University of Michigan, Ann Arbor, MI, USA.
J Clin Oncol. 2013 Aug 20;31(24):3012-8. doi: 10.1200/JCO.2012.48.0988. Epub 2013 Jul 22.
Adrenocortical carcinoma (ACC) is an endocrine malignancy with a poor prognosis. The association of adult-onset ACC with inherited cancer predisposition syndromes is poorly understood. Our study sought to define the prevalence of Lynch syndrome (LS) among patients with ACC.
One hundred fourteen patients with ACC were evaluated in a specialized endocrine oncology clinic and were prospectively offered genetic counseling and clinical genetics risk assessment (group 1). In addition, families with known mismatch repair (MMR) gene mutations that were recorded in the University of Michigan Cancer Genetics Registry were retrospectively reviewed for the presence of ACC (group 2). ACC tumors from patients with LS were tested for microsatellite instability and immunohistochemistry (IHC) to evaluate for MMR deficiency.
Ninety-four (82.5%) of 114 patients with ACC underwent genetic counseling (group 1). Three individuals (3.2%) had family histories suggestive of LS. All three families were found to have MMR gene mutations. Retrospective review of an additional 135 MMR gene-positive probands identified two with ACC (group 2). Four ACC tumors were available (group 1, 3; group 2, 1). All four tumors were microsatellite stable; three had IHC staining patterns consistent with germline mutation status.
The prevalence of LS among patients with ACC is 3.2%, which is comparable to the prevalence of LS in colorectal and endometrial cancer. Patients with ACC and a personal or family history of LS tumors should be strongly considered for genetic risk assessment. IHC screening of all ACC tumors may be an effective strategy for identifying patients with LS.
肾上腺皮质癌（ACC）是一种预后不良的内分泌恶性肿瘤。成人发病的 ACC 与遗传性癌症易感性综合征的关系尚未被充分认识。我们的研究旨在确定 Lynch 综合征（LS）在 ACC 患者中的患病率。
114 例 ACC 患者在一家内分泌肿瘤学专科诊所接受评估，并前瞻性地提供遗传咨询和临床遗传学风险评估（第 1 组）。此外，还回顾性地审查了密歇根大学癌症遗传学登记处记录的已知存在错配修复（MMR）基因突变的家族中是否存在 ACC（第 2 组）。LS 患者的 ACC 肿瘤进行微卫星不稳定性和免疫组化（IHC）检测，以评估 MMR 缺陷。
114 例 ACC 患者中有 94 例（82.5%）接受了遗传咨询（第 1 组）。3 例（3.2%）有提示 LS 的家族史。所有 3 个家族均发现存在 MMR 基因突变。对另外 135 例 MMR 基因突变阳性先证者的回顾性研究发现 2 例有 ACC（第 2 组）。共有 4 例 ACC 肿瘤可供研究（第 1 组 3 例，第 2 组 1 例）。所有 4 例肿瘤的微卫星均稳定；3 例 IHC 染色模式与种系突变状态一致。
ACC 患者中 LS 的患病率为 3.2%，与结直肠癌和子宫内膜癌的 LS 患病率相当。有 ACC 个人或家族史的 LS 肿瘤患者应强烈考虑进行遗传风险评估。对所有 ACC 肿瘤进行 IHC 筛查可能是识别 LS 患者的有效策略。
