Microarray Analysis of Thyroid Nodule Fine-Needle Aspirates Accurately Classifies Benign and Malignant Lesions

Abstract

Current preoperative diagnostic procedures for thyroid nodules rely mainly on the cytological interpretation of fine-needle aspirates (FNAs). DNA microarray analysis has been shown to reliably distinguish benign and malignant thyroid nodules in surgically resected specimens, but its diagnostic potential in thyroid FNA has not been examined. In the present study, the expression profiles of 50 benign thyroid lesions and papillary thyroid carcinoma tissue samples were compared, generating a list of 25 differentially expressed genes from this training set. A test set of 22 FNA specimens was evaluated by unsupervised hierarchical cluster analysis using this gene list, and the results were compared to FNA cytology. FNA specimens were found to fall into three clusters: malignant (n ‫؍‬ 10), benign (n ‫؍‬ 7), and indeterminate (n ‫؍‬ 5). The benign and malignant groups showed complete concordance with the final histological diagnosis except for one histologically benign lesion, which was rediagnosed as follicular variant of papillary thyroid carcinoma on histological review. Paired analysis between FNA and matched tissues samples illustrated adequate sampling with FNA. These results illustrate that microarray analysis of FNA is feasible and has the potential to improve the accuracy of FNA in categorizing benign from malignant lesions beyond routine cytological evaluation.

MicroRNA analysis as a potential diagnostic tool for papillary thyroid carcinoma

“…We and others have previously shown that papillary thyroid carcinoma could be separated from benign nodules, ie follicular adenomas and hyperplastic nodules, by their mRNA expression profiles using cDNA microarray analysis. [42][43][44] By qRT-PCR evaluation, our preliminary data also showed that by using fresh-frozen materials, most cases of papillary carcinoma and follicular adenoma can also be separated by their expression of a small panel of several genes, namely CK19, CITED1, galectin 3, deiodinase 1, thyroglobulin, and pendrin. 45 However, these mRNA-based assays were found to be less reliable when applied to formalin-fixed, paraffin-embedded tissues, primarily due to the suboptimal RNA qualities in these specimens (unpublished data).…”

Utility of malignancy markers in fine-needle aspiration cytology of thyroid nodules: comparison of Hector Battifora mesothelial antigen-1, thyroid peroxidase and dipeptidyl aminopeptidase IV

“…Molecular methods such as mutation detection or expression profile analysis are promising but cannot currently be used for routine practice (Eszlinger et al, 2006;Griffith et al, 2006;Lubitz et al, 2006;Tetzlaff et al, 2006;Finn et al, 2007). On the contrary, immunocytochemistry (ICC) and cytoenzymology (CE) are widely available and can be performed on smears (De Micco et al, 1994a), cell blocks (Sack et al, 1997), or liquid-based preparation (Rossi et al, 2005).…”

Three-Gene Molecular Diagnostic Model for Thyroid Cancer

“…However, since the cytological features of thyroid lesions are often not sufficiently distinct enough to distinguish between benign and malignant lesions, preoperative differentiation is often difficult and frequently inaccurate. To improve the sensitivity and specificity of cytological diagnosis, several studies have been conducted in the last decade to identify diagnostic molecular markers that can be used as an adjunct to FNA-based cytology (8,(10)(11)(12)(13)(14)(15)(16)(17)(18)(22)(23)(24)(25).…”

“…Over the past decade, studies by others and our group have revealed differences in gene expression between benign and malignant thyroid tumors (10)(11)(12)(13)(14)(15)(16)(17)(18). However, no study has included all of the thyroid tumor types that have associated suspicious FNA cytology (5), nor successfully implemented them as a diagnostic adjunct to FNA in a large cohort of patients with suspicious thyroid lesions.…”