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Increased expression of endothelin‐1 and its mitogenic receptor ET A in human papillary thyroid carcinoma
Author(s) -
Donckier Julian E.,
Michel Luc,
Van Beneden Ronald,
Delos Monique,
Havaux Xavier
Publication year - 2003
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1046/j.1365-2265.2003.01855.x
Subject(s) - medicine , endocrinology , thyroiditis , thyroid , thyroid carcinoma , immunohistochemistry , pathophysiology , endothelin 1 , receptor
Summary objective Since the isolation of endothelin‐1 (ET‐1) in 1988, there has been tremendous interest in the pathophysiological roles of ET‐1 as a vasoconstrictive and mitogenic peptide. Whereas ET‐1 is mainly released by vascular endothelial cells, it also proved to be produced by various tissues including the thyroid. Because of its mitogenic properties in malignancy and its role as an inflammatory modulator, ET‐1 could be involved in thyroid carcinogenesis and thyroiditis. design and patients Studies were performed in human thyroid samples obtained at the time of surgery from 39 men and women aged 15–72 years. Thyroid samples were classified in four groups according to conventional histology: normal thyroid ( n = 7) papillary thyroid carcinoma ( n = 12), Hashimoto's thyroiditis ( n = 9) and benign nontoxic nodular goitres ( n = 11). Immunohistochemistry and real‐time quantitative polymerase chain reaction were used to determine the expression of ET‐1 and its receptors (ET A R and ET B R). results ET‐1 and ET A R mRNA levels were, respectively, 3·8 ± 1·3 and 4·1 ± 1·5 times greater ( P < 0·001) in papillary thyroid carcinoma than in normal thyroid. Expression of ET B R was unaltered. In Hashimoto's thyroiditis, ET‐1 and ET A R were also overexpressed ( P < 0·005). Furthermore, immunohistochemistry demonstrated a greater percentage of ET‐1‐positive follicular cells in these conditions ( P < 0·001). In nodular goitres, the expression was increased by 1·7 ± 0·7 times ( P < 0·05) but expression of receptors remained unchanged. conclusions ET‐1 and ET A R overexpression observed in thyroid carcinoma suggest a mitogenic role of ET‐1 that theoretically could be countered by ET A R antagonists. ET‐1 and ET A R overexpression in thyroiditis supports a role of ET‐1 in the inflammatory process.