The goals are to improve methods of early detection of medullary thyroid cancer (MTC) and to determine the optimum protocol for surveillance of relatives of patients with this neoplasm. Thorough calcitonin (CT) studies of the families of all patients with MTC have allowed identification of 29 patients with the sporadic type and 86 patients from 19 families with the dominantly inherited MTC. The hereditary disease is characterized by an earlier age of onset, a shorter life expectancy unless discovered early by CT studies, and an association with parathyroid adenomas and pheochromocytomas as a part of the multiple endocrine neoplasia syndrome type 2. Recent studies have shown that the two types may be distinguished pathologically by the presence of C-cell hyperplasia distal to the malignancy only in the hereditary type. This not only has clinical importance but also has theoretical importance in providing evidence for the two-mutational-event theory on the initiation of cancer. Many patients have been identified as having residual malignancy postoperatively. These residual tumors have not generally been completely resectable by further surgery, and other treatment possibilities are being explored. The cause of the rapid growth of MTC in the mucosal neuroma phenotype patients (MEN-2b) is being investigated. Our present data demonstrate that 19 affected individuals in the nine of 10 MEN-2a families studied and five affected individuals from three of five MEN-2b families studied carry a minute but visible deletion of chromosome 20 (no deletion was found in four patients from four MEN-1 kindreds). Chromosome studies are being extended to determine the proportion of families in whom this deletion is observable and the relationship of its presence and its size to the various manifestations of endocrine neoplasia syndromes. Localization of this gene to chromosome 20 will facilitate the determination of its linkage to various marker genes including DNA restriction fragments. (2)
