Abstract 1905P
Background
Malignant pleural mesothelioma (MPM) is an aggressive disease with few available options. Combining histological and molecular features of MPM might improve patient risk stratification. BRCA-associated protein 1 (BAP1) alterations are detected in about 60% of MPM and miRNA-31 (miR-31) is involved in the post-transcriptional regulation of BAP1 expression. We investigated the role of BAP1 and miR-31 expression in MPM patients in order to identify subgroups of MPM with more favorable biological features.
Methods
Tissue samples were obtained from 55 MPM patients treated with first-line chemotherapy at our institution. BAP1 nuclear status (retained/loss) was assessed by immunohistochemistry. Tissue miR-31 expression level was detected by quantitative RT-PCR. Overall survival (OS) and progression-free survival (PFS) were estimated using Kaplan-Meier method. Log-rank test was used to assess differences between subgroups. Multivariate COX regression analysis was utilized to evaluate predictors of survival.
Results
BAP1 loss was detected in 33 samples (60%) and resulted associated with epithelioid MPM (e-MPM) (p=0.016). At multivariate analysis, only epithelioid subtype resulted as an independent prognostic factor related to OS (p=0.001). E-MPM showed lower miR-31 levels compared to sarcomatoid/biphasic MPM (p=0.04). BAP1 loss MPM samples showed lower miR-31 levels compared to BAP1 retained MPM (p=0.013). In the e-MPM subgroup, BAP1 alone was not able to predict OS (p=0.27) and PFS (p=0.45), whereas low miR-31 levels were associated with better PFS (p=0.028), but not with OS (p=0.06). Finally, we stratified e-MPM patients according to BAP1 status and miR-31 levels together, obtaining a two-biomarker score. E-MPM patients with BAP1 loss/low miR-31 levels showed better OS and PFS compared to the BAP1 retained/high miR-31 levels subgroup (median OS: 22.6 vs 17.0 months, p=0.017; median PFS: 8.7 vs 5.1 months, p=0.020), and this was further confirmed at multivariate analysis (HR 0.45, 95% CI 0.21-0.94, p=0.034 for OS; HR 0.46, 95% CI 0.22-0.95, p=0.036 for PFS).
Conclusions
BAP1 status/miR-31 levels combination improves risk stratification in e-MPM patients and identifies a subgroup with more favorable biology and better clinical outcome.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Università Politecnica delle Marche.
Funding
Università Politecnica delle Marche.
Disclosure
All authors have declared no conflicts of interest.