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

• Type of Material: Article
• Authors: Eszter Szalai, Emory University; Jill Wells, Emory University; Laura Ward, Emory University; Hans Grossniklaus, Emory University
• Language: English
• Date: 2018-02-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017 American Academy of Ophthalmology
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.ophtha.2017.07.018
• Title of Journal or Parent Work: Ophthalmology (Section 12 EMBASE)
• ISSN: 0014-4169
• Volume: 125
• Issue: 2
• Start Page: 203
• End Page: 209
• Grant/Funding Information: This study was supported in part by: NIH R01CA176001, NEI P300630 and Research to Prevent Blindness, Inc.; The sponsor or funding organization had no role in the design or conduct of this research.
• Keywords: Life Sciences & Biomedicine; RISK; CHROMOSOME 3 STATUS; PROGNOSIS; MESOTHELIOMA; TUMOR-SUPPRESSOR; Science & Technology; SOMATIC MUTATIONS; BAP1 PROTEIN; IMMUNOHISTOCHEMISTRY; EIF1AX; EXPRESSION; Ophthalmology
• Research Categories: Biology, Biostatistics; Health Sciences, Pathology; Health Sciences, Immunology

Abstract

Purpose: 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 clinicopathologic features. Design: Retrospective case series. Participants: Forty patients with uveal melanoma (mean age, 57.98±14.75 years) were included in this analysis, of whom 20 had no metastatic disease and 20 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× (grades 0–3). Main Outcome Measures: Tumor size, histologic features, nuclear and cytoplasmic BAP1 immunoreactivity grade, and patient outcome, including development of metastasis. Results: Significantly lower (P = 0.025) nuclear 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). In addition, 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 patients with uveal melanoma with high nuclear BAP1 stain (P = 0.004). Conclusions: Time to metastasis differs in patients with primary uveal melanoma with different grades of nuclear BAP1 immunoreactivity. 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.