The discovery of the ret proto-oncogene in 1993 demonstrates the influence of genetic testing on clinical practice. A germline mutation in the RET gene, which is located on chromosome 10, leads to an alteration of the transmembrane tyrosine kinase receptor, which is expressed primarily in neuroendocrine and neural cells. A patient with this genotype phenotypically can express several disease states that include medullary thyroid cancer (MTC), hyperparathyroidism, pheochromocytoma, and, less commonly, Hirschsprung's disease and cutaneous lichen amyloidosis. The expression of “inheritable” MTC occurs in the context of multiple endocrine neoplasia (MEN) II A, MEN II B, and familial MTC. The eventual neoplastic transformation of normal thyroid parafollicular C-cells to C-cell hyperplasia (CCH), and MTC occurs with 100% penetrance in patients with a germline mutation in the RET gene. This definitive pattern of expression should allow for prophylactic surgical intervention before the formation of MTC. The issue is when to perform thyroidectomy in patients with this tumor, because the procedure is technically more demanding and prone to complications the younger the patient, but the risk of tumor transformation or dissemination increases while waiting.
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Accepted: June 17, 2003
© 2004 Elsevier Inc. Published by Elsevier Inc. All rights reserved.