Genetic Diagnosis and Prophylactic Surgery for Inherited Medullary Thyroid Carcinoma

在一项全国性问卷调查中，在总共634名MTC患者中，175名患者患有MEN 2A，49名患者患有FMTC，20名患者患有MEN 2B，390名患者患有散发性MTC。MEN 2A的5年和20年生存率分别为96.9%和93.9%，FMTC为100%和97.1%，MEN 2B为73.8%和24.6%，散发性MTC为90.8%和79.0%。（除MEN 2A与FMTC外，p<0.05），女性为94.8%和88.2%，男性为87.0%和60.3%（p<0.0001），50岁以下患者分别为94.6%和83.1%，50岁以下患者分别为90.6%和81.1%（p=0.0045）。MND、FMTC、男性、> 50岁及早期患者预后较好，47个MEN 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名MEN 2B患者的生殖系DNA中发现了密码子918处的突变，在17名散发性MTC患者中的7名患者中发现了体细胞突变。有918体细胞突变的患者的生存率显著低于无918突变的患者（p=0.035）。早期突变检测也为MTC的手术计划提供了机会，尽管关于手术的适当年龄仍存在问题。手术时机的决定应根据突变密码子的位置和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.