Clinicopathological Characteristics and BAP1 Expression in an Enucleation-Based Uveal Melanoma Cohort: A...

Loss of nuclear BAP1 (BRCA1-associated protein 1) expression is a well-established adverse prognostic marker in uveal melanoma (UM). However, data from Central and Southeastern European populations are limited. This descriptive study aimed to evaluate BAP1 immunohistochemical expression in a Croatian enucleation-based UM cohort, characterize its associations with clinicopathological parameters, and contextualize the findings within the published literature.

Formalin-fixed, paraffin-embedded tumor tissue from 58 consecutive patients with primary choroidal and ciliary body melanoma treated with enucleation at University Hospital Centre Zagreb (2006-2016) was analyzed immunohistochemically for BAP1 nuclear expression. Associations with clinicopathological parameters were assessed using chi-square and Fisher's exact tests. Survival analysis was performed using Kaplan-Meier estimation, log-rank tests, and Cox proportional hazards regression with a median follow-up of 11.2 years.

Loss of nuclear BAP1 expression was observed in 53/58 (91.4%) specimens, resulting in a severely imbalanced distribution (53 versus 5 patients) precluding meaningful comparative survival analysis. Five-year and 10-year overall survival rates were 72.4% and 51.7%, respectively, with a median overall survival of 14.5 years. BAP1 loss was associated with longer disease-free survival (log-rank p = 0.020); however, this finding likely reflects a statistical artifact attributable to the extremely small BAP1-retained group (n = 5) harboring concurrent adverse features and should not be interpreted biologically. The study was underpowered to draw prognostic inferences regarding BAP1 status. Exploratory survival analyses are presented for transparency but should not be interpreted inferentially.

The exceptionally high prevalence of BAP1 loss reflects the selection bias inherent in enucleation-based cohorts, which are enriched for large, molecularly high-risk tumors. This study provides the first comprehensive BAP1 immunohistochemical data from Croatia, contributing to the growing evidence that enucleation cohorts represent a distinct, biologically high-risk subgroup in which BAP1 immunohistochemistry offers limited discriminatory value. The extended follow-up of 11.2 years confirms the prolonged natural history of UM. Future multi-center studies incorporating molecular validation and diverse treatment modalities are needed to establish the prognostic utility of BAP1 across the full spectrum of UM disease.