Purpose The clinical features, pathogenesis, and outcomes in children with adrenocortical tumors (ACTs) without germline TP53 mutations have not been systematically studied. Herein, we describe these correlates and analyze their association with outcome. Patients and Methods Genomic DNA was analyzed for TP53, CTNNB1, CDKN1C, ATRX, and chromosome 11p15 abnormalities. β-catenin expression and Ki-67 labeling index (LI) were evaluated by immunostaining. Primary end points were progression-free (PFS) and overall survival. Results Median age of 42 girls and 18 boys was 3.3 years (range, 0.25 to 21.7 years). Complete resection (stages I and II) was achieved in 32 patients, and 28 patients had stage III or IV disease. Constitutional abnormalities of chromosome 11p15 occurred in nine of 40 patients, with six patients not showing phenotype of Beckwith-Wiedemann syndrome. Three-year PFS and overall survival for all patients were 71.4% and 80.5%, respectively. In single-predictor Cox regression analysis, age, disease stage, tumor weight, somatic TP53 mutations, and Ki-67 LI were associated with prognosis. Ki-67 LI and age remained significantly associated with PFS after adjusting for stage and tumor weight. Three-year PFS for 27 patients with Ki-67 LI ≥ 15% was 48.5% compared with 96.2% for 29 patients with Ki-67 LI < 15% (log-rank P = .002), and the rate of relapse increased by 24% with each 1-year increase in age at diagnosis (hazard ratio, 1.24; P = .0057). Conclusion Clinicopathologic features and outcomes of children with ACTs without germline TP53 mutations overlapped those reported for children with germline TP53 mutations. Our findings highlight the central role of genetic or epigenetic alterations on chromosome 11p15 in pediatric ACTs. Ki-67 LI is a strong prognostic indicator and should be investigated to improve the histologic classification of pediatric ACTs.

中文翻译：

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确定与无生殖系 TP53 突变的肾上腺皮质肿瘤儿童结局相关的临床和生物学相关性：圣裘德肾上腺皮质肿瘤登记处和儿童肿瘤学组研究

目的 尚未系统研究无生殖系 TP53 突变的肾上腺皮质肿瘤 (ACTs) 儿童的临床特征、发病机制和结果。在此，我们描述了这些相关性并分析了它们与结果的关联。患者和方法 分析基因组 DNA 的 TP53、CTNNB1、CDKN1C、ATRX 和染色体 11p15 异常。通过免疫染色评估 β-连环蛋白表达和 Ki-67 标记指数 (LI)。主要终点是无进展（PFS）和总生存期。结果 42 名女孩和 18 名男孩的中位年龄为 3.3 岁（范围 0.25 至 21.7 岁）。32 名患者实现了完全切除（I 期和 II 期），28 名患者患有 III 期或 IV 期疾病。40 名患者中有 9 名发生了染色体 11p15 的体质异常，六名患者没有表现出 Beckwith-Wiedemann 综合征的表型。所有患者的三年 PFS 和总生存率分别为 71.4% 和 80.5%。在单预测因子 Cox 回归分析中，年龄、疾病分期、肿瘤重量、体细胞 TP53 突变和 Ki-67 LI 与预后相关。在调整分期和肿瘤重量后，Ki-67 LI 和年龄仍然与 PFS 显着相关。Ki-67 LI ≥ 15% 的 27 名患者的三年 PFS 为 48.5%，而 Ki-67 LI < 15% 的 29 名患者的三年 PFS 为 96.2%（对数秩 P = .002），并且复发率增加了24%，诊断时年龄每增加 1 年（风险比，1.24；P = .0057）。结论 无胚系 TP53 突变的 ACT 儿童的临床病理特征和结果与报告的具有胚系 TP53 突变的儿童的临床病理特征和结果重叠。我们的研究结果强调了染色体 11p15 上遗传或表观遗传改变在儿科 ACT 中的核心作用。Ki-67 LI 是一个强有力的预后指标，应进行研究以改进儿科 ACT 的组织学分类。