Uveal melanoma is the most common primary malignant tumor of the eye. It is characterized by a low mutational burden and a limited response to immunotherapy, which is largely attributable to the immune-privileged status of the eye. Decreased expression of the BAP1 protein and specific features of the tumor microenvironment may influence disease prognosis, but its prognostic significance remains insufficiently investigated.

PURPOSE

This study aimed to assess the impact of tumor microenvironment characteristics and BAP1 expression levels on survival in patients with uveal melanoma.

MATERIAL AND METHODS

Retrospective analysis included 58 patients (58 eyes) with stage IIIA—IIIC uveal melanoma who underwent eye enucleation between 2014 and 2023 at the Moscow Regional Research and Clinical Institute (MONIKI). All specimens were subjected to morphological examination and immunohistochemical analysis using antibodies against BAP1, CD4, CD8, CD20, and CD68. Survival was evaluated using the Kaplan—Meier method, and the influence of prognostic factors was assessed using the Cox proportional hazards model.

RESULTS

Uniform or heterogeneous loss of BAP1 expression was detected in 55.2% of tumors and was associated with poorer survival compared with tumors retaining BAP1 expression (p=0.009). Presence of at least one immune marker (CD4⁺, CD8⁺, or CD68⁺) also correlated with worse prognosis (p=0.036). The most unfavorable outcomes were observed in cases combining BAP1 loss with the presence of these immune cells (p=0.01; HR=4.49; 95% CI: 1.63—12.37). No deaths were recorded in the subgroup of patients with preserved BAP1 expression and absence of CD4⁺, CD8⁺, and CD68⁺ cells.

CONCLUSION

Loss of BAP1 expression in combination with immune cell infiltration in the tumor microenvironment is associated with an increased risk of mortality in uveal melanoma. Combined assessment of BAP1 and immune markers enables more accurate patient stratification and refinement of prognostic evaluation.