Predictive molecular genetics in the diagnosis and treatment of families with multiple endocrine neoplasia type 2

Background and objective: When multiple endocrine neoplasia type 2 (MEN2) i s suspected, genetic tests are at the centre of screening procedures. It wa s the aim of this study to compare the diagnostic value of molecular biolog ical investigations with that of conventional biochemical tests. Patients and methods: The study cohort consisted of all 144 patients cared for in our department since 1990 with the suspected diagnosis of MEN2 (evid ence of a medullary thyroid carcinoma [MTC]), coexistence of two MEN2 tumou rs or a family history of MEN2, 14 of the 144 patients (from 12 families) w ere already known to have an hereditary MTC, while the remaining 130 had be en referred for further diagnostic investigations. Results: An hereditary MTC was diagnosed in 22 of the 1 30 patients, a spor adic MTC in 32, while no definitive classification was possible in 20 MTC p atients without a positive family history and on whom no mutation analysis had been performed, MEN2 was excluded in 56 family members. All 22 patients with newly diagnosed MTC had abnormally high calcitonin levels, A germ-lin e mutattion in the RET proto-oncogene was found in 8 of the 9 families who had undergone molecular biological tests. The investigate results led to a thyroidectomy in 19 of the 22 patients with hereditary MTC: in all of them the surgical specimen showed C-cell hyperplasia and/o MTC. Conclusion: These results emphasize the importance of genetic tests in fami ly screening. Preoperative measurement of calcitonin remains essential in M EN2 families in whom a germ-line mutation is not known. The choice of the a ppropriate diagnostic test must be individualized to the particular patient s so that optimal results are obtained.