Abstract
INTRODUCTION: Loss of BAP1 protein expression emerged as a negative prognostic marker in uveal melanoma (UM) and has primarily been studied in enucleations. Intraocular biopsy is frequently performed prior to UM globe-conserving therapy. METHODS: We retrospectively evaluated BAP1 immunostaining of UM in 16 biopsies and 8 subsequent enucleations, and results were correlated with the UM-specific gene expression profile (GEP; n = 11), chromosome 3 status by FISH and/or chromosomal microarray (n = 12; 9 also had GEP), and clinical outcomes. RESULTS: UM involved the choroid in 15 (of 16) cases. Biopsy was performed for prognostication (n = 12) or diagnosis (n = 4). Treatment included brachytherapy (n = 13; 5 followed by enucleation) or enucleation only (n = 3). BAP1 nuclear immunostaining was positive in 9, negative in 4, and equivocal in 3 biopsies. For the 3 equivocal biopsies, BAP1 immunostaining was positive in 2 (of 3) subsequent enucleations. BAP1 immunostaining was concordant between all 5 remaining biopsies and enucleations. BAP1-positive biopsies had disomy 3 (n = 6) or 3p loss (n = 1) and class 1 GEP (n = 6). BAP1-negative biopsies had monosomy 3 (n = 3) and class 2 GEP (n = 2). Median follow-up was 62.5 months (range, 17-150). For BAP1-positive UM patients, 8 were alive (7 without metastatic disease) and 3 had died (1 melanoma-related death). Among BAP1-negative UM patients, 2 were alive (1 with metastatic disease) and 3 had melanoma-related deaths. CONCLUSION: BAP1 immunostaining in biopsies highly correlates with results in subsequent enucleations and with well-established UM prognostic markers, representing a potential additional prognostic tool for UM biopsies.