Molecular Profiling Distinguishes Papillary Carcinoma from Benign Thyroid Nodules

Abstract

Recently we identified a molecular basis for differentiating benign and malignant follicular thyroid tumors. The purpose of these studies was to determine whether molecular analysis can be used to differentiate papillary thyroid carcinomas from benign thyroid nodules. Gene expression patterns of 14 papillary thyroid carcinomas and 21 benign tumors were analyzed by oligonucleotide array analysis. The carcinomas included seven classical papillary thyroid carcinomas (PTC) and seven follicular variant of PTC (FVPTC), and the benign tumors included 14 follicular adenomas and seven hyperplastic nodules. A hierarchical clustering analysis was performed to examine the groups for potential differences. The combined PTC and FVPTC groups had a distinct gene expression profile compared with the benign lesions. The sensitivity for a diagnosis of carcinoma was 93%, with a 100% specificity (one FVPTC clustered with the benign nodules). Cancer gene profiles contained both known (Met and galectin-3) and previously unidentified genes. Gene profiling is a reliable means of distinguishing PTC, FVPTC, and benign tumors of the thyroid. These gene profiles may provide insight into the pathogenesis of papillary thyroid carcinoma and may ultimately enhance the preoperative diagnosis of thyroid nodules on a molecular basis.

Class distinction between follicular adenomas and follicular carcinomas of the thyroid gland on the basis of their signature expression

“…Such a failure could be explained by the great similarity in overall gene expression profiles observed between the 2 sample groups, as demonstrated by Figures 1 and 2, which may be further indication that the 2 lesions are similar not only phenotypically but also at the level of gene expression. Our data are in disagreement with those published previously by Finley et al and by Barden et al, [11][12][13] who identified a set of genes that, by clustering algorithms, could distinguish between adenomas and follicular carcinomas. This discrepancy may be explained by the number and identity of the genes present in our arrays compared with the arrays used by other groups or by differences in mathematical and statistical approaches.…”

“…Using oligonucleotide arrays, Finley et al identified differentially expressed genes among carcinomas, adenomas, and hyperplastic nodules; and the expression of those genes was used to cluster samples that represented different pathologies. 11,12 A similar technique was employed in the comparison of follicular carcinomas and adenomas and demonstrated different profiles after hierarchical clustering. 13 Recently, we described the identification of molecular classifiers that could distinguish between malignant and nonmalignant lesions of the gastric mucosa.…”

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).…”

A molecular expression signature distinguishing follicular lesions in thyroid carcinoma using preamplification RT-PCR in archival samples

“…To date, a number of microarray studies have shown metallothioneins to be downregulated in thyroid carcinoma. 7,14,15 Huang et al 14 expanded on their initial microarray experiment by trying to identify novel tumour suppressor genes involved in thyroid carcinogenesis. They found that MT1G was downregulated in papillary thyroid carcinoma consequent to hypermethylation.…”