Sanso Gabriela E, Domene Horacio M, Garcia RudazMariaC, Pusiol Eduardo, de MondinoAnaK, Roque Maria, Ring Alejandro, Perinetti Hector, Elsner Boris, Iorcansky Sonia, Barontini Marta
Centro de Investgaciones Endocrinológicas, Hospital de Niños R. Gutiérrez, Buenos Aires, Argentina.
Cancer. 2002 Jan 15;94(2):323-30. doi: 10.1002/cncr.10228.
Multiple endocrine neoplasia type 2 (MEN 2) is an inherited disease caused by germline mutations in the RET proto-oncogene, and is 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.
Twenty-one families with MEN 2 (16 families with MEN 2A and 5 families with MEN 2B) were studied. Peripheral blood DNA was amplified by polymerase chain reaction. DNA sequence or restriction enzyme analysis was performed to detect mutations of RET proto-oncogene exons 10, 11, and 16. Molecular analysis was carried out in all index patients as well as in 98 relatives of MEN 2A patients (60 juveniles, ages 6 months to 21 years, and 38 adults, ages 22 to 81 years) and in 13 relatives (6 juveniles ages 10 to 21 years, and 7 adults ages 41 to 66 years) from MEN 2B families.
Molecular studies showed a mutation at codon 634, exon 11 in all MEN 2A patients. All MEN 2B patients showed an ATG to ACG (Met918Thr) mutation. In MEN 2A families, 42 out of 98 relatives were affected. Total thyroidectomy was performed in 18 juvenile carriers ages 17 months to 21 years. Histopathologic studies of the glands revealed parafollicular cell (C-cell) hyperplasia in all of these carriers, medullary thyroid carcinoma in 15 carriers, and only one carrier with lymph node metastases.
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.
2型多发性内分泌腺瘤病（MEN 2）是一种由RET原癌基因种系突变引起的遗传性疾病，可导致内分泌肿瘤的发生。其预后取决于甲状腺髓样癌（MTC）的出现和扩散。在疾病的临床或生化体征出现之前，就可以识别出有风险的亲属。
对21个MEN 2家族（16个MEN 2A家族和5个MEN 2B家族）进行了研究。通过聚合酶链反应扩增外周血DNA。进行DNA序列或限制性酶切分析以检测RET原癌基因第10、11和16外显子的突变。对所有索引患者以及98名MEN 2A患者的亲属（60名青少年，年龄6个月至21岁，38名成年人，年龄22至81岁）和13名MEN 2B家族的亲属（6名青少年，年龄10至21岁，7名成年人，年龄41至66岁）进行了分子分析。
分子研究显示，所有MEN 2A患者的第11外显子密码子634处均有突变。所有MEN 2B患者均表现出ATG到ACG（Met918Thr）突变。在MEN 2A家族中，98名亲属中有42名受影响。对18名年龄在17个月至21岁的青少年携带者进行了全甲状腺切除术。对腺体的组织病理学研究显示，所有这些携带者均有滤泡旁细胞（C细胞）增生，15名携带者有甲状腺髓样癌，只有1名携带者有淋巴结转移。
在所有接受预防性甲状腺切除术的青少年携带者中均发现C细胞疾病，这强调了对有发生MTC风险的儿童进行早期筛查的重要性。一名17个月大女孩的预防性甲状腺切除标本中存在MTC，这突出了在分子诊断得到证实后尽快进行甲状腺切除术的重要性。
