title: Immunohistochemical localization of endothelin-1, endothelin-3 and endothelin receptors in human pheochromocytoma and paraganglioma.
abstract: Endothelin (ET) and its receptor system have been shown to exert various biological effects on different types of cells in addition to their well-known vasoconstrictor activity. Recently ET-1, ET-3 and the ETB receptor have been shown to play an important role in the development of neural crest-derived cells and, in this context, pheochromocytomas have been reported to harbor ET-1. Endothelin-3 or ET receptor subtypes, however, have not been examined in pheochromocytoma and paraganglioma so far. In the present study the immunohistochemical localization of ET-1/big ET-1, ET-3/big ET-3 and the ETA and ETB receptors were investigated to clarify the biological characteristics of these two tumors using 32 pheochromocytomas and 11 extra-adrenal paragangliomas. Endothelin-1/big ET-1 was detected in 19 pheochromocytomas (59%) and eight paragangliomas (72%), while ET-3/big ET-3 was detected in 10 pheochromocytomas (31%) and three paragangliomas (27%). The ETA receptor was found in 21 pheochromocytomas (66%) and in eight paragangliomas (73%), while the ETB receptor was found in 25 pheochromocytomas (78%) and in eight paragangliomas (73%). Normal adrenomedullary cells lacked each antigen examined. Endothelin-immunoreactive tumor cells were distributed focally or in a manner scattered, while receptor-immunostained tumor cells were distributed with a focal pattern for the ETA receptor and with a focal or diffuse pattern for the ETB receptor. Endothelin and its receptor coexisted in the same tumor in 21 of 28 ET-positive pheochromocytomas and in eight of 10 ET-positive paragangliomas. In addition, seven pheochromocytomas and two paragangliomas revealed positivity of the receptor(s) irrespective of the absence of ET-immunoreactivity. In conclusion, ET and its receptor are frequently and concomitantly expressed in the pheochromocytoma and paraganglioma. From the highly frequent expression of this system or the receptor(s), ET-receptor-mediated signal transduction of these tumors concerning growth and/or cell survival is expected, although definite biological significance of this ligand-receptor system in these tumors awaits further investigation.
authors.affiliation: Department of Pathology, Fukushima Medical College, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Watanabe
authors.forename: H
authors.initials: H
authors.lastname: Hiraki
authors.forename: H
authors.initials: H
authors.lastname: Hasegawa
authors.forename: T
authors.initials: T
authors.lastname: Tanigawa
authors.forename: I
authors.initials: I
authors.lastname: Emura
authors.forename: K
authors.initials: K
authors.lastname: Honma
authors.forename: H
authors.initials: H
authors.lastname: Shibuya
authors.forename: T
authors.initials: T
authors.lastname: Fukuda
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000737:chemistry*; D019332:Endothelin-1 / Q000032:analysis*; D019334:Endothelin-3 / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D009363:Neoplasm Proteins / Q000032:analysis*; D010235:Paraganglioma / Q000737:chemistry*; D010673:Pheochromocytoma / Q000737:chemistry*; D017466:Receptors, Endothelin / Q000032:analysis*
chemical_list: D019332:Endothelin-1; D019334:Endothelin-3; D009363:Neoplasm Proteins; D017466:Receptors, Endothelin