Familial Adrenocortical Carcinoma in Association With Lynch Syndrome.
Familial Adrenocortical Carcinoma in Association With Lynch Syndrome.
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DOI：
10.1210/jc.2016-1460
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发表时间：
2016-06
期刊：
影响因子：
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通讯作者：
Gurnell M
中科院分区：
文献类型：
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作者：
Challis BG;Kandasamy N;Powlson AS;Koulouri O;Annamalai AK;Happerfield L;Marker AJ;Arends MJ;Nik-Zainal S;Gurnell M
肾上腺皮质癌(ACC)是一种罕见的内分泌恶性肿瘤，预后不良。虽然大多数儿童ACC发生在遗传性癌症易感综合征的背景下，但是否存在遗传性肿瘤易感性对成人ACC的发展尚不清楚。在这里，我们报告了家族性ACC首次出现在由致病种系MSH2突变引起的林奇综合征一家系中。一位54岁女性，有卵巢和结直肠恶性肿瘤的病史，被发现患有ACC。详细的家族史显示，她的母亲死于癌症，她的妹妹之前被诊断出患有子宫内膜癌和结直肠癌。我们考虑了Lynch综合征的统一诊断，免疫组织化学分析显示MSH2和MSH6在AAC(先证者和她的母亲)和她姐姐的子宫内膜癌中都没有表达。随后的基因筛查证实，先证者和她的姐妹中存在种系MSH2突变(导致外显子1-3缺失)。我们的发现有力地支持了最近的提议，即ACC应该被认为是林奇综合征相关的肿瘤，并包括在阿姆斯特丹II临床诊断标准中。我们还建议，在针对DNA错配修复基因发生胚系突变的个体的癌症监测策略中，应考虑对ACC进行筛查。这项研究首次描述了由生殖系MSH2突变引起的林奇综合征家系的代际发生的ACC。因此，ACC应该包括在LS的临床诊断标准中，并考虑在对DNA错配修复基因发生胚系突变的个体的癌症监测建议中。
Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a poor prognosis. Although the majority of childhood ACC arises in the context of inherited cancer susceptibility syndromes, it remains less clear whether a hereditary tumor predisposition exists for the development of ACC in adults. Here, we report the first occurrence of familial ACC in a kindred with Lynch syndrome resulting from a pathogenic germline MSH2 mutation. A 54-year-old female with a history of ovarian and colorectal malignancy was found to have an ACC. A detailed family history revealed her mother had died of ACC and her sister had previously been diagnosed with endometrial and colorectal cancers. A unifying diagnosis of Lynch syndrome was considered, and immunohistochemical analyses demonstrated loss of MSH2 and MSH6 expression in both AACs (proband and her mother) and in the endometrial carcinoma of her sister. Subsequent genetic screening confirmed the presence of a germline MSH2 mutation (resulting in deletions of exons 1–3) in the proband and her sister. Our findings provide strong support for the recent proposal that ACC should be considered a Lynch syndrome-associated tumor and included in the Amsterdam II clinical diagnostic criteria. We also suggest that screening for ACC should be considered in cancer surveillance strategies directed at individuals with germline mutations in DNA mismatch repair genes. This study provides the first description of an intergenerational occurrence of ACC in a family with Lynch Syndrome resulting from a germline MSH2 mutation. Thus, ACC should be included in clinical diagnostic criteria for LS and considered in cancer surveillance recommendations for individuals with germline mutations in DNA mismatch repair genes.