VERY EARLY DETECTION OF RET PROTO-ONCOGENE MUTATION IS CRUCIAL FOR PREVENTIVE THYROIDECTOMY IN MULTIPLE ENDOCRINE NEOPLASIA TYPE 2 CHILDREN.

GABRIELA SANSÓ; HORACIO DOMENÉ; MARIA GARCIA RUDAZ; EDUARDO PUSIOL; ANA K. DE MONDINO; MARIA ROQUE; ALEJANDRO RING; HECTOR PERINETTI; BORIS ELSNER; SONIA IORSCANSKY; MARTA BARONTINI

CANCER

JOHN WILEY & SONS INC

Lugar: New York; Año: 2002 vol. 94 p. 323 - 330

0008-543X

 Abstract Background: Multiple endocrine neoplasia type 2 (MEN 2) is an inherited disease caused by germline mutations in the RET proto-oncogene, and responsible for the development of endocrine neoplasia. Its prognosis is dependent on the appearance and spread of medullary thyroid carcinoma (MTC). Relatives at risk can be identified before clinical or biochemical signs of the disease become evident. Patients and Methods: Twenty-one families with MEN 2 (16 MEN 2A and 5 MEN 2B) were studied. Peripheral blood DNA was amplified by polymerase chain reaction (PCR). DNA sequence or restriction enzyme analysis was performed to detect mutations of RET proto-oncogene exons 10, 11, 16. Molecular analysis was carried out in all index cases as well as in 98 relatives of MEN 2A patients (60 juveniles, aged 6 months to 21 ears. and 38 adults, aged 22 to 81 ears.) and in 13 relatives from MEN 2B families. Results: Molecular studies showed a mutation at codon 634 exon 11 in all MEN 2A patients. All MEN 2B patients showed an ATG®ACG (Met918Thr) mutation. In MEN 2A families 42/98 relatives were affected. Total thyroidectomy was performed in 18 juvenile carriers aged 17 months to 21 years old. Histopathologic studies of the glands revealed C-cell hyperplasia in all of them, medullary thyroid carcinoma (MTC) in 15, only one of them with lymph node metastases. Conclusions: The consistent finding of C-cell disease in all the juvenile carriers who underwent preventive thyroidectomy emphasizes the relevance of early screening in children at risk of developing MTC. The presence of MTC in the specimen of prophylactic thyroidectomy from a 17- month old girl highlights the importance of thyroidectomy as soon as the molecular diagnosis is confirmed.