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.

Highlights

  • Medullary thyroid carcinoma (MTC) may arise sporadically in about 75% of cases or as part of multiple endocrine neoplasia type 2 (MEN2) syndrome in 20%–25% of cases [1]

  • We we investigated investigated the expression of tenascin C, epidermal growth factor receptor (EGFR), E-cadherin, and transcription factor-1 (TTF-1) in MTC, and their correlation with rearranged during transfection (RET) mutation status

  • We investigated if RET mutation correlates with a higher expression of tenascin C, EGFR, E-cadherin, or TTF-1

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Summary

Introduction

Medullary thyroid carcinoma (MTC) may arise sporadically in about 75% of cases or as part of multiple endocrine neoplasia type 2 (MEN2) syndrome in 20%–25% of cases [1]. MEN 2 syndromes are caused by activating mutations of the proto-oncogene rearranged during transfection (RET) [2]. A loss of function mutation of RET leads to Hirschsprung’s disease [3]. Tenascin C is an extracellular glycoprotein complex expressed by a variety of cells including epithelial, stromal, and tumor cells [4]. It is overexpressed in a wide variety of tumors including gliomas, where it was originally discovered [5]. Koperek et al [7] found tenascin C expression in medullary microcarcinoma and C-cell hyperplasia and suggested that stromal tenascin C

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