Expression of Tenascin C, EGFR, E-Cadherin, and TTF-1 in Medullary Thyroid Carcinoma and the Correlation with RET Mutation Status

Abstract

Tenascin C expression correlates with tumor grade and indicates worse prognosis in several tumors. Epidermal growth factor receptor (EGFR) plays an important role in driving proliferation in many tumors. Loss of E-cadherin function is associated with tumor invasion and metastasis. Thyroid transcription factor-1 (TTF-1) is involved in rearranged during transfection (RET) transcription in Hirschsprung’s disease. Tenascin C, EGFR, E-cadherin, TTF-1-expression, and their correlations with RET mutation status were investigated in 30 patients with medullary thyroid carcinoma (MTC) (n = 26) or C-cell hyperplasia (n = 4). Tenascin C was found in all, EGFR in 4/26, E-cadherin in 23/26, and TTF-1 in 25/26 MTC. Tenascin C correlated significantly with tumor proliferation (overall, r = 0.61, p < 0.005; RET-mutated, r = 0.81, p < 0.01). E-cadherin showed weak correlation, whereas EGFR and TTF-1 showed no significant correlation with tumor proliferation. EGFR, E-cadherin, and TTF-1 showed weak correlation with proliferation of RET-mutated tumors. Correlation between TTF-1 and tenascin C, E-cadherin, and EGFR was r = −0.10, 0.37, and 0.21, respectively. In conclusion, MTC express tenascin C, E-cadherin, and TTF-1. Tenascin C correlates significantly with tumor proliferation, especially in RET-mutated tumors. EGFR is low, and tumors expressing EGFR do not exhibit higher proliferation. TTF-1 does not correlate with RET mutation status and has a weak correlation with tenascin C, E-cadherin, and EGFR expression.

RET-mediated modulation of tumor microenvironment and immune response in multiple endocrine neoplasia type 2 (MEN2)

“…Interestingly, these markers have also been described in areas of autoimmune thyroiditis associated to some cases of MTCs, suggesting a function in inflammatory tissue remodeling. Finally, Tn-C expression was seen in the stroma of both hereditary and sporadic cases of MTCs (Koperek et al 2009, Steiner et al 2016. Although the mesenchymal tissue of the thyroid is prone to develop fibrosis in both inflammatory (i.e., Riedel's, Hashimoto, De Quervain's, fibrotic nodules) as well as in neoplastic conditions (Mai & Hogan 2016), not many studies have been conducted to identify the characteristics of MTC desmoplastic stroma.…”

Two distinct E3 ligases, SCFFBXL19and HECW1, degrade thyroid transcription factor 1 in normal thyroid epithelial and follicular thyroid carcinoma cells, respectively

“…Among thyroid tumors, TTF1 is expressed in all tumors of follicular derivation, such as follicular adenoma and follicular and papillary carcinoma (10)(11)(12). The C-cell-derived medullary carcinomas are positive for TTF1 immunoreactivity (13,14). Moreover, TTF1 is a useful predictor of resistance for radioactive iodine therapy (15,16).…”

Current Knowledge in Thyroid Cancer—From Bench to Bedside

“…Several manuscripts focusing on the diagnosis [ 11 , 12 , 13 , 14 , 15 ], characterisation [ 16 , 17 , 18 , 19 ], and treatment [ 20 , 21 , 22 ] of thyroid cancer, as well as on alterations of thyroid cancer cells by altered gravity [ 23 , 24 ] or radiation damage of the thyroid gland [ 25 ], including genetics, proteomics, molecular, and cell biology, are published in this Special Issue. In addition, an original publication reports that the polymorphism loci of the tumour necrosis factor superfamily member 4 ( TNFSF4 ) gene is related to early-onset autoimmune thyroid diseases [ 26 ].…”

“…The next group of publications mainly focused on cancer characterisation [ 16 , 17 , 18 , 19 ]. The study of Ruggeri et al [ 16 ] described the human epidermal growth factor receptor 2 (HER2) status in sporadic thyroid carcinomas of follicular cell origin.…”

“…Steiner et al [ 19 ] focused on the expression of tenascin C, E-cadherin, EGFR, and thyroid transcription factor 1 (TTF-1) in medullary thyroid carcinomas (MTC). Tenascin C found in all MTC correlated with proliferation, mainly in RET-mutated tumours.…”