Presence of endothelin-1 in the normal and pathological human thyroid

Abstract

An immunohistochemical study with two rabbit polyclonal antibodies I-AR76 and CA-08-351 against Endothelin-1 (ET-1) was performed in 133 human thyroid specimens: 5 normal thyroids, 30 multinodular goiters (15 toxic and 15 nontoxic), 20 Graves' diseases, 5 Hashimoto's thyroiditis, 26 adenomas (6 Hürthle cell, 16 toxic and 4 nontoxic), 30 classic papillary carcinomas, 3 minimally invasive follicular carcinomas, 1 widely invasive follicular carcinoma, 3 undifferentiated carcinomas and 10 medullary carcinoma. All normal thyroids, non toxic multinodular goiters and non toxic adenomas, 4 (66%) Hürthle cell adenomas, 3 (15%) Graves' diseases, 1 (33%) case of minimally invasive follicular carcinoma showed rare follicular cells with weak cytoplasmic immunoreactivity. Many immunoreactive follicular cells, with or without oxyphilic changes, were observed in all specimens of Hashimoto's disease, while the lymphocytic infiltrate was always negative. Twenty-seven (90%) classic papillary carcinomas were positive. Immunoreactivity was intracytoplasmic, weak in 14 cases and intense in 13. The cells of toxic adenoma and toxic multinodular goiter were negative, whereas the acellular stroma was intensely positive in both cases. Medullary and undifferentiated carcinomas were negative. These results show ET-1 immunoreactivity in normal and pathological human thyroids. In particular, the high content of this peptide in the thyroid papillary carcinoma suggests that ET-1, whose mitogenic role has recently been emphasized, could be involved in the growth of this tumor.

Expression profile of endothelin 1 and its receptor endothelin receptor A in papillary thyroid carcinoma and their correlations with clinicopathologic characteristics

“…In our investigation, ET-1 immunostaining showed high expression in 94% of cases and ET A R staining showed high expression in 95% of cases. The results confirmed the findings of high expression of proteins in two previous studies on papillary thyroid carcinomas which examined smaller numbers of thyroid cancers (21,23). The high expressions of these proteins in situ reflected the findings of their corresponding mRNAs.…”

“…ET-1 or ET A R have been only investigated at tissue levels for thyroid cancer in two research groups. Lenziardi et al studied the ET-1 in 27 patients with papillary thyroid carcinoma by immunohistochemistry and noted 90% of them expressed the protein (21). Donckier et al have shown higher expression of ET-1 and ET A R mRNA in 12 patients with papillary thyroid carcinomas than non-cancer thyroid tissues with immunohistochemistry and RT-PCR (24).…”

“…Previous studies have demonstrated that ET-1 expression is strongly correlated with neovascularization and VEGF expression via ET A R (19)(20). In papillary thyroid cancer, the role of endothelins has seldom been studied (21)(22)(23)(24). In this study, we would like to improve the understanding of angiogenesis in thyroid cancer by investigating the roles of ET-1 and its receptor ET A R in large cohort of patients with papillary thyroid carcinoma.…”

Increased expression of endothelin‐1 converting enzyme in human thyroid carcinoma

“…Endothelin‐1 (ET‐1), a 21‐amino‐acid peptide possessing vasoconstrictive and mitogenic properties, is principally released by the vascular endothelium (Yanagisawa et al ., 1988; Donckier et al ., 1991) but can also be produced by thyroid follicular cells (Lenziardi et al ., 1995). In the September 2003 issue of Clinical Endocrinology , we demonstrated that both ET‐1 mRNA and ET‐1 peptide as well as the effector receptor ET A R mRNA levels were increased in thyroid papillary carcinoma and Hashimoto's thyroiditis (Donckier et al ., 2003).…”

Immunoreactive endothelin in nodular pathology of the thyroid

“…This possible explanation would seem to be indirectly confirmed by the lack of any correlation between cystic i-ET levels and the percentage of thyrocytes and leucocytes revealed by FNA. Regarding the role of ETs in the pathogenesis of benign and malignant thyroid growth, high tissue levels of i-ET1 have recently been reported in differentiated thyroid cancers but only a slight positivity has been found in benign nodular pathology (Lenziardi et al, 1995). Our previous preliminary data show no significant difference in tissue i-ET levels between normal and benign nodular tissues from patients with differing thyroid function, thus suggesting that the role of ETs in benign thyroid growth might not be primary .…”