Immunohistochemical localization of endothelin-converting enzyme-1 in neuroendocrine tumors and normal human tissue.

Endothelin-converting enzyme-1 (ECE-1) is the key enzyme of endothelin biosynthesis, catalyzing the final step in the process. In this study, we investigated the cellular distribution of ECE-1 in 19 normal human tissues and 16 neuroendocrine tumors using immunohistochemical staining with antigen retrieval. ECE-1 was expressed in vessel endothelial cells as well as nearly all epithelial cells, glands and duct cells in normal human tissues including the esophagus, stomach, small intestine, appendix, colon, liver, gallbladder, pancreas, endometrium, cervix, breast, skin, prostate, urinary bladder, lung, kidney, sympathetic ganglion, thyroid gland, and adrenal gland. The most interesting finding was that ECE-1 was expressed in normal neuroendocrine cells. ECE-1 was also expressed in all 16 neuroendocrine tumors, including three paragangliomas, five pheochromocytomas, three carcinoid tumors, four medullary carcinomas of the thyroid, and one islet cell tumor of the pancreas. In conclusion, ECE-1 is enriched in neuroendocrine cells and neuroendocrine tumors, suggesting an important biologic role for the enzyme in the neuroendocrine system.