Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109-5419, USA.
J Clin Endocrinol Metab. 2013 Jan;98(1):E119-25. doi: 10.1210/jc.2012-2198. Epub 2012 Nov 21.
Adrenocortical carcinoma (ACC) is a hallmark cancer in families with Li Fraumeni syndrome (LFS) caused by mutations in the TP53 gene. The prevalence of germline TP53 mutations in children diagnosed with ACC ranges from 50-97%. Although existing criteria advocate for TP53 testing in all patients with ACC regardless of age at diagnosis, the overall prevalence of germline mutations in patients diagnosed with ACC has not been well studied.
A total of 114 patients with confirmed ACC evaluated in the University of Michigan Endocrine Oncology Clinic were prospectively offered genetic counseling and TP53 genetic testing, regardless of age at diagnosis or family history. Ninety-four of the 114 patients met with a genetic counselor (82.5%), with 53 of 94 (56.4%) completing TP53 testing; 9.6% (nine of 94) declined testing. The remainder (32 of 94; 34%) expressed interest in testing but did not pursue it for various reasons.
Four of 53 patients in this prospective, unselected series were found to have a TP53 mutation (7.5%). The prevalence of mutations in those diagnosed over age 18 was 5.8% (three of 52). There were insufficient data to estimate the prevalence in those diagnosed under age 18. None of these patients met clinical diagnostic criteria for classic LFS. Three of the families met criteria for Li Fraumeni-like syndrome; one patient met no existing clinical criteria for LFS or Li Fraumeni-like syndrome. Three of the four patients with mutations were diagnosed with ACC after age 45.
Genetic counseling and germline testing for TP53 should be offered to all patients with ACC. Restriction on age at diagnosis or strength of the family history would fail to identify mutation carriers.
肾上腺皮质癌（ACC）是 Li Fraumeni 综合征（LFS）家族的标志性癌症，由 TP53 基因突变引起。在诊断为 ACC 的儿童中，种系 TP53 突变的患病率为 50-97%。尽管现有标准主张对所有 ACC 患者进行 TP53 检测，无论其诊断时的年龄如何，但尚未很好地研究诊断为 ACC 的患者中种系突变的总体患病率。
在密歇根大学内分泌肿瘤学诊所，共前瞻性地为 114 例确诊的 ACC 患者提供了遗传咨询和 TP53 基因检测，无论其诊断时的年龄或家族史如何。114 例患者中有 94 例（82.5%）与遗传咨询师会面，其中 53 例（56.4%）完成了 TP53 检测；94 例中有 9 例（9.6%）拒绝检测。其余（94 例中的 32 例；34%）表示有检测的兴趣，但由于各种原因没有进行检测。
在这个前瞻性的、未选择的系列中，有 4 例患者（53 例中的 7.5%）发现 TP53 突变。在诊断年龄超过 18 岁的患者中，突变的患病率为 5.8%（52 例中的 3 例）。在诊断年龄小于 18 岁的患者中，尚不足以估计其患病率。这些患者均不符合经典 Li Fraumeni 综合征的临床诊断标准。其中 3 个家族符合 Li Fraumeni 样综合征的标准；1 例患者不符合 Li Fraumeni 综合征或 Li Fraumeni 样综合征的任何现有临床标准。这 4 例突变患者中有 3 例在 45 岁以后被诊断为 ACC。
应向所有 ACC 患者提供遗传咨询和 TP53 种系检测。限制在诊断年龄或家族史的强度上，将无法识别突变携带者。
