Manual assessment of the level of expression of the tumor suppressor BRCA1-associated protein 1 (BAP1) in tumor cell nuclei can identify patients with a high risk of developing metastases, but may suffer from poor reproducibility.
Regarding time to clinically detected metastases, the first 2 peaks appear to be associated with BAP1-mutated tumors and the late peak to SF3B1-mutated tumors.
The association between BAP1 expression and overall survival was assessed using Cox proportion hazards models adjusting for Fuhrman grade, pathologic stage, and the presence of pathologic metastases for the overall cohort and stratified by race.
In univariate analyses, patients with germline BAP1 mutations exhibited larger tumor diameters (mean, 15.9 vs 12.3 mm; P = .004) and higher rates of ciliary body involvement (75.0% vs 21.6%, P = .002) and metastases (71.4% vs 18.0%, P = .003) compared with control subjects.
The primary tumor showed no abnormalities in chromosome 3, whereas metastases showed deletion of at least 3q12.1-q24 and the BAP1 gene was not mutated.
To determine whether BAP1 gene and protein expression associates with different prognostic parameters in uveal melanoma and whether BAP1 expression correctly identifies patients as being at risk for metastases, following enucleation of the primary tumour.
Patients with a BAP1 mutation and absent BAP1 expression had an almost eightfold higher chance of developing metastases compared with those without these changes (P=0.002).