MicroRNA signature of thyroid tumors and its possible diagnostic application for the differential diagnosis of follicular thyroid cancer and follicular adenomas

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The differentiation of the rarely occurring thyroid carcinoma from the frequently occurring benign thyroid nodules is a frequent and challenging issue. Fine-needle aspiration cytology (FNAC) is a very sensitive and specific tool for the differential diagnosis of thyroid nodules. However, it reveals the inconclusive result of follicular proliferation (characteristic for both follicular thyroid carcinoma and follicular adenoma) in up to 20%. Furthermore, the molecular etiology of cold thyroid nodules (CTNs) which comprise approximately 85% of thyroid nodules and which are characterized by increased proliferation, is still limited. However, recent microarray studies showed a specific CTN mRNA proliferation signature that overlaps only partly with the proliferation signature found in papillary thyroid carcinoma. Moreover, investigations of different tumor types revealed a prominent modulation of proliferation by microRNAs (miRNAs). Furthermore, it has recently been shown that miRNA profiles are superior to mRNA profiles in the differential diagnosis of tumor types that cannot be determined on the basis of tumor histologies. Therefore, the first goal of this proposal is to identify and to verify the miRNA correlates of the mRNA proliferation signatures of follicular thyroid carcinomas and cold thyroid nodules (mostly follicular adenomas), which are likely to explain the increased proliferation (common miRNA set in FTCs and CTNs) and which most likely drive malignant transformation (private miRNA set of FTCs). The second goal will be to investigate the private miRNA signatures of CTNs and FTCs for their diagnostic application for the inconclusive FNAC result follicular proliferation.