Peptidylglycine α-amidating monooxygenase in neuroendocrine tumors: Its identification, characterization, quantification, and relation to the grade of morphologic differentiation, amidated peptide content, and granin immunocytochemistry

One hundred forty-seven human neuroendocrine tumors were immunocytochemically screened with antibodies directed against several portions of peptidylglycine α-amidating monooxygenase, the enzyme responsible for the amidation of neurohormonal peptides. A subset of 23 tumors was then studied by enzyme assay and immunoblotting. Although the enzyme was present in all neuroendocrine cell types, the specimens with the highest content were from well-differentiated tumors known to produce amidated peptides, such as intestinal and bronchial carcinoids, gastrinomas, medullary thyroid carcinomas, and pancreatic polypeptide-producing tumors. A high enzyme content also was observed in well-differentiated tumors not known to contain amidated products (e.g., gastric carcinoids). A good correlation was observed between staining intensity of the enzyme on protein blots and immunocytochemical signal. Tumor-specific differences in cleavage of the less active high-molecular-weight forms may contribute to discrepancies between enzyme activity level and immunochemical expression. Although no clear-cut association was found between enzyme immunoreactivity and expression of a single granin, canonic secretory granule markers, all enzyme-reactive tumors were found to contain high levels of at least one of the three granins (chromogranin A, chromogranin B, or secretogranin II).