title: MicroRNA expression array identifies novel diagnostic markers for conventional and oncocytic follicular thyroid carcinomas.
abstract: OBJECTIVE
  The most difficult thyroid tumors to be diagnosed by cytology and histology are conventional follicular carcinomas (cFTCs) and oncocytic follicular carcinomas (oFTCs). Several microRNAs (miRNAs) have been previously found to be consistently deregulated in papillary thyroid carcinomas; however, very limited information is available for cFTC and oFTC. The aim of this study was to explore miRNA deregulation and find candidate miRNA markers for follicular carcinomas that can be used diagnostically.
  
  
  METHODS
  Thirty-eight follicular thyroid carcinomas (21 cFTCs, 17 oFTCs) and 10 normal thyroid tissue samples were studied for expression of 381 miRNAs using human microarray assays. Expression of deregulated miRNAs was confirmed by individual RT-PCR assays in all samples. In addition, 11 follicular adenomas, two hyperplastic nodules (HNs), and 19 fine-needle aspiration samples were studied for expression of novel miRNA markers detected in this study.
  
  
  RESULTS
  The unsupervised hierarchical clustering analysis demonstrated individual clusters for cFTC and oFTC, indicating the difference in miRNA expression between these tumor types. Both cFTCs and oFTCs showed an up-regulation of miR-182/-183/-221/-222/-125a-3p and a down-regulation of miR-542-5p/-574-3p/-455/-199a. Novel miRNA (miR-885-5p) was found to be strongly up-regulated (>40-fold) in oFTCs but not in cFTCs, follicular adenomas, and HNs. The classification and regression tree algorithm applied to fine-needle aspiration samples demonstrated that three dysregulated miRNAs (miR-885-5p/-221/-574-3p) allowed distinguishing follicular thyroid carcinomas from benign HNs with high accuracy.
  
  
  CONCLUSIONS
  In this study we demonstrate that different histopathological types of follicular thyroid carcinomas have distinct miRNA expression profiles. MiR-885-5p is highly up-regulated in oncocytic follicular carcinomas and may serve as a diagnostic marker for these tumors. A small set of deregulated miRNAs allows for an accurate discrimination between follicular carcinomas and hyperplastic nodules and can be used diagnostically in fine-needle aspiration biopsies.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: Matthias
authors.initials: M
authors.lastname: Dettmer
authors.forename: Alexander
authors.initials: A
authors.lastname: Vogetseder
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Durso
authors.forename: Holger
authors.initials: H
authors.lastname: Moch
authors.forename: Paul
authors.initials: P
authors.lastname: Komminoth
authors.forename: Aurel
authors.initials: A
authors.lastname: Perren
authors.forename: Yuri E
authors.initials: YE
authors.lastname: Nikiforov
authors.forename: Marina N
authors.initials: MN
authors.lastname: Nikiforova
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D018249:Adenoma, Oxyphilic; D000465:Algorithms; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D044963:Biopsy, Fine-Needle; D002277:Carcinoma / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D002291:Carcinoma, Papillary; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000032:analysis / Q000235:genetics*; D046228:Microarray Analysis; D024862:Oxyphil Cells / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D054928:Validation Studies as Topic
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs