Gene expression in papillary thyroid carcinoma reveals highly consistent profiles

Abstract

Papillary thyroid carcinoma (PTC) is clinically heterogeneous. Apart from an association with ionizing radiation, the etiology and molecular biology of PTC is poorly understood. We used oligobased DNA arrays to study the expression profiles of eight matched pairs of normal thyroid and PTC tissues. Additional PTC tumors and other tissues were studied by reverse transcriptase-PCR and immunohistochemistry. The PTCs showed concordant expression of many genes and distinct clustered profiles. Genes with increased expression in PTC included many encoding adhesion and extracellular matrix proteins. Expression was increased in 8͞8 tumors for 24 genes and in 7͞8 tumors for 22 genes. Among these genes were several previously known to be overexpressed in PTC, such as MET, LGALS3, KRT19, DPP4, MDK, TIMP1, and FN1. The numerous additional genes include CITED1, CHI3L1, ODZ1, N33, SFTPB, and SCEL. Reverse transcriptase-PCR showed high expression of CITED1, CHI3L1, ODZ1, and SCEL in 6͞6 additional PTCs. Immunohistochemical analysis detected CITED1 and SFTPB in 49͞52 and 39͞52 PTCs, respectively, but not in follicular thyroid carcinoma and normal thyroid tissue. Genes underexpressed in PTC included tumor suppressors, thyroid function-related proteins, and fatty acid binding proteins. Expression was decreased in 7͞8 tumors for eight genes and decreased in 6͞8 tumors for 19 genes. We conclude that, despite its clinical heterogeneity, PTC is characterized by consistent and specific molecular changes. These findings reveal clues to the molecular pathways involved in PTC and may provide biomarkers for clinical use.

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.…”

Detection and molecular characterisation of thyroid cancer precursor lesions in a specific subset of Hashimoto's thyroiditis

“…Molecular and immunohistochemical studies directed to detect specific gene profiles and related proteins in thyroid cancer have been extensively reported in literature (Bartolazzi et al, 2001;Huang et al, 2001;Ruco et al, 2001;Wreesmann et al, 2002). Experimental data, mostly arising from the molecular analysis of papillary thyroid carcinoma (PTC), contributed to identify a panel of genes overexpressed in thyroid malignancy.…”

“…Experimental data, mostly arising from the molecular analysis of papillary thyroid carcinoma (PTC), contributed to identify a panel of genes overexpressed in thyroid malignancy. Among these genes, FN-1 (fibronectin-1), and MET (hepatocyte growth factor receptor) gene have been found consistently overexpressed in PTC (Huang et al, 2001).…”

“…Research in this field has recently been focused on LGALS3 gene that codes for the bgalactosil binding protein called galectin-3. This lectin molecule, which is expressed in the vast majority of PTC, as well as in follicular carcinoma, is directly involved in transformation of follicular thyroid cells and in regulation of apoptosis (Bartolazzi et al, 2001;Huang et al, 2001;Takenaka et al, 2003;Yang and Liu, 2003).…”