Nuclear expression of BAP-1 in transvitreal incisional biopsies and subsequent enucleation of eyes with posterior choroidal melanoma

BACKGROUND: As a majority of patients with choroidal melanoma do not undergo enucleation, tumour tissue for prognostic testing has to be obtained with alternate methods. Transvitreal incisional biopsies enable histological examination as well as immunohistochemical staining of BRCA1-associated protein-1 (BAP-1). METHODS: Fifty-nine patients diagnosed with choroidal melanoma in transvitreal biopsies between years 2003 and 2019 were included. Twenty-one of these patients subsequently underwent enucleation. The level of nuclear expression of BAP-1 in transvitreal biopsies and enucleations was evaluated and the concordance calculated. Metastasis-free survival and HR for metastasis were analysed. RESULTS: The mean tumour thickness and diameter at biopsy was 3.8 mm (SD 2.1) and 9.3 mm (SD 4.8), respectively. For biopsies, 37 of 59 tumours (63%) were classified as having high nuclear BAP-1 expression, and 22 (37%) as low. For enucleations, 13 of 21 tumours (62%) were classified as having high nuclear BAP-1 expression, and 8 (38%) as low. Eighty-six per cent of biopsies had an identical BAP-1 classification as the subsequent enucleation, yielding a Cohen’s kappa coefficient of 0.70. Patients with low nuclear BAP-1 expression in transvitreal biopsies had a significantly shorter metastasis-free survival (p=0.001), with a size-adjusted Cox regression HR for metastasis of 13.0 (95% CI 3.1 to 54.4, p=0.0004). CONCLUSION: Loss of nuclear BAP-1 expression occurred in a large proportion of the small tumours included in this study. BAP-1 immunoreactivity in transvitreal incisional biopsies of choroidal melanoma is substantially concordant with immunoreactivity in enucleated specimens and identifies patients with poor metastasis-free survival.