14 PTLs, and 20 non-neoplastic materials with multinodular goiter (MNG) were retrieved and classified based on their cytologic features and flow cytometric profiles. The ATC-related expression of hsa-miR-26a, hsa-miR-146b, hsa-miR-221, and hsa-miR-222 was quantified using quantitative reverse transcriptase-polymerase chain reaction analysis.
  
  
  RESULTS
  All miRNAs were remarkably up-regulated in ATC samples compared with PTL samples (P < .01). Moreover, expression levels of hsa-miR-146b, hsa-miR-221, and hsa-miR-222 were significantly higher in ATCs than in MNG samples (P < .01). Significant down-regulation of hsa-miR-26a was observed in PTLs compared with MNG samples, whereas hsa-miR-146b was overexpressed. Receiver operating characteristic analysis was used to determine the optimal cutoff for distinguishing ATC from PTL. The estimated receiver operating characteristic thresholds displayed a sensitivity level greater than 0.80 in achieving a diagnosis of PTL, allowing the correct identification of 13 of 14 PTL samples (93%).
  
  
  CONCLUSIONS
  Histotype-specific miRNA signatures can provide new insight into the molecular mechanisms of thyroid carcinogenesis. The tested 4-miRNA signature is a promising diagnostic tool for differentiating ATC from PTL and non-neoplastic MNG, even in the presence of scant material obtained from minimally invasive procedures.
authors: Department of Medicine, Surgical Pathology and Cytopathology Unit, University of Padua, Padua, Italy.
authors: Ambrogio
authors: A
authors: Fassina
authors: Rocco
authors: R
authors: Cappellesso
authors: Francesca
authors: F
authors: Simonato
authors: Maayan
authors: M
authors: Siri
authors: Laura
authors: L
authors: Ventura
authors: Francesca
authors: F
authors: Tosato
authors: Lill-Tove
authors: LT
authors: Busund
authors: Maria Rosa
authors: MR
authors: Pelizzo
authors: Matteo
authors: M
authors: Fassan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D044963:Biopsy, Fine-Needle / Q000379:methods; D015331:Cohort Studies; D003937:Diagnosis, Differential; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006044:Goiter, Nodular / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D008223:Lymphoma / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D035683:MicroRNAs / Q000032:analysis / Q000235:genetics*; D008875:Middle Aged; D012372:ROC Curve; D035583:Rare Diseases; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D012189:Retrospective Studies; D065646:Thyroid Carcinoma, Anaplastic; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D015854:Up-Regulation
chemical_list: D035683:MicroRNAs
keywords: fine-needle cytology; mantel zone lymphoma; microRNAs; primary thyroid lymphoma; thyroid cancer