BAP1 expression and treatment outcomes in malignant mesothelioma

Objective: Genomic studies of malignant mesothelioma (MM) have identified frequent mutations in BRCA Associated Protein 1 (BAP1), a nuclear deubiquitinase and transcriptional regulator. Immunohistochemistry (IHC) is a reliable technique to determine BAP1 molecular status. Our objective is to assess BAP1 expression and infer molecular status in a cohort from a prospective UK clinical trial (MSO1) and to determine if BAP1 status is predictive of treatment outcomes. Method: BAP1 IHC was evaluated in 79 tumour biopsies by 2 histopathologists. Cases were considered positive (wild type BAP1) if strong nuclear staining was present and negative (mutant BAP1) if absent. Results: BAP1 expression was negative in 66 of these 77 cases (86%). Conclusions: BAP1 IHC was negative in 86% of tumours suggesting a high frequency of BAP1 mutations. There was no significant correlation in clinical characteristics or outcomes with BAP1 status. When analysed by treatment subgroup, there was a trend towards a survival benefit in cases with negative BAP1 expression (BAP1 mutants) in the ASC plus vinorelbine arm, but no statistically significant difference in outcomes within any treatment arm.