PRAME 染色在鼻腔鼻窦黏膜黑色素瘤中的应用：单中心经验。
PRAME Staining in Sinonasal Mucosal Melanoma: A Single-Center Experience.
机构信息
Department of Head and Neck Surgical Oncology, University Medical Center Utrecht, Utrecht, The Netherlands.
Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
出版信息
Head Neck Pathol. 2023 Jun;17(2):401-408. doi: 10.1007/s12105-022-01515-9. Epub 2022 Dec 31.
BACKGROUND
Sinonasal mucosal melanoma (MM) is a rare, aggressive melanoma subtype. Complete surgical excision, with or without adjuvant radiotherapy, remains the cornerstone of treatment and yields adequate locoregional control. Metastatic MM is managed similarly to metastatic cutaneous melanoma but with poorer survival. PReferentially expressed Antigen in MElanoma (PRAME) has been identified as a potential diagnostic marker and therapeutic target in the treatment of cutaneous melanoma.
METHODS
Retrospective analysis of the clinical characteristics and immunohistochemical features of all sinonasal MM patients referred to the department of Head and Neck Surgical Oncology, UMC Utrecht Cancer Center, between 2011 and 2021 was performed. Single nucleotide polymorphism (SNP) array and next-generation sequencing (NGS) were performed in selected cases.
RESULTS
A total of 26 patients with an MM were included. The median follow-up duration was 15 months. At the end of follow-up, 13 patients had died due to progression of their disease, and one patient died of intercurrent disease. PRAME immunohistochemistry was performed in 23 out of 26 cases, all displaying PRAME expression. In two cases PRAME expression was present both within the melanoma cells and in melanocytes in adjacent mucosa. SNP array showed ≥ 5 copy number variants (CNV) in all tested cases, with a median of 29.5 CNVs (IQR 23.25-40). The three most common mutations identified by NGS were NRAS (7 cases) and NF1 (2 cases).
CONCLUSION
We show that expression of PRAME is common in sinonasal MM, making PRAME a useful ancillary diagnostic tool and a potential therapeutic target in sinonasal MM. The demonstrated occurrence of extensive presence of PRAME-positive melanocytes in the surrounding mucosa of sinonasal MM might explain the multifocal nature of melanoma in the (sinonasal) mucosa, and would be an extra argument for a PRAME targeting treatment in preventing local disease recurrence.
背景
鼻腔鼻窦黑色素瘤（MM）是一种罕见的侵袭性黑色素瘤亚型。完整的手术切除，无论是否联合辅助放疗，仍然是治疗的基石，可获得充分的局部区域控制。转移性 MM 的治疗与转移性皮肤黑色素瘤相似，但预后较差。黑色素瘤优先表达抗原（PRAME）已被确定为治疗皮肤黑色素瘤的潜在诊断标志物和治疗靶点。
方法
对 2011 年至 2021 年间在乌得勒支大学医学中心头颈肿瘤外科就诊的所有鼻腔鼻窦 MM 患者的临床特征和免疫组织化学特征进行回顾性分析。在选定的病例中进行单核苷酸多态性（SNP）阵列和下一代测序（NGS）。
结果
共纳入 26 例 MM 患者。中位随访时间为 15 个月。随访结束时，13 例患者因疾病进展死亡，1 例患者因并发疾病死亡。26 例患者中有 23 例进行了 PRAME 免疫组织化学检测，均显示 PRAME 表达。在 2 例患者中，黑色素瘤细胞内和相邻黏膜内的黑素细胞均存在 PRAME 表达。SNP 阵列显示所有检测病例均存在≥5 个拷贝数变异（CNV），中位数为 29.5 CNV（IQR 23.25-40）。通过 NGS 鉴定的三个最常见突变是 NRAS（7 例）和 NF1（2 例）。
结论
我们表明 PRAME 在鼻腔鼻窦 MM 中表达常见，使其成为鼻腔鼻窦 MM 中有用的辅助诊断工具和潜在的治疗靶点。在鼻腔鼻窦 MM 周围黏膜中广泛存在 PRAME 阳性黑素细胞的现象，可能解释了（鼻腔）黏膜中黑色素瘤的多灶性特征，并且为 PRAME 靶向治疗预防局部疾病复发提供了额外的论据。
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