Real-time Quantitative Analysis of E-cadherin Expression in ret/PTC-1-Activated Thyroid Neoplasms

Abstract

Papillary thyroid carcinoma (PTC), the most common variety of thyroid cancer, is found in a variety of morphologic variants, usually grows slowly, and is clinically indolent, although rare, aggressive forms, with local invasion or distant metastases, occur. Our group has previously demonstrated an association between Hashimoto thyroiditis and ret/PTC-1 activation, and have hypothesised that c-ret activation might be implicated in immune reaction to thyroid epithelium. The objective of this study was to examine expression of the cellular adhesion molecule, E-cadherin, in various thyroid tumor types and Hashimoto thyroiditis in the context of ret/PTC-1 positivity by using laser capture microdissection and TaqMan reverse transcription-polymerase chain reaction (RT-PCR). Variable down-regulation of E-cadherin among carcinomas was demonstrated, with anaplastic carcinomas showing little or no expression. Follicular thyroid carcinomas consistently had significantly decreased E-cadherin expression compared with papillary thyroid carcinomas. The ret/PTC-1-positive papillary thyroid carcinoma (PTCret+) and Hashimoto thyroiditis cases had consistently lower E-cadherin expression levels than the corresponding ret/PTC-1-negative papillary carcinomas (PTCret-), suggesting not only an association between ret activation and the loss of cellular adhesion but also, more significantly, an association between papillary thyroid carcinoma and Hashimoto thyroiditis.

Diagnostic utility of immunohistochemical panel in various thyroid pathologies

“…Contrary to our data and above-mentioned studies, Smyth et al demonstrated a significant reduction of E-CAD expression in FC when compared to normal thyroid or FA but not a significant diminution of E-CAD expression in PTC [38].…”

Ret/PTC Chimeric Transcripts in an Irish Cohort of Sporadic Papillary Thyroid Carcinoma

“…Monaco et al (25) speculate that protein interactions, mediated by protein products of the genes fused to ret at the 5Ј terminal (H4 and ELE-1), affect the signaling of the specific ret/PTC isoforms. We have previously demonstrated consistently reduced expression of E-cadherin in ret/PTC-1-positive cohorts in comparison with normal thyroid tissue (26). A comparable study assessing expression levels of E-cadherin in ret/PTC-3-positive and -negative normal controls failed to demonstrate a significant reduction (Smyth, P., S. P. Finn, and O. Sheils, unpublished data).…”

Snail Family Transcription Factors Are Implicated in Thyroid Carcinogenesis

“…CDH1 expression is decreased in classic papillary thyroid carcinoma 3,6 -10 and its diffuse sclerosing variant 9 and also in follicular carcinoma. 3,7,8,[11][12][13] Rarely, this decrease in expression is attributable to mutation of the CDH1 gene, 7,9 loss of heterozygosity, 7 or hypermethylation of the CDH1 promoter. 9 In most tumors the mechanism of CDH1 down-regulation is, however, unknown.…”