Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, USA.
Mod Pathol. 2019 Dec;32(12):1727-1733. doi: 10.1038/s41379-019-0335-4. Epub 2019 Aug 2.
Mucosal melanomas are rare, and less is known about the biomarkers of this subtype in comparison to cutaneous or uveal melanomas. Preferentially expressed antigen in melanoma (PRAME) has been studied as a tool for prognostication of uveal melanomas, and immunotherapy against PRAME-expressing tumor cells has already shown promise. Our goal was to retrospectively analyze 29 cases of mucosal melanomas at our institution to determine if any molecular and histopathologic prognosticators could be identified, as well as to study PRAME expression and its association with prognosis. We found that the majority of mucosal melanomas expressed PRAME and a high PRAME expression score predicted a poor prognosis. There was no association between prognosis and the histomorphologic features analyzed, such as presence of spindle cell or epithelioid predominance. BRAF mutations were absent in 16 of 16 cases tested. Pathogenic NRAS mutations were detected in 3 of 11 cases tested and were associated with shorter overall survival compared to those without NRAS alterations, but the presence of NRAS mutations did not correlate with PRAME expression. In conclusion, an increase in PRAME expression and the presence of a pathogenic NRAS were both associated with a worse prognosis in mucosal melanomas.
黏膜黑色素瘤较为罕见，与皮肤或葡萄膜黑色素瘤相比，人们对这种亚型的生物标志物了解较少。黑色素瘤优先表达抗原（PRAME）已被研究作为葡萄膜黑色素瘤预后的工具，针对表达 PRAME 的肿瘤细胞的免疫疗法已显示出前景。我们的目的是回顾性分析我们机构的 29 例黏膜黑色素瘤病例，以确定是否可以确定任何分子和组织病理学预后指标，以及研究 PRAME 表达及其与预后的关系。我们发现，大多数黏膜黑色素瘤表达 PRAME，高 PRAME 表达评分预示着预后不良。预后与分析的组织形态特征之间没有关联，例如存在梭形细胞或上皮样优势。在 16 例检测的病例中均未发现 BRAF 突变。在 11 例检测的病例中检测到致病性 NRAS 突变，与无 NRAS 改变的病例相比，总生存期更短，但 NRAS 突变的存在与 PRAME 表达无关。总之，PRAME 表达增加和致病性 NRAS 的存在均与黏膜黑色素瘤的预后不良相关。
