MicroRNA analysis as a potential diagnostic tool for papillary thyroid carcinoma

Abstract

MicroRNA (miRNA) microarray analysis has consistently found altered expression of miRNAs in thyroid tumors, suggesting their roles in thyroid carcinogenesis. To explore whether this differential expression can be used as a diagnostic tool in surgical pathology and fine-needle aspirate (FNA) specimens, the expression of selected miRNA was evaluated by quantitative RT-PCR, using total RNA from 84 formalin-fixed paraffin-embedded tissues and 40 ex vivo aspirate specimens. miRNA from all paraffin-embedded tissues and all but one FNA sample were found to be analyzable, with paraffin sections yielding better miRNA quality. Preliminary analysis of 6 miRNAs in 10 papillary thyroid carcinoma and 10 follicular adenoma identified significant overexpression of miR-146b, -221, and -222 in papillary thyroid carcinoma (Po0.02), but not miR-146a, -155, or -187 (P40.08). The expression of these first three miRNAs was examined in a series of 5 normal thyroid, 11 hyperplastic nodules, 24 follicular adenoma, 27 classical papillary thyroid carcinoma, 5 follicular variant papillary thyroid carcinoma, 2 follicular carcinoma, and 10 encapsulated follicular lesions with partial nuclear features of papillary carcinoma. Results showed miR-146b to be most consistently overexpressed in both classical papillary carcinoma and follicular variants, whereas all other groups showed lower expression at a similar level (Po0.001 for pair-wise comparisons between papillary carcinoma and all other groups). Follicular lesions with partial features of papillary carcinoma all showed low miR-146b levels similar to other non-papillary carcinoma groups, suggesting that they are biologically distinctive from papillary carcinoma. miR-221 and miR-222 also showed higher expression in papillary carcinoma, but with substantial overlaps with the other groups. When applied to 40 FNA samples of various lesions, only miR-146b and miR-222 persisted as distinguishing markers for papillary carcinoma. We concluded that miRNAs, particularly miR-146b, might potentially be adjunct markers for diagnosing papillary thyroid carcinoma in both FNA and surgical pathology specimens.

Differential miRNA expression profiles in variants of papillary thyroid carcinoma and encapsulated follicular thyroid tumours

“…As for diagnostic purposes, only miRNA 146b reliably distinguish the conventional and tall cell variant from benign thyroid lesions in individual cases, whereas all other miRNAs show substantial overlap. This is in accordance with a study by Chen et al (2008) who found miRNA 146b to be most consistently overexpressed in both conventional and follicular variants when compared with 'borderline' follicular lesions, although the number of five follicular variants in their study is rather small.…”

“…In accordance with previous studies (He et al, 2005;Pallante et al, 2006;Tetzlaff et al, 2007;Chen et al, 2008;Nikiforova et al, 2008) the analysis of a limited set of miRNAs represents a reliable method to distinguish PTC from benign thyroid lesions (for review see Table 1). Considering the mean DCt values of all miRNAs analysed in our study, we showed highly significant changes between PTC and MNG/FA.…”

“…A large number of miRNAs are involved in almost every major cellular function (Cowland et al, 2007) and as a consequence, deregulation of miRNAs has also been linked to a broad variety of cancers (Calin et al, 2002Michael et al, 2003;Takamizawa et al, 2004;Iorio et al, 2005;Lu et al, 2005;Mattie et al, 2006;Murakami et al, 2006;Volinia et al, 2006). Recently, a few studies reported on deregulated miRNAs in PTC using miRNA microarrays (He et al, 2005;Pallante et al, 2006;Tetzlaff et al, 2007;Nikiforova et al, 2008) and RT -PCR TaqMan miRNA assay (Tetzlaff et al, 2007;Chen et al, 2008;Nikiforova et al, 2008), identifying a limited number of miRNAs that are significantly upregulated in PTC compared with normal thyroid tissue (He et al, 2005;Pallante et al, 2006;Chen et al, 2008;Nikiforova et al, 2008), hyperplastic nodules (Chen et al, 2008;Nikiforova et al, 2008) and multinodular goitre (Tetzlaff et al, 2007; for review, see Table 1), suggesting miRNA analysis as a promising tool in diagnostic thyroid pathology.…”

Specific Alterations of MicroRNA Transcriptome and Global Network Structure in Colorectal Carcinoma after Cetuximab Treatment

“…Moreover, among the targets of miR-486-5p, there is PIK3R1 that is known to be upregulated in responsive patients after cetuximab treatment (39). miR146b-3p has been reported to be an unfavorable cancer prognostic marker for patients with squamous cell lung cancer or papillary thyroid carcinoma (40)(41)(42). Interestingly, its upregulation is statistically associated with BRAF mutation in papillary thyroid carcinoma.…”

Chromosome banding analysis of cells from fine-needle aspiration biopsy samples from soft tissue and bone tumors: is it clinically meaningful?

“…Both FISH and RT-PCR have been shown to be very useful when searching for specific neoplasiaassociated rearrangements, such as fusion genes, in samples with small numbers of tumor cells [11,12]. are some promising results on FNA material from papillary thyroid carcinoma and non-small cell lung carcinomas [13][14][15]. The same techniques should be applicable also to soft tissue and bone tumors, but further studies are needed to evaluate this.…”