Marques-Pereira Rosana, Delacerda Luiz, Lacerda Hadriano M, Michalkiewicz Edson, Sandrini Fabiano, Sandrini Romolo
Pediatric Endocrinology Unit, Department of Pediatrics, Clinical Hospital, Federal University of Parana; Curitiba PR, Brazil.
Hered Cancer Clin Pract. 2006 May 15;4(2):81-9. doi: 10.1186/1897-4287-4-2-81.
Childhood adrenocortical tumour (ACT) is not a common disease, but in southern Brazil the prevalence is 15 times higher than in other parts of the world. One hundred and thirty-seven patients have been identified and followed by our group over the past four decades. Affected children are predominantly girls, with a female-to-male ratio of 3.5:1 in patients below 4 years of age. Virilization alone (51.6%) or mixed with Cushing's syndrome (42.0%) was the predominant clinical picture observed in these patients. Tumours are unilateral, affecting both glands equally. TP53 R337H germline mutations underlie most childhood ACTs in southern Brazil. Epidemiological data from our casuistic studies revealed that this mutation has ~10% penetrance for ACT. Surgery is the definitive treatment, and a complete resection should always be attempted. Although adjuvant chemotherapy has shown some encouraging results, its influence on overall outcome is small. The survival rate is directly correlated to tumour size; patients with small, completely excised tumours have survival rates close to 90%, whereas in those patients with inoperable tumours and/or metastatic disease it is less than 10%. In the group of patients with large, excisable tumours, half of them have an intermediate outcome. Recent molecular biology techniques and genomic approaches may help us to better understand the pathogenesis of ACT, the risk of developing a tumour when TP53 R337H is present, and to predict its outcome. An ongoing pilot study consisting of close monitoring of healthy carriers of the TP53 R337H mutation - siblings and first-degree relatives of known affected cases - aims at the early detection of ACTs and an improvement of the cure rate.
儿童肾上腺皮质肿瘤（ACT）并非常见疾病，但在巴西南部，其患病率比世界其他地区高15倍。在过去四十年中，我们的团队已识别并跟踪了137例患者。受影响的儿童以女孩为主，4岁以下患者的男女比例为3.5:1。这些患者中主要的临床表现为单纯男性化（51.6%）或与库欣综合征混合（42.0%）。肿瘤为单侧性，双侧肾上腺受影响的几率相同。TP53 R337H种系突变是巴西南部大多数儿童ACT的病因。我们病例研究的流行病学数据显示，这种突变导致ACT的外显率约为10%。手术是确定性治疗方法，应始终尝试进行完整切除。尽管辅助化疗已显示出一些令人鼓舞的结果，但其对总体预后的影响较小。生存率与肿瘤大小直接相关；肿瘤小且完全切除的患者生存率接近90%，而对于无法手术的肿瘤和/或转移性疾病患者，生存率则低于10%。在可切除的大肿瘤患者组中，一半患者的预后处于中等水平。最近的分子生物学技术和基因组方法可能有助于我们更好地理解ACT的发病机制、存在TP53 R337H时发生肿瘤的风险以及预测其预后。一项正在进行的试点研究，包括对TP53 R337H突变的健康携带者——已知受影响病例的兄弟姐妹和一级亲属——进行密切监测，旨在早期发现ACT并提高治愈率。
