Fortes Precious Ann, Nguyen Michelle, Fung Po Chu, Rodriguez Erika F, Kim Teresa H, Kawai Kosuke, Moatamed Neda A
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Department of Medicine Statistics Core, David Geffen School of Medicine at the University of California, Los Angeles, California, USA.
Diagn Cytopathol. 2025 Jun 17. doi: 10.1002/dc.25496.
Loss of nuclear BRCA1-associated protein 1 (nBAP1) expression is strongly linked to monosomy 3 in uveal melanoma. While fine-needle aspiration (FNA) aids diagnosis, the prognostic value of nBAP1 immunocytochemistry (ICC) is still being investigated. This study examines the correlation between nBAP1 loss on ICC and fluorescence in situ hybridization (FISH) findings, as well as its clinical impact.
Intraocular FNA cytology specimens with clinical concern for uveal melanoma from April 2015 to March 2023 with available nBAP1 ICC, FISH results, and clinical follow-up were examined. Two independent reviewers, blinded to the cytogenetic results, interpreted the nBAP1 ICC as either loss or retained. Statistical analysis using Fisher's exact test was utilized to evaluate the relationship between nBAP1 loss on ICC and FISH findings. Kaplan-Meier survival plots were constructed to examine the metastasis-free survival.
Among the 79 cases included in the study, 86.1% (68/79) showed nBAP1 loss. Approximately 63.2% of patients with nBAP1 loss had monosomy 3, whereas none with nBAP1 retained had monosomy 3 (p < 0.001). Of the nBAP1 loss cases, 41.2% (28/68) had monosomy 3 alone, while 22.1% (15/68) had both monosomy 3 and 6p gain. Patients with nBAP1 loss had a significantly higher risk of metastasis (p ≤ 0.04), with a 5-year metastasis-free survival of 57.1% versus 100% in nBAP1 retained cases.
BAP1 ICC is a cost-effective prognostic tool in uveal melanoma FNAs, strongly correlating with monosomy 3 and poor outcomes. Integrating BAP1 ICC with FISH enhances risk stratification, enabling earlier identification of high-risk patients and guiding treatment decisions.
核BRCA1相关蛋白1（nBAP1）表达缺失与葡萄膜黑色素瘤中的3号染色体单体密切相关。虽然细针穿刺抽吸（FNA）有助于诊断，但nBAP1免疫细胞化学（ICC）的预后价值仍在研究中。本研究探讨了ICC检测到的nBAP1缺失与荧光原位杂交（FISH）结果之间的相关性及其临床影响。
对2015年4月至2023年3月间有葡萄膜黑色素瘤临床疑虑且有可用nBAP1 ICC、FISH结果及临床随访资料的眼内FNA细胞学标本进行检查。两名独立的审阅者在不知晓细胞遗传学结果的情况下，将nBAP1 ICC解释为缺失或保留。采用Fisher精确检验进行统计分析，以评估ICC检测到的nBAP1缺失与FISH结果之间的关系。构建Kaplan-Meier生存曲线以检查无转移生存期。
在纳入研究的79例病例中，86.1%（68/79）显示nBAP1缺失。约63.2%的nBAP1缺失患者存在3号染色体单体，而nBAP1保留的患者均无3号染色体单体（p < 0.001）。在nBAP1缺失病例中，41.2%（28/68）仅存在3号染色体单体，而22.1%（15/68）同时存在3号染色体单体和6p增益。nBAP1缺失的患者转移风险显著更高（p≤0.04），5年无转移生存率为57.1%，而nBAP1保留的病例为100%。
BAP1 ICC是葡萄膜黑色素瘤FNA中一种具有成本效益的预后工具，与3号染色体单体及不良预后密切相关。将BAP1 ICC与FISH相结合可增强风险分层，有助于更早识别高危患者并指导治疗决策。
