Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, Zhejiang Province, China.
Fam Cancer. 2012 Jun;11(2):157-65. doi: 10.1007/s10689-011-9501-7.
Hereditary medullary thyroid carcinoma (hereditary MTC) is a rare malignancy, accounting for 25-30% of all MTC. It occurs as part of multiple endocrine neoplasia type 2 (MEN 2). Autosomal dominant gain-of-function mutations in the RET proto-oncogene is the cause of the disease, in which the common mutations are codons 609, 611, 618, 620, 630, 634 and 918. In recent years, the spectrum of RET gene mutations has changed. The classical mutations reduced, whereas the less aggressive mutations increased. Hereditary MTC is a time-dependent disease. Stages of the disorder at diagnosis can significantly influence survival rates. Based on the genotype-phenotype, RET mutations have been classified into four risk levels by American Thyroid Association (ATA) at 2009. The classification system guides the hereditary MTC management, including risk assessment, biochemical screenings and surgical intervention. Though the application of genetic testing and codon-specific phenotypes in hereditary MTC diagnosis is effective with high accuracy, there are some difficulties in implementing RET gene testing as a routine for MTC diagnosis. And most of carriers with RET mutations did not undergo thyroidectomy at the age recommended by the ATA guidelines. The aim of the study is to review the hereditary MTC and discuss the management dilemma.
遗传性髓样甲状腺癌（hereditary MTC）是一种罕见的恶性肿瘤，占所有 MTC 的 25-30%。它是多发性内分泌肿瘤 2 型（MEN 2）的一部分。RET 原癌基因的常染色体显性获得性功能突变是该病的病因，常见的突变位于密码子 609、611、618、620、630、634 和 918。近年来，RET 基因突变谱发生了变化。经典突变减少，而侵袭性较低的突变增加。遗传性 MTC 是一种与时间相关的疾病。诊断时疾病的分期可显著影响生存率。基于基因型-表型，美国甲状腺协会（ATA）在 2009 年将 RET 突变分为四个风险级别。该分类系统指导遗传性 MTC 的管理，包括风险评估、生化筛查和手术干预。尽管遗传检测和密码子特异性表型在遗传性 MTC 诊断中的应用具有很高的准确性，但在将 RET 基因检测作为 MTC 诊断的常规方法实施方面存在一些困难。并且，大多数携带 RET 突变的患者并未按照 ATA 指南建议的年龄进行甲状腺切除术。本研究旨在回顾遗传性 MTC，并讨论管理困境。
