Wu Xiaohui, Xu Jun, Wang Jinhu, Gu Weizhong, Zou Chaochun
Children's Hospital of Zhejiang University School of Medicine.
Hangzhou Children's Hospital, Hangzhou, China.
Medicine (Baltimore). 2019 Nov;98(46):e17921. doi: 10.1097/MD.0000000000017921.
The aim of the study was to investigate the molecular mechanisms in childhood adrenocortical tumors (ACTs), which is still unclear.A total of 9 girls and 4 boys with ACTs were enrolled. Relevant clinical features were obtained from records. Immunohistochemistry of vimentin, chromogranin A, S100, synaptophysin, cytokeratin (CK), type 2 3β-hydroxysteroid dehydrogenase (3βHSD), cytochrome P45017α, p53, p21, p27, cyclin D1, Ki-67, insulin growth facter-2 (IGF-2), and β-catenin were undertaken for 13 tumors and 3 adjacent normal tissues. TP53 mutations in exon 2-11 were analyzed for 6 tumors and 3 blood samples.Virilization was the most common presentation (8/13, 61.5%). Immunohistochemically, p53 was positive in 8 of 13 ACTs and none in controls while p21 was positive in 12 of 13 ACTs and none in controls (P = .0036). Ki-67 was positive in 10 of 13 ACTs, but not in normal tissues (P = .0089). Although the expression of p27, cyclin D1, IGF-2 and β-catenin were similar between the ACTs and controls, β-catenin was noted in nuclear of 3 ACTs but not in controls. The difference of type 2 3βHSD and P450c17α was not significant (P > .05, respectively). Four variants of TP53 were identified in the 6 tumors. C215G variant was found in 5 of 6 while A701G and G743A variants were found in 1 case, respectively. A novel C680G variant was also noted in 1 case. It was notable that C215G variant was found in the blood mononuclear cell of 3 patients.In conclusion, p53 variant and p21 overexpression, and abnormal β-catenin distribution may be involved in the etiology and mechanism of childhood ACTs.
本研究的目的是探究儿童肾上腺皮质肿瘤（ACTs）的分子机制，目前该机制仍不清楚。总共纳入了9名患ACTs的女孩和4名患ACTs的男孩。从记录中获取相关临床特征。对13个肿瘤和3个相邻正常组织进行波形蛋白、嗜铬粒蛋白A、S100、突触素、细胞角蛋白（CK）、2型3β-羟基类固醇脱氢酶（3βHSD）、细胞色素P45017α、p53、p21、p27、细胞周期蛋白D1、Ki-67、胰岛素生长因子-2（IGF-2）和β-连环蛋白的免疫组织化学检测。对6个肿瘤和3份血液样本分析第2至11外显子中的TP53突变。男性化是最常见的表现（8/13，61.5%）。免疫组织化学检测显示，13个ACTs中有8个p53呈阳性，而对照组均为阴性；13个ACTs中有12个p21呈阳性，对照组均为阴性（P = 0.0036）。13个ACTs中有10个Ki-67呈阳性，正常组织中均为阴性（P = 0.0089）。虽然ACTs组和对照组之间p27、细胞周期蛋白D1、IGF-2和β-连环蛋白的表达相似，但3个ACTs的细胞核中发现有β-连环蛋白，而对照组未发现。2型3βHSD和P450c17α的差异无统计学意义（P均>0.05）。在6个肿瘤中鉴定出4种TP53变体。6个中有5个发现C215G变体，A701G和G743A变体各在1例中发现。还在1例中发现一种新的C680G变体。值得注意的是，3例患者的血液单核细胞中发现有C215G变体。总之，p53变体和p21过表达以及β-连环蛋白分布异常可能参与儿童ACTs的病因和发病机制。
