BAP1 Immunoreactivity Correlates with Gene Expression Class in Uveal Melanoma

Abstract

Background: Uveal melanoma (UM) is the most common intraocular tumour in adults. Currently there are different tests available to determine the risk of UM for metastasis, among which include BRCA1-associated protein-1 (BAP1) immunohistochemistry (IHC) and gene expression profiling (GEP). BAP1 is a deubiquitylating enzyme (DUB) that has tumour suppressor activity, the loss of which therefore is associated with higher risk for tumour growth and metastasis. Objectives: To compare and correlate the prognostic significance of BAP1-IHC staining patterns and GEP in the prediction of UM's risk for metastasis. Methods: This is a retrospective chart review with prospective follow-up of patients with primary UM who underwent enucleation from the year 2008 to 2018. Clinical history, histopathologic findings, GEP classification, BAP1-IHC of the formalin-fixed paraffin-embedded tissues, and follow-up data for metastasis were collected and statistically analysed. Results: A total of 30 enucleated eyes with UM were included in the study. All class 1a tumours had high nuclear BAP1 expression and all class 2 had low nuclear BAP1 expression. Fifty percent of the class 1b tumours had low nuclear BAP1 expression. Among the tumours with low nuclear BAP1 expression, 68% developed metastasis, while 9% developed metastasis among high nuclear expression. Fifty-five percent developed metastasis in tumours with high cytoplasmic expression and 42% for low cytoplasmic expression. Predictive values for metastasis (positive predictive value, negative predictive value) are as follows: (1) nuclear BAP1-IHC (68%, 91%), (2) cytoplasmic BAP1-IHC (55%, 58%), and (3) GEP (73%, 80%). Nuclear BAP1-IHC and GEP had the same accuracy rate of 77% and cytoplasmic BAP1-IHC had an accuracy of 57%. Conclusion: Low nuclear BAP1-IHC strongly correlates with GEP class 2 and was equally accurate in the prediction of metastasis.