Department of Dermatology, Eberhard Karls University of Tübingen, Tübingen, Germany.
Pediatric Hematology and Oncology, Children's Hospital, Eberhard Karls University of Tübingen, Tübingen, Germany.
Pigment Cell Melanoma Res. 2024 Jul;37(4):453-461. doi: 10.1111/pcmr.13167. Epub 2024 Mar 20.
Pediatric melanomas are rare tumors that have clinical and histological differences from adult melanomas. In adult melanoma, the immunohistochemical marker PRAME is increasingly employed as a diagnostic adjunct. PRAME is also under investigation as a target structure for next-generation immunotherapies including T-cell engagers. Little is known about the characteristics of PRAME expression in pediatric melanoma. In this retrospective study, samples from 25 pediatric melanomas were compared with control groups of melanomas in young adults (18-30 years; n = 32), adult melanoma (>30 years, n = 30), and benign melanocytic nevi in children (0-18 years; n = 30) with regard to the immunohistochemical expression of PRAME (diffuse PRAME expression >75%/absolute expression). Pediatric melanomas show lower diffuse PRAME expression (4%) and lower absolute PRAME expression (25%) compared to young adult melanomas (15.6%/46.8%) and adult melanomas (50%/70%). A significant age-dependent expression could be observed. An analysis of event-free survival shows no prognostic role for PRAME in pediatric melanoma and young adult melanoma, but a significant association with diffuse PRAME expression in adulthood. The age dependency of PRAME expression poses a potential pitfall in the diagnostic application of melanocytic tumors in young patients and may limit therapeutic options within this age group. The immunohistochemical expression of the tumor-associated antigen PRAME is an increasingly important diagnostic marker for melanocytic tumors and is gaining attention as a possible immunotherapeutic target in melanoma. As the available data primarily stem from adult melanoma, and given the clinical and histological distinctions in pediatric melanomas, our understanding of PRAME expression in this specific patient group remains limited. The age-dependent low PRAME expression shown here constrains the use of this marker in pediatric melanoma and may also limit the use of immunotherapeutic strategies against PRAME in young patients.
儿科黑色素瘤是一种罕见的肿瘤，与成人黑色素瘤在临床和组织学上存在差异。在成人黑色素瘤中，免疫组织化学标志物 PRAME 越来越多地被用作辅助诊断。PRAME 也正在被研究作为下一代免疫疗法的靶结构，包括 T 细胞衔接物。关于儿科黑色素瘤中 PRAME 表达的特征，人们知之甚少。在这项回顾性研究中，将 25 例儿科黑色素瘤样本与年轻成人（18-30 岁；n=32）、成人黑色素瘤（>30 岁，n=30）和儿童良性黑素细胞痣（0-18 岁；n=30）的黑色素瘤对照组进行比较，比较内容为 PRAME 的免疫组织化学表达（弥漫性 PRAME 表达>75%/绝对表达）。与年轻成人黑色素瘤（15.6%/46.8%）和成人黑色素瘤（50%/70%）相比，儿科黑色素瘤的弥漫性 PRAME 表达（4%）和绝对 PRAME 表达（25%）较低。可以观察到明显的年龄依赖性表达。无事件生存分析显示，PRAME 在儿科黑色素瘤和年轻成人黑色素瘤中无预后作用，但在成年期与弥漫性 PRAME 表达呈显著相关。PRAME 表达的年龄依赖性在年轻患者中黑素细胞肿瘤的诊断应用中可能存在潜在的陷阱，并可能限制该年龄段的治疗选择。肿瘤相关抗原 PRAME 的免疫组织化学表达是黑素细胞肿瘤日益重要的诊断标志物，作为黑色素瘤的一种可能的免疫治疗靶点，越来越受到关注。鉴于现有数据主要来自成人黑色素瘤，且鉴于儿科黑色素瘤在临床和组织学上的差异，我们对该特定患者群体中 PRAME 表达的理解仍然有限。这里显示的年龄依赖性低 PRAME 表达限制了该标志物在儿科黑色素瘤中的应用，也可能限制了针对年轻患者的 PRAME 免疫治疗策略的应用。
