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.
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.
However, the application of FISH detection of NF2 gene deletion (NF2 FISH) in differentiation of malignant pleural mesothelioma from reactive mesothelial hyperplasia has not been fully evaluated.
Since most malignant pleural mesotheliomas do not respond to anti-programmed cell death(-ligand)1 (PD-(L)1)/cytotoxic T-lymphocyte-associated protein 4 (CTLA4) therapy and given the recent finding of The Cancer Genome Atlas Study that pleural mesothelioma displays the highest expression of VISTA among all cancers studied, we examined VISTA expression in a large pleural mesothelioma cohort.
ABCB5 may represent a new target to chemosensitize MPM IC and a potential biomarker to predict the response to the first-line chemotherapy in MPM patients.
Collectively, these findings suggest that the CD70-CD27 pathway enhances the malignant phenotypes of MPM and diminishes anti-tumor immune response in patients with these neoplasms.
We further showed that deregulation of the G2-M checkpoint contributes to chemotherapy resistance, and that WEE1 inhibition synergizes with cisplatin/MTA, leading to enhanced MPM cell death in vitro and potent anti-tumor effects in vivo.
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.