Loss of BAP1 expression in mesothelioma cases diagnosed locally

Abstract

Mesothelioma is a malignancy arising from mesothelial cells, often occurring in the pleura of the lungs due to asbestos exposure. The current method of diagnosis is reliant on histomorphology, and differential diagnosis from metastatic mimickers and benign lesions may be difficult. The currently available immunohistochemistry (IHC) staining markers have a limited role in helping to distinguish between malignant and reactive lesions. BRCA1 associated Protein-1 (BAP1) is a tumour suppressor protein that is found in nuclei and regulates gene translation and repair. Studies have confirmed that BAP1 expression is lost in a significant percentage of mesothelioma cases. This study aimed to optimise and validate BAP1 IHC by using two different primary antibody clones (C-4 and BSB-109), and test mesothelioma cases diagnosed locally to establish the percentage of mesotheliomas characterised by BAP1 loss. The total number of cases tested were 55 mesothelioma cases, along with 10 cases of pleural metastatic tumours and 10 hyperplastic benign mesothelial cases, which were used as controls. All 20 control cases resulted positive for BAP1 expression, as expected. The majority of the mesothelioma cases were diagnosed in males (female to male ratio of 1:12.75), and the mean age at diagnosis was 74 years. Both histological and cytological samples were used. The most common mesothelioma site was the pleura, and the most frequent subtype was epithelioid. The percentage of loss of BAP1 in the mesothelioma cases analysed was 58.18%, which was within the range found in literature. The diagnostic use antibody clone BSB-109 and the research use antibody clone C-4 yielded the same results. This study served as rigorous validation for the diagnostic use of BAP1 IHC as recommended in the 2021 World Health Organisation (WHO) classification of thoracic tumours.