Genetic Diagnosis and Prophylactic Surgery for Inherited Medullary Thyroid Carcinoma

在全国范围的问卷调查中，在总共634例MTC患者中，175例男性2A型，49例FMTC型，20例男性2B型，390例散发性MTC。5年和20年生存率男性2A分别为96.9%和93.9%，FMTC分别为100%和97.1%，男性2B分别为73.8%和24.6%，散发性MTC分别为90.8%和79.0%，女性分别为94.8%和88.2%，男性分别为87.0%和60.3%(P<0.0001)，94.6%和83.1%；50岁组和50岁组分别为90.6%和81.1%(P=0.0045)。MND、FMTC、男性、≧50岁和早期患者的结果较好。47个男性2A家系中有47个突变，6个FMTC家系中有5个突变。RET原癌基因与疾病表型有关。在所有4例男性2B患者的胚系DNA中发现了918位密码子突变，在17例散发性MTC患者中有7例发现了体细胞突变。918体细胞突变患者的生存率显著低于无918突变患者(p=0.035)。早期突变检测也为MTC的手术计划提供了机会，尽管手术的适当年龄仍然存在疑问。手术时机的决定应基于密码子突变的位置和对疾病恶性程度的估计。

Out of a total of 634 MTC pts, 175 pts had MEN 2A, 49 had FMTC, 20 had MEN 2B, and 390 had sporadic MTC in a nationwide questionnaire survey. The respective 5- and 20-year survival rates were 96.9% and 93.9% in MEN 2A, 100% and 97.1% in FMTC, 73.8% and 24.6% in MEN 2B, and 90.8% and 79.0% in sporadic MTC, (p<0.05 except MEN 2A vs FMTC), 94.8% and 88.2% in women, 87.0% and 60.3% in men (p<0.0001), 94.6% and 83.1% in pts <50 years of age and 90.6% and 81.1% in pts <50 years old (p=0.0045). MND, FMTC, men, ≧50 years of age and early stage patients had a better outcome.Mutations were found in 47 of 47 MEN 2A families and five of the six FMTC families examined. RET proto-oncogene are related to the disease phenotype. A mutation at codon 918 was found in germline DNAs of all four pts with MEN 2B and somatic mutations in seven of the 17 pts sporadic MTC pts. Patients with 918 somatic mutation showed a significant lower survival rate than patients without 918 mutation (p=0.035). Early mutation detectioin also provides an opportunity to plan surgery for MTC although questions remain regarding the appropriate age of surgery. The decision as to the timing of surgery should be based on the site of the mutated codon and estimation of the degree of malignancy of the disease.