Prognostic value of BAP1 expression in uveal melanoma: a comparative study with histopathological factors in a large Spanish cohort.

To evaluate the prognostic significance of BRCA1-associated protein 1 (BAP1) nuclear expression in enucleated eyes with uveal melanoma (UM), and to compare its predictive value with classical clinicopathological factors in a large Spanish cohort. Prospective, single-center, observational-cohort study. A total of 150 consecutive patients diagnosed with posterior uveal melanoma and treated with primary enucleation at a national reference center between 2006 and 2024. Immunohistochemical analysis of BAP1 expression was performed on formalin-fixed, paraffin-embedded tumor sections. Nuclear staining was classified as low grade (<33% positive tumor nuclei) or high grade (≥33%). Clinicopathological features and survival outcomes were assessed, and multivariate Cox regression was used to identify independent prognostic factors for melanoma-specific survival. Melanoma-specific survival and its association with BAP1 nuclear expression and classical prognostic variables. Low grade nuclear BAP1 expression was detected in 50% of tumors and was significantly associated with worse melanoma-specific survival (hazard ratio [HR] = 2.72; 95% confidence interval [CI]: 1.04-7.11; p = 0.041). Additional independent predictors of poor prognosis included vortex vein invasion (HR = 4.55; p = 0.028), extrascleral extension (HR = 4.73; p = 0.004), and epithelioid cell type (HR = 4.12; p = 0.019). No significant association was observed between BAP1 expression and sex, mitotic index, or Ki-67 proliferation rate. Low grade nuclear BAP1 immunostaining is a strong, independent predictor of poor prognosis in uveal melanoma, comparable to established histopathological features. Immunohistochemical assessment of BAP1 is a cost-effective tool for risk stratification in routine clinical practice.