Analysis of Deregulated miRNAs is Helpful to Distinguish Poorly Differentiated Thyroid Carcinoma from Papillary Thyroid Carcinoma

Abstract

Poorly differentiated thyroid carcinoma (PDTC) is defined as a malignant follicular cell derived neoplasm, both morphologically and biologically intermediate between well differentiated and anaplastic thyroid carcinoma (ATC). In the present study we investigated the expression levels of two distinct sets of miRNAs ('set 1': miRNA-146b, -181b, -21, -221, -222, all shown to be significantly upregulated in papillary thyroid carcinoma [PTC]; 'set 2': miRNA-30d, -125b, -26a, -30a-5p, and let7c, all downregulated in ATC) in a series of 15 PDTC (including 3 mixed PDTC/PTC), 9 'pure' PTC, and 9 ATC. Compared to normal thyroid tissue all 'set 1' miRNAs were significantly upregulated in PTC (p<0.001); in ATC 4/5 miRNAs were upregulated (p<0.001) whereas in PDTC the expression levels of all 5 miRNAs did not differ significantly from normal thyroid. All miRNAs of 'set 2' were significantly upregulated in PTC (p<0.004) and downregulated in ATC (p<0.03); in PDTC only 3/5 were downregulated (p<0.011). All 10 miRNAs investigated differed significantly (p<0.003) between PTC and PDTC. In the histologically differentiated PTC compound of mixed PDTC/PTC cases, however, miRNA expression levels of all 10 miRNAs investigated lacked significant difference from those found in the PDTC compound, whereas 6/10 miRNAs differed significantly from 'pure' PTC. Our results indicate that analysis of distinct sets of miRNAs represent useful tools to distinguish PDTC from 'pure' PTC. Additionally our findings suggest that lack of deregulation of some miRNAs may select a subset of PTC prone to progression to PDTC.

MicroRNA Signature in Thyroid Fine Needle Aspiration Cytology Applied to “Atypia of Undetermined Significance” Cases

“…Our work and that of others indicate that an aberrant miR expression profile can separate PTC from normal thyroid tissue and benign thyroid lesions. In thyroid cancer other than PTC, miR expression profiles have also been reported (18,(20)(21)(22); miR-197, -346, -146b, -221, -222, and -187 are reported to be overexpressed in FTC (20,21), while miR30d and -138 were downregulated in ATC and poorly differentiated carcinoma (18,22). miR-302c showed the most dramatic upregulation in ATC (20).…”

“…Several lines of evidence indicate that aberrant miR expression profiles are able to separate thyroid cancers from benign thyroid lesions and normal thyroid tissue, suggesting that miRs may have potential use as a diagnostic tool in thyroid pathology (16)(17)(18)(19)(20)(21)(22)(23)(24)(25). We had previously used microarray expression profiling to characterize deregulation of miR expression in fresh snap-frozen PTC samples and identified a panel of miRs upregulated in PTCs, including miR-146b, -221, and -222 (16).…”

An update on molecular biology of thyroid cancers

“…There are several reports displaying changes in miRNA profiles in thyroid cancers as compared to normal thyroid tissues [143,144]. Based on cellular origin and degree of tumor differentiation, different miRNAs are expressed in thyroid cancer [145]. Particularly miR-222, miR-221, and miR-146b have been found to be the most upregulated miRNAs in PTC.…”

“…There are several studies reporting overexpression of miRNAs including miR-222, miR-221, and miR-146b in PTC and these miRNAs may be of diagnostic potential [143][144][145][146][147][148][149][150][151]. In a recent study, a panel of seven miRNAs was used in thyroid FNAB samples [223].…”

Different micro-RNA expression profiles distinguish subtypes of neuroendocrine tumors of the lung: results of a profiling study

“…2,[12][13][14][15][16][17] Aberrant miRNA expression has been reported to be involved in the pathogenesis of Alzheimer's disease, 18 cardiovascular disease, 19 spinal motor neuron anomalies, 20 and numerous others. 2 Furthermore, deregulated expression of miRNAs has been identified in a variety of human malignancies, 12,13,[21][22][23][24][25][26][27][28][29] suggesting that miRNAs function as potential oncogenic factors or tumor suppressors, depending on the cell type or tissue investigated and their target genes. 3 For example, the miR-34 family members are direct transcriptional targets of p53 and their expression induces cell cycle arrest in cancer cell lines.…”