MicroRNA Expression Profiles in Poorly Differentiated Thyroid Carcinomas
Matthias S Dettmer, Aurel Perren, Paul Komminoth, Holger Moch, Yuri E Nikiforov, Marina N Nikiforova. University of Pittsburgh Medical Center, Pittsburgh, PA; University of Bern, Bern, Switzerland; Triemlispital, Zurich, Switzerland; University Hospital Zurich, Zurich, Switzerland
Background: Conventional and oncocytic poorly differentiated thyroid carcinomas (PD and oPD) are among the most difficult thyroid tumors to be diagnosed. In contrast to papillary thyroid carcinomas (PTC), where some miRNAs are established as reliable markers, this information is very limited for PD and oPD. The aim of this study was to characterize the miRNA profile for PD and oPD and identify miRNAs which could eventually serve as diagnostic and prognostic markers in thyroid specimens.
Design: Ninty-eight thyroid carcinomas (14 PD, 12 oPD, 44 PTC and 28 follicular thyroid tumors (FTC)) and 8 normal thyroid tissues were studied for expression of 768 miRNAs using Human Microarray Assays (Applied Biosystems) on ABI 7900. miRNAs were isolated using using RecoverAll Total Nucleic Acid kit (Ambion) from FFPE tissue specimens (n=106). The data analysis was performed with Data Assist v3.1 (Applied Biosystems) and SPSSv.17 (IBM) program.
Results: miRNA expression was different between PD and oPDs demonstrating individual clusters on the unsupervised hierarchical clustering analysis. Both, PD and oPDs showed upregulation of miR-125a-5p, miR-15a-3p, miR-182, miR-183-3p, miR-222, miR-222-5p. Downregulation of miR-130b, -139-5p, -150, -193a-5p, -219-5p, -23b, -451, -455-3p and of miR-886-3p was observed. In addition, upregulation of miR-221 and miR-885-5p was strongly detected in oPD. Only significant deregulated miRNAs in PD and oPD carcinomas are reported. The expression of these markers was compared to their expression in PTC and FTC. Kaplan-Meier analysis demonstrated a significant association with tumorrelapse for miR-139-5p, -183-3p, -221, -222, -222-5p, -23b and miR-886-3p. MiR-15a-3p, -23b and miR-885-5p were significant correlated with tumor specific death.
Conclusions: PD and oPD are an ongoing diagnostic challenge. The new identified specific deregulated miRNAs bear the potential to facilitate their diagnoses in a daily preoperative and postoperative routine setting. Furthermore, the prognostic information of these markers may help clinicians in the future to treat patients with these rare neoplasms better. Further studies are required to validate these findings.
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 34, Wednesday Afternoon