The frequency of BAP1 and MTAP loss in Benign Asbestos-associated Pleural Inflammation

Abstract

<b>Introduction:</b> Malignant Pleural Mesothelioma (MPM) is associated with loss of tumour suppressor genes, including BAP1 and CDKN2A. In MPM biopsies, these can be identified by loss of BAP1 and MTAP expression using immunohistochemistry, with recent studies reporting near-100% specificity. However, genomic events precede invasive MPM in asbestos-induced mouse models, and small human studies (n&lt;12) report rare cases of BAP1/MTAP loss progressing to MPM (‘mesothelioma-in-situ’). Here we report the frequency of BAP1 and MTAP loss in a cohort with robustly benign asbestos-associated pleural inflammation. <b>Methods:</b> A single centre retrospective cohort study was performed. Cases were identified via the local pathology database. Eligibility required 1) asbestos exposure or typical imaging, e.g., plaques 2) compatible histology (benign fibrinous pleurisy, non-specific pleuritis, atypical mesothelial proliferation 3) No MPM diagnosis over at least 2-years follow-up 4) available tissue. FFPE tissue blocks were visually assessed for pleural tissue by an expert pathologist. BAP1 and MTAP IHC were visually scored as retained or loss. <b>Results:</b> <b>Conclusion:</b> BAP1 and MTAP loss were observed at low but important frequencies (2% and 5%). It is unclear whether these represent mesothelioma-in-situ that will later progress. The evolution of MPM will be evaluated further using paired sequential biopsies in the PREDICT-Meso accelerator network.