Biallelic APC Inactivation Was Responsible for Functional Adrenocortical Adenoma in Familial Adenomatous Polyposis with Novel Germline Mutation of the APC Gene: Report of a Case
Biallelic APC Inactivation Was Responsible for Functional Adrenocortical Adenoma in Familial Adenomatous Polyposis with Novel Germline Mutation of the APC Gene: Report of a Case
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DOI：
10.1093/jjco/hyp093
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发表时间：
2009-12-01
影响因子：
2.4
通讯作者：
Sakai, Yoshiharu
中科院分区：
文献类型：
--
作者：
Hosogi, Hisahiro;Nagayama, Satoshi;Sakai, Yoshiharu
家族性腺瘤性息肉病（FAP）患者会出现各种结肠外病变，其中功能性肾上腺皮质肿瘤很少见。一名 44 岁女性因中间型 FAP 导致晚期升结肠癌双侧卵巢转移引起假梅格斯综合征而住院。此外，检测到双侧肾上腺皮质腺瘤，功能分析显示与库欣综合征一致的激素分泌模式。她接受了右半结肠切除术并摘除双侧卵巢。术后 10 个月，由于没有检测到转移病灶，残余的结直肠和较大的左侧肾上腺被切除，激素分泌过多恢复正常。对腺瘤性结肠息肉病 (APC) 基因的直接测序揭示了癌组织中密码子 1577 处的无义种系突变和密码子 554 处的额外无义体细胞突变。由于正常等位基因缺失导致的双等位基因 APC 失活在肾上腺皮质腺瘤中很明显。在 APC 启动子区域未检测到高甲基化的 CpG 岛。 β-连环蛋白的免疫染色显示在包括肾上腺皮质腺瘤在内的切除组织中存在弥漫性细胞质表达。双等位基因 APC 失活可能在 FAP 患者发生皮质醇分泌性肾上腺皮质腺瘤中发挥作用。值得注意的是，同一个体的不同肿瘤中双等位基因 APC 失活是以不同方式引起的。
Familial adenomatous polyposis (FAP) patients develop various extracolonic lesions, among which functional adrenocortical neoplasms are infrequent. A 44-year-old woman was hospitalized because of pseudo-Meigs' syndrome, caused by bilateral ovarian metastases from an advanced ascending colon cancer due to FAP of intermediate type. Furthermore, bilateral adrenocortical adenomas were detected, and functional analyses showed a hormonal secretion pattern consistent with Cushing's syndrome. She underwent a right hemicolectomy with extirpation of bilateral ovaries. At 10 months post-operative with no detectable metastatic lesions, the residual colorectum and the larger, left adrenal gland were resected, and the hormonal hypersecretion was normalized. Direct sequencing of the adenomatous polyposis coli (APC) gene revealed a nonsense germline mutation at codon 1577 and an additional nonsense somatic mutation at codon 554 in cancer tissues. Biallelic APC inactivation due to loss of the normal allele was evident in the adrenocortical adenoma. There were no hypermethylated CpG islands detected in APC promoter regions. Immunostaining for beta-catenin revealed diffuse cytoplasmic expression in resected tissues including adrenocortical adenoma. Biallelic APC inactivation may play a role in developing cortisol-secreting adrenocortical adenoma in FAP patients. It is noteworthy that biallelic APC inactivation was caused in different ways in different tumors from the same individual.