Cytopathology and Prognostic Accuracy of 15-GEP/PRAME

IF 10.5 1区医学 Q1 OPHTHALMOLOGY

JAMA ophthalmology Pub Date : 2026-10-15 DOI:10.1001/jamaophthalmol.2026.4378

Anne Marie Lane, Amy C. Schefler, Zelia M. Correa, Miguel A. Materin, Alison H. Skalet, Kisha D. Piggott, Thomas M. Aaberg, Basil K. Williams, Prithvi Mruthyunjaya, Scott C. N. Oliver, Devron Char, Scott D. Walter, Antonio Capone, Shilpa Desai, Tony Tsai, Dan S. Gombos, Jill R. Wells, Hakan Demirci, Michael Cusick, Timothy Fuller, Peter Hovland, Cameron Javid, Michael M. Altaweel, Ezekiel Weis, David A. Reichstein, John Mason, J. William Harbour, Ivana K. Kim

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引用次数: 0

Abstract

Importance Gene expression profiling (GEP) reliably predicts metastatic uveal melanoma risk and is used to manage uveal melanoma (UM) in patients with this diagnosis. Efforts to refine molecular prognostication continue. Objective To determine if confirmatory cytopathology findings influence the prognostic accuracy of a commercially available GEP/Preferentially Expressed Antigen in Melanoma (PRAME) assay. Design, Setting, and Participants The Collaborative Ocular Oncology Group 2 study, a prospective cohort study, was conducted from 2017 to 2020 with follow-up recorded at 6-month intervals. This was a multicenter study that included patients with choroidal and/or ciliary body melanoma and results from a 15-GEP and PRAME RNA expression (15-GEP/PRAME) assay. Patients with iris tumors or less than 6 months’ follow-up were excluded. Study data were analyzed from April 2025 to July 2026. Exposures 15-GEP/PRAME, cytopathology, and next-generation sequencing (NGS). Main Outcomes and Measures Metastatic uveal melanoma rates in patients who had 15-GEP/PRAME and confirmatory cytopathology (CCP) results confirming or suspicious for UM (GEP+CCP) were compared with those who had 15-GEP/PRAME and no cytopathology performed, or unknown or nondiagnostic cytopathology results (GEP only). UM-associated variants identified by NGS were also evaluated. Results Of 1537 patients (mean [SD] age, 62.0 [13.4] years; 787 male [51.2%]), 727 (47.3%) had CCP results, and 810 (52.7%) had nondiagnostic cytopathology results or no cytopathology performed. Class 2/PRAME+ tumors were more common (136 of 727 [18.7%]) in the GEP+CCP group than in the GEP-only group (72 of 810 [8.9%]; 9.8% difference; 95% CI, 6.4-13.3; P &lt;.001), whereas class 1/PRAME– tumors were less common (330 of 727 [45.4%] vs 495 of 810 [61.1%]; 15.7% difference; 95% CI, 10.8-20.6; P &lt;.001). In patients with GEP+CCP, 22.7% (n = 165) developed metastasis vs 15.4% (n = 125) in patients with GEP only (7.3% difference, 95% CI, 3.3-11.2; P &lt; .001). Adjusting for 15-GEP/PRAME status, there were no differences in metastasis rates between CCP groups. Of 1327 patients with successful NGS, 94.1% (605 of 643) in the GEP+CCP group and 71.9% (492 of 684) in the GEP-only group had a UM-associated variant (22.2% difference, 95% CI, 18.3-26.0; P &lt; .001). Conclusions and Relevance Results of this cohort study reveal that no differences in metastasis outcomes were observed between patients with and without CCP within any GEP/PRAME categories. UM-associated variants were found less frequently in the GEP-only group than in the GEP+CCP group. In this cohort, 15-GEP/PRAME classification without CCP retained prognostic validity, supporting its clinical consideration in guiding metastatic surveillance in cases in which cytopathology is unavailable.

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15-GEP/PRAME的细胞病理学和预后准确性

基因表达谱（GEP）可靠地预测转移性葡萄膜黑色素瘤的风险，并用于治疗这种诊断的葡萄膜黑色素瘤（UM）患者。改进分子预测的努力仍在继续。目的确定确证性细胞病理学结果是否影响市售的黑色素瘤优先表达抗原（PRAME）检测的预后准确性。眼肿瘤学第二组合作研究是一项前瞻性队列研究，于2017年至2020年进行，每6个月随访一次。这是一项多中心研究，纳入了脉络膜和/或纤毛体黑色素瘤患者，结果来自15-GEP和PRAME RNA表达（15-GEP/PRAME）测定。排除有虹膜肿瘤或随访时间小于6个月的患者。研究数据分析时间为2025年4月至2026年7月。暴露15-GEP/PRAME，细胞病理学和下一代测序（NGS）。将15-GEP/PRAME和确认性细胞病理学（CCP）结果证实或怀疑UM （GEP+CCP）的患者的转移性葡萄膜黑色素瘤发生率与15-GEP/PRAME和未进行细胞病理学检查，或未知或非诊断性细胞病理学结果（仅GEP）的患者进行比较。通过NGS鉴定的um相关变异也进行了评估。结果1537例患者（平均[SD]年龄62.0[13.4]岁，男性787例[51.2%]），727例（47.3%）有CCP结果，810例（52.7%）有非诊断性细胞病理学结果或未行细胞病理学检查。2类/PRAME+肿瘤在GEP+CCP组（727例中有136例[18.7%]）比仅GEP组（810例中有72例[8.9%]）更常见，差异为9.8%;95% CI, 6.4-13.3; P &lt；1类/PRAME -肿瘤较少见（727例中有330例[45.4%]vs 810例中有495例[61.1%]；差异为15.7%;95% CI, 10.8-20.6; P & lt;.001）。在GEP+CCP患者中，22.7% （n = 165）发生转移，而仅GEP患者为15.4% (n = 125)（差异为7.3%,95% CI, 3.3-11.2; P & lt; .001）。调整15-GEP/PRAME状态后，CCP组间转移率无差异。在1327例成功的NGS患者中，94.1%（643例中有605例）的GEP+CCP组和71.9%（684例中有492例）的GEP组存在um相关变异（差异为22.2%,95% CI, 18.3-26.0; P & lt; 0.001）。本队列研究的结果显示，在任何GEP/PRAME类别中，CCP患者和非CCP患者的转移结局均无差异。与GEP+CCP组相比，仅GEP组发现um相关变异的频率较低。在该队列中，没有CCP的15-GEP/PRAME分类保留了预后有效性，支持其在无法获得细胞病理学检查的病例中指导转移监测的临床考虑。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

JAMA ophthalmology OPHTHALMOLOGY-

CiteScore

13.20

自引率

3.70%

发文量

340

期刊介绍： JAMA Ophthalmology, with a rich history of continuous publication since 1869, stands as a distinguished international, peer-reviewed journal dedicated to ophthalmology and visual science. In 2019, the journal proudly commemorated 150 years of uninterrupted service to the field. As a member of the esteemed JAMA Network, a consortium renowned for its peer-reviewed general medical and specialty publications, JAMA Ophthalmology upholds the highest standards of excellence in disseminating cutting-edge research and insights. Join us in celebrating our legacy and advancing the frontiers of ophthalmology and visual science.