Characterization of PRAME immunohistochemistry reveals lower expression in pediatric melanoma compared to adult melanoma

IF 3.9 3区 医学 Q2 CELL BIOLOGY Pigment Cell & Melanoma Research Pub Date : 2024-03-20 DOI:10.1111/pcmr.13167
Stephan Forchhammer, Valentin Aebischer, Daniela Lenders, Christian M. Seitz, Christopher Schroeder, Alexandra Liebmann, Michael Abele, Hannah Wild, Ewa Bien, Malgorzata Krawczyk, Dominik T. Schneider, Ines B. Brecht, Lukas Flatz, Matthias Hahn
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Abstract

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.

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PRAME 免疫组化的特征显示,与成人黑色素瘤相比,小儿黑色素瘤中的 PRAME 表达较低。
小儿黑色素瘤是一种罕见的肿瘤,在临床和组织学上与成人黑色素瘤有所不同。在成人黑色素瘤中,免疫组化标记物 PRAME 越来越多地被用作辅助诊断手段。PRAME 还被研究用作下一代免疫疗法(包括 T 细胞诱导剂)的靶结构。人们对小儿黑色素瘤中 PRAME 的表达特点知之甚少。在这项回顾性研究中,我们将 25 例小儿黑色素瘤样本与对照组的年轻成人黑色素瘤(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 PRAME 免疫组化表达(弥漫 PRAME 表达 >75%/绝对表达)进行了比较。与年轻成人黑色素瘤(15.6%/46.8%)和成人黑色素瘤(50%/70%)相比,小儿黑色素瘤的PRAME弥漫表达较低(4%),PRAME绝对表达较低(25%)。可以观察到明显的年龄依赖性表达。对无事件生存期的分析表明,PRAME在小儿黑色素瘤和年轻成人黑色素瘤中没有预后作用,但在成年黑色素瘤中与PRAME的弥漫表达有显著关联。PRAME 表达的年龄依赖性给年轻患者黑色素细胞肿瘤的诊断应用带来了潜在的隐患,并可能限制该年龄组患者的治疗选择。肿瘤相关抗原 PRAME 的免疫组化表达是一种日益重要的黑色素细胞肿瘤诊断标志物,并作为黑色素瘤的一种可能免疫治疗靶点而受到越来越多的关注。由于现有数据主要来源于成人黑色素瘤,而儿科黑色素瘤在临床和组织学上存在差异,因此我们对PRAME在这一特殊患者群体中表达情况的了解仍然有限。本文所显示的与年龄相关的低PRAME表达限制了这一标记物在小儿黑色素瘤中的应用,也可能限制了针对PRAME的免疫治疗策略在年轻患者中的应用。
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来源期刊
Pigment Cell & Melanoma Research
Pigment Cell & Melanoma Research 医学-皮肤病学
CiteScore
8.90
自引率
2.30%
发文量
54
审稿时长
6-12 weeks
期刊介绍: Pigment Cell & Melanoma Researchpublishes manuscripts on all aspects of pigment cells including development, cell and molecular biology, genetics, diseases of pigment cells including melanoma. Papers that provide insights into the causes and progression of melanoma including the process of metastasis and invasion, proliferation, senescence, apoptosis or gene regulation are especially welcome, as are papers that use the melanocyte system to answer questions of general biological relevance. Papers that are purely descriptive or make only minor advances to our knowledge of pigment cells or melanoma in particular are not suitable for this journal. Keywords Pigment Cell & Melanoma Research, cell biology, melatonin, biochemistry, chemistry, comparative biology, dermatology, developmental biology, genetics, hormones, intracellular signalling, melanoma, molecular biology, ocular and extracutaneous melanin, pharmacology, photobiology, physics, pigmentary disorders
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