IMMUNOELECTRON MICROSCOPIC DEMONSTRATION OF REGULATED PATHWAY FOR CALCITONIN AND CONSTITUTIVE PATHWAY FOR CARCINOEMBRYONIC ANTIGEN IN THE SAME CELLS OF HUMAN MEDULLARY CARCINOMAS OF THYROID-GLANDS

The human medullary carcinomas are well known to secrete calcitonin (C T) as a neuroendocrine peptide and carcinoembryonic antigen (CEA) as a serum protein that is integrated into the cell membrane. This ultrast ructural study is designed to elucidate whether CT and CEA are secrete d via two different intracellular secretory pathways, a regulated path way and a constitutive pathway. The immunoelectron microscopic postemb edding method, performed on four cases of the human medullary carcinom as of the thyroid using plastic embedding material, disclosed two dist inct different localization patterns for CT and CEA. CT was localized exclusively in dense cored secretory granules. CEA was present in the cell membrane and in the secretory vesicles. The secretory granules we re completely negative for CEA. The trans-Golgi networks were also pos itive for CT and CEA. Electron microscopic double staining confirmed t hese localization in the same carcinoma cells, These observations sugg est the presence of two distinct pathways in the endocrine cancer cell s, i.e., the regulated pathway for CT and the constitutive pathway for CEA.