microRNA Expression Array Identifies Novel Diagnostic Markers for Conventional and Oncocytic Follicular Thyroid Carcinomas
Matthias Dettmer, Mary Beth Durso, Paul Komminoth, Holger Moch, Aurel Perren, Yuri E Nikiforov, Marina N Nikiforova. University of Pittsburgh, Pittsburgh; Triemlispital, Zurich, Switzerland; University Hospital, Zurich, Switzerland; University of Bern, Bern, Switzerland
Background: Follicular carcinoma (FTC) and oncocytic follicular carcinoma (oFTC) represent thyroid tumors that frequently pose diagnostic challenge, both on cytologic and histopathologic analysis. Several miRNAs have been previously reported as reliable markers in conventional papillary thyroid carcinomas, however, limited information is available for FTC and oFTC. The aim of this study was to identify candidate miRNA markers that can be used diagnostically.
Design: Forty two follicular thyroid carcinomas (21 FTC, 21 oFTC) and 11 normal thyroid tissues were studied for expression of 380 miRNAs using Human Microarray Assays (Applied Biosystems) on ABI7900. miRNAs were isolated using Trizol reagents from frozen thyroid tissue (n=18) and using RecoverAll Total Nucleic Acid kit (Ambion) from FFPE tissue specimens (n=24). Data analysis was performed with Data Assist v3.0 (Applied Biosystems) program. Expression of candidate miRNA markers was individually validated in all samples by RT-PCR.
Results: Both types of folicular carcinomas (FTC and oFTC) demonstrated deregulatation in miRNA expression as compared to normal thyroid tissue with significant number of downregulated miRNAs and several upregulated miRNAs. Overall, the levels of miRNA expression were different between these tumor groups and the unsupevised hierarchical clustering analysis revealed individual cluster for oFTC and FTC. miRNAs upregulated in both tumor types were miR-182 (3-8 folds), miR-183 (4-7 folds), miR-221 (3-30 folds), and miR-222 (2-10 folds) and miRNAs strongly (>4 folds) downregulated were 199a-3p and miR-455-5p. Moreover, extremely high upregulation of miR-885-5p (34-56 folds, p<0.01) was detected only in oFTC.
Conclusions: This study shows different miRNA expression profiles in FTC and oFTC, supporting a notion that they represent independent tumor subtypes. Several miRNAs were found sugnificantly upregulated and downregulated in follicular carcinomas as compared to normal thyroid. miR-885-5p is a novel miRNA found to be highly upregulated in oFTCs and can be used as a diagnostic marker of oFTC in surgical and FNA samples.
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 17, Tuesday Afternoon