MicroRNA profile of poorly differentiated thyroid carcinomas: new diagnostic and prognostic insights.
The diagnosis of conventional and oncocytic poorly differentiated (oPD) thyroid carcinomas is difficult. The aim of this study is to characterise their largely unknown miRNA expression profile and to compare it with well-differentiated thyroid tumours, as well as to identify miRNAs which could potentially serve as diagnostic and prognostic markers. A total of 14 poorly differentiated (PD), 13 oPD, 72 well-differentiated thyroid carcinomas and eight normal thyroid specimens were studied for the expression of 768 miRNAs using PCR-Microarrays. MiRNA expression was different between PD and oPD thyroid carcinomas, demonstrating individual clusters on the clustering analysis. Both tumour types showed upregulation of miR-125a-5p, -15a-3p, -182, -183-3p, -222, -222-5p, and downregulation of miR-130b, -139-5p, -150, -193a-5p, -219-5p, -23b, -451, -455-3p and of miR-886-3p as compared with normal thyroid tissue. In addition, the oPD thyroid carcinomas demonstrated upregulation of miR-221 and miR-885-5p. The difference in expression was also observed between miRNA expression in PD and well-differentiated tumours. The CHAID algorithm allowed the separation of PD from well-differentiated thyroid carcinomas with 73-79% accuracy using miR-23b and miR-150 as a separator. Kaplan-Meier and multivariate analysis showed a significant association with tumour relapses (for miR-23b) and with tumour-specific death (for miR-150) in PD and oPD thyroid carcinomas. MiRNA expression is different in conventional and oPD thyroid carcinomas in comparison with well-differentiated thyroid cancers and can be used for discrimination between these tumour types. The newly identified deregulated miRNAs (miR-150, miR-23b) bear the potential to be used in a clinical setting, delivering prognostic and diagnostic informations.
Department of Pathology and Laboratory Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA Institute of Pathology, University of Bern, Murtenstrasse 31, 3010 Bern, Switzerland Institute of Surgical Pathology, University Hospital Zurich, 8091 Zurich, Switzerland Institute of Surgical Pathology, Triemlispital Zurich, 8063 Zurich, Switzerland.
Matthias S
MS
Dettmer
Aurel
A
Perren
Holger
H
Moch
Paul
P
Komminoth
Yuri E
YE
Nikiforov
Marina N
MN
Nikiforova
D002454:Cell Differentiation / Q000235:genetics*; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D011379:Prognosis; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology
D035683:MicroRNAs
diagnosis; follicular thyroid carcinoma; miRNA profiling; papillary carcinoma; poorly differentiated carcinoma; prognosis; thyroid cancer