Unidade de Suprarrenal e Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular LIM-42, Hospital das Clínicas e, Brazil.
Mol Cell Endocrinol. 2012 Mar 31;351(1):52-7. doi: 10.1016/j.mce.2011.09.040. Epub 2011 Oct 14.
Adrenocortical carcinoma (ACC) is a rare malignancy with poor prognosis. The incidence of pediatric adrenocortical tumors (ACT) is remarkably high in Southern Brazil, where it is estimated to be 15 times greater than the world occurrence, due to a high frequency of a germline mutation (p.R337H) of the TP53 gene. Differently from adults, pediatric adrenocortical neoplasms with apparently poor prognosis based on histopathological features have often a good clinical outcome. A high Weiss score is definitely not a good predictor of survival in children, but it is much more discriminative of a poor outcome in adult tumors. Besides important differences in prognosis, adrenocortical tumorigenesis has distinct patterns between children and adults. In this review, we summarize recent data from ours and other Institutions, showing that the prognostic importance of molecular markers is striking different between pediatric and adult ACT. Although the majority of pediatric ACT are associated with p.R337H germline mutation, it is not a predictor of poor outcome in children and adolescents with ACT. On the other side, TP53 somatic mutations define a subgroup of adult ACC with different tumorigenesis and unfavorable prognosis. IGF system has a central role in the malignant phenotype of ACT, but in adult tumors it is mediated by IGF2 over-expression and in pediatric tumors by IGF1R over-expression. Finally, SF1 over-expression is associated with decreased overall survival and recurrence-free survival in adult ACC, but not in the pediatric group. In conclusion, discriminating benign and malignant behavior is more challenging in pediatric ACT than in adult tumors.
肾上腺皮质癌（ACC）是一种预后不良的罕见恶性肿瘤。在巴西南部，儿童肾上腺皮质肿瘤（ACT）的发病率极高，估计比世界发病率高 15 倍，这是由于 TP53 基因的种系突变（p.R337H）频率较高。与成人不同，根据组织病理学特征判断预后不良的儿童肾上腺皮质肿瘤往往具有良好的临床结局。高 Weiss 评分绝对不是儿童生存的良好预测指标，但它对成人肿瘤的不良预后更具区分性。除了预后方面的重要差异外，儿童和成人的肾上腺皮质肿瘤发生具有明显不同的模式。在这篇综述中，我们总结了我们和其他机构的最新数据，表明分子标志物的预后重要性在儿童和成人 ACT 之间有显著差异。尽管大多数儿童 ACT 与种系突变 p.R337H 相关，但它不是儿童和青少年 ACT 预后不良的预测指标。另一方面，TP53 体细胞突变定义了一组具有不同肿瘤发生和不良预后的成人 ACC。IGF 系统在 ACT 的恶性表型中起核心作用，但在成人肿瘤中由 IGF2 过表达介导，在儿童肿瘤中由 IGF1R 过表达介导。最后，SF1 过表达与成人 ACC 的总生存期和无复发生存期缩短相关，但与儿科组无关。总之，在儿童 ACT 中区分良性和恶性行为比在成人肿瘤中更具挑战性。
