title: Comprehensive MicroRNA expression profiling identifies novel markers in follicular variant of papillary thyroid carcinoma.
abstract: BACKGROUND
  Follicular variant of papillary thyroid carcinoma (FVPTC) shares features of papillary (PTC) and follicular (FTC) thyroid carcinomas on a clinical, morphological, and genetic level. MicroRNA (miRNA) deregulation was extensively studied in PTCs and FTCs. However, very limited information is available for FVPTC. The aim of this study was to assess miRNA expression in FVPTC with the most comprehensive miRNA array panel and to correlate it with the clinicopathological data.
  
  
  METHODS
  Forty-four papillary thyroid carcinomas (17 FVPTC, 27 classic PTC) and eight normal thyroid tissue samples were analyzed for expression of 748 miRNAs using Human Microarray Assays on the ABI 7900 platform (Life Technologies, Carlsbad, CA). In addition, an independent set of 61 tumor and normal samples was studied for expression of novel miRNA markers detected in this study.
  
  
  RESULTS
  Overall, the miRNA expression profile demonstrated similar trends between FVPTC and classic PTC. Fourteen miRNAs were deregulated in FVPTC with a fold change of more than five (up/down), including miRNAs known to be upregulated in PTC (miR-146b-3p, -146-5p, -221, -222 and miR-222-5p) and novel miRNAs (miR-375, -551b, 181-2-3p, 99b-3p). However, the levels of miRNA expression were different between these tumor types and some miRNAs were uniquely dysregulated in FVPTC allowing separation of these tumors on the unsupervised hierarchical clustering analysis. Upregulation of novel miR-375 was confirmed in a large independent set of follicular cell derived neoplasms and benign nodules and demonstrated specific upregulation for PTC. Two miRNAs (miR-181a-2-3p, miR-99b-3p) were associated with an adverse outcome in FVPTC patients by a Kaplan-Meier (p < 0.05) and multivariate Cox regression analysis (p < 0.05).
  
  
  CONCLUSIONS
  Despite high similarity in miRNA expression between FVPTC and classic PTC, several miRNAs were uniquely expressed in each tumor type, supporting their histopathologic differences. Highly upregulated miRNA identified in this study (miR-375) can serve as a novel marker of papillary thyroid carcinoma, and miR-181a-2-3p and miR-99b-3p can predict relapse-free survival in patients with FVPTC thus potentially providing important diagnostic and predictive value.
authors: 1 Department of Pathology and Laboratory Medicine, University of Pittsburgh Medical Center , Pittsburgh, Pennsylvania.
authors: Matthias
authors: M
authors: Dettmer
authors: Aurel
authors: A
authors: Perren
authors: Holger
authors: H
authors: Moch
authors: Paul
authors: P
authors: Komminoth
authors: Yuri E
authors: YE
authors: Nikiforov
authors: Marina N
authors: MN
authors: Nikiforova
mesh_terms: D000328:Adult; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D002291:Carcinoma, Papillary; D018265:Carcinoma, Papillary, Follicular / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D015999:Multivariate Analysis; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D000077273:Thyroid Cancer, Papillary; D013961:Thyroid Gland / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D016896:Treatment Outcome
chemical_list: C540933:MIRN375 microRNA, human; C561679:MIRN99 microRNA, human; C540193:MIrn181 microRNA, human; D035683:MicroRNAs