Uveal Melanoma Nuclear BRCA1-Associated Protein-1 Immunoreactivity Is an Indicator of Metastasis

Abstract

Objective: 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 of primary uveal melanoma and other clinico-pathologic features. Design: Retrospective case series. Subjects: 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. Methods: Medical records and histology slides of patients with primary uveal melanoma treated by enucleation were reviewed. BAP1 expression was evaluated by immunohistochemical staining of formalin fixed paraffin embedded sections. Immunoreactivity in the nucleus and cytoplasm were graded by estimating the percentage of primary tumor cells showing a positive staining of their nucleus or cytoplasm per 1 high power field 200× (grade 0 to 3). Main outcome measures: Tumor size, histologic features, nuclear and cytoplasmic BAP1 immunoreactivity grade and patient outcome including development of metastasis. Results: Significantly lower nuclear (P=0.025) BAP1 immunoreactivity was observed in the metastatic melanoma group. Greater tumor thickness, basal diameter and more advanced TNM stage were associated with an increased odds ratio of developing metastasis (P<0.05). Additionally, tumors with a higher proportion of cells expressing nuclear BAP1 had decreased odds of developing metastatic disease in a multivariate model (P=0.042). Metastasis-free survival was significantly longer in uveal melanoma patients with high nuclear BAP1 stain (P=0.004). Conclusions: There is a difference in time to metastasis in uveal melanoma patients with different grades of nuclear BAP1 immunoreactivity measured in primary uveal melanoma. Nuclear BAP1 stain is the only significant independent predictor of metastatic disease in this study. Our data support the role of BAP1 immunohistochemical staining of primary uveal melanoma to evaluate metastatic risk.

Spontaneous Necrosis of a Large Choroidal Melanoma: Unusual Presentation in a 49-Year-Old Male

“…Whilst it could be hypothesised that, in the current case, an aggressive clone (possibly monosomy 3 and nuclear BAP1 negative) of choroidal melanoma cells may have proliferated more rapidly, pushing through and causing the extensive necrosis and ocular damage, our experience is that most choroidal melanomas do not display notable heterogeneity, neither for chromosomal aberrations nor for BAP1 immunohistochemistry [18,19]. These findings have been supported by others [20][21][22]. Ocul Oncol Pathol 2020;6:174-179 DOI: 10.1159/000501522 New single sequencing techniques may provide further data to understand choroidal melanoma progression in the future.…”

The Potential Role of Selected miRNA in Uveal Melanoma Primary Tumors as Early Biomarkers of Disease Progression

“…It is known that chromosome 3 monosomy and the loss of BAP1 expression are related to poor prognosis and an increased risk of developing metastatic disease in uveal melanoma [5,45,46]. Chromosome 3 and BAP1 status were also determined in our validation cohort of patients and associated with progression-free survival.…”

Prognostic value of chromosomal imbalances, gene mutations, and BAP1 expression in uveal melanoma

“…Previous studies showed that the consequence of out‐of‐frame mutations is the absence of BAP1 nuclear protein, with some exceptions . In our UM series, univariate analysis showed that chromosome 3 monosomy, 8q gain, BAP1 mutations, and loss of BAP1 nuclear immunostaining were all significantly associated with metastatic progression, in agreement with previous studies …”