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Eszter Szalai, Jill R. Wells, Hans E Grossniklaus; Correlation of BAP1 immunoreactivity with metastasis in uveal melanoma. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2503. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To examine the BRCA1-associated protein-1 (BAP1) expression of primary uveal melanomas without and with metastasis, and to analyze the correlation between the BAP1 immunoreactivity and clinico-pathologic features of the tumor.
Medical records and histology slides of patients with primary uveal melanoma treated by enucleation were reviewed. BAP1 expression was evaluated immunohistochemically on formalin-fixed paraffin-embedded sections, and immunoreactivity in the nucleus and cytoplasm was graded by estimating the percentage of tumor cells showing a positive stain per high power field (grade 0 to 4).
Forty uveal melanoma patients (mean age: 57.98±14.75 years) were included in this analysis, of which twenty patients had no metastatic disease and 20 patients had metastasis. The median nuclear BAP1 grade was 2, the median cytoplasmic BAP1 grade was 3. Significantly lower nuclear (P=0.006) and cytoplasmic (P=0.009) BAP1 immunoreactivity was observed in the metastatic melanoma group. Patients with grade 3-4 nuclear and grade 4 cytoplasmic BAP1 stain had significantly longer metastasis-free survival than patients with low nuclear (P<0.0001) and cytoplasmic (P=0.019) BAP1 expression (Figure 1). Greater tumor thickness, basal diameter, more advanced TNM stage and higher GEP class were associated with increased odds of developing metastasis (P<0.05). Additionally, higher grade nuclear (P=0.004) and cytoplasmic (P=0.006) BAP1 expression were associated with decreased odds of developing metastatic disease.
We conclude that there is a difference in time to metastasis in uveal melanoma patients with different grades of nuclear and cytoplasmic BAP1 immunoreactivity. Patients with low nuclear and cytoplasmic BAP1 staining showed an increased risk of metastasis. Our data support the assumption that both high nuclear and cytoplasmic BAP1 expressions are associated with decreased metastasis in patients with uveal melanoma.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
Figure 1. Kaplan-Meier metastasis-free survival curves for uveal melanoma patients stratified by the median nuclear (A) and cytoplasmic (B) BAP1 score.
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