Background: 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.
Methods: 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.
Results: 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.
Conclusion: 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.
Keywords: BAP1 nuclear loss; fine‐needle aspiration cytology; gain of 6p; monosomy 3; uveal melanoma.
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