Our observations reveal a potential clinical application where BAP1 status could serve as predictive or stratification biomarker for RNR inhibition-based therapy in MPM.
In contrast, effusion SMRP levels were exclusively high in epithelioid MPM, negatively correlated with effusion TGF-β levels and did not provide prognostic information.
MTAP immunohistochemistry is an accurate and reproducible surrogate for CDKN2A fluorescence in situ hybridization in diagnosis of malignant pleural mesothelioma.
We used FISH to examine deletion status of NF2 and 9p21 and immunohistochemistry to examine expression of MTAP and BAP1 in malignant pleural mesothelioma and in reactive mesothelial hyperplasia.
Identification of BRCA1-associated protein 1 (BAP1) and cyclin-dependent kinase inhibitor 2A (CDKN2A) gene mutations in MPM have led to the development of new ancillary tests that can streamline the diagnostic pathway.
We examined IHC expression of EZH2, BAP1, and MTAP, and 9p21 FISH in MPM (n = 38) and RMH (n = 29) and analyzed the sensitivity and specificity of each detection assay for distinguishing MPM from RMH.
Unresectable MPM has a poor prognosis and limited treatment options and, as such, there is a broad range of therapeutic targets of interest, including angiogenesis, immune checkpoints, mesothelin, as well as chemotherapeutic agents.
The top hypomethylated single-CpG (cases versus controls effect size less than -0.15, p<sub>fdr</sub> < 0.05 in both the training and test sets) was detected in FOXK1 (Forkhead-box K1) gene, an interactor of BAP1 which was found mutated in MPM tissue and as germline mutation in familial MPM.
Additionally, we have seen higher EGFR expression associating with worse outcomes after Photofrin-mediated PDT for MPM, and the extensive desmoplastic reaction associated with MPM influences tumor phenotype and therapeutic response.
This phase I study investigated the safety and activity of lentiviral-transduced chimeric antigen receptor (CAR)-modified autologous T cells redirected against mesothelin (CART-meso) in patients with malignant pleural mesothelioma, ovarian carcinoma, and pancreatic ductal adenocarcinoma.
Identification of BRCA1-associated protein 1 (BAP1) and cyclin-dependent kinase inhibitor 2A (CDKN2A) gene mutations in MPM have led to the development of new ancillary tests that can streamline the diagnostic pathway.
The cell surface glycoprotein Mesothelin is overexpressed in several tumor entities and novel immune-based therapies are currently under the early clinical evaluation for the treatment of malignant pleura mesothelioma, ovarian cancer, and pancreatic cancer.
Absence of PD-L1 staining occurred in 137 (64.1%) of 214 malignant pleural mesothelioma (MPM) samples, while 77 (35.9%) of 214 were PD-L1 positive, with 50 (64.9%) of 77 showing < 50% PD-L1-expressing tumor cells.
However, significantly more MPM patients with high pulmonary asbestos fiber count (> 1 million fibers per gram [f/g]) had stromal p16 immunoreactivity than MPM of patients with low exposure (≤ 0.5 million f/g) (51.4% vs 16.7%; p = 0.035, Chi-Square).
Here, we investigated the correlation between tumour infiltrating lymphocytes (TILs) or programmed cell death ligand 1 (PD-L1) expression with overall survival (OS) in patients with MPM.
CCDC6 (coiled-coil domain containing 6) is a player of the HR response to DNA damage and has been predicted to interact with BAP1, another HR-DNA repair gene highly mutated in Malignant Pleural Mesothelioma (MPM), an aggressive cancer with poor prognosis.
The aim of our work was to evaluate the clinical significance and prognostic implications of BAP1, mesothelin and PD-L1 expression in 117 patients with a diagnosis of MPM who were diagnosed in our institution between 2002 and 2017.
BAP1 expression was a favorable predicative factor for OS in clear cell renal cell carcinoma (HR = 0.57, 95% CI: 0.47-0.69), non-small cell lung cancer (HR = 0.55, 95% CI: 0.32-0.96), and uveal melanoma (HR = 0.41, 95% CI: 0.27-0.62), while high expression of BAP1 was associated with poorer outcome in malignant pleural mesothelioma (HR = 2.03, 95% CI: 1.67-2.47).