Increased expression of endothelin-1 and its mitogenic receptor ETA in human papillary thyroid carcinoma.
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.


METHODS
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 (ETAR and ETBR).


RESULTS
ET-1 and ETAR 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 ETBR was unaltered. In Hashimoto's thyroiditis, ET-1 and ETAR 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 ETAR overexpression observed in thyroid carcinoma suggest a mitogenic role of ET-1 that theoretically could be countered by ETAR antagonists. ET-1 and ETAR overexpression in thyroiditis supports a role of ET-1 in the inflammatory process.
Donckier
Julian E
JE
Department of Internal Medicine, University Hospital of Mont-Godinne, Université Catholique de Louvain, B-5530 Yvoir, Belgium. Julian.Donckier@mint.ucl.ac.be
Michel
Luc
L
Van Beneden
Ronald
R
Delos
Monique
M
Havaux
Xavier
X
D000293:Adolescent; D000328:Adult; D000368:Aged; D002291:Carcinoma, Papillary / Q000378:metabolism*; D019332:Endothelin-1 / Q000032:analysis* / Q000235:genetics; D005260:Female; D006044:Goiter, Nodular / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D017466:Receptors, Endothelin / Q000032:analysis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000378:metabolism*; D013967:Thyroiditis, Autoimmune / Q000378:metabolism
D019332:Endothelin-1; D012333:RNA, Messenger; D017466:Receptors, Endothelin