bims-mesote 2026-09-27 papers

Issue of 2026–09–27
three papers selected by
Laura Mannarino, Humanitas Research

Histopathology. 2026 Sep 21.

Low frequency of MTAP co-deletion with CDKN2A in peritoneal mesothelioma suggests an independent diagnostic role for MTAP.

Andrea Quaranta, Donato Mancini, Concetta Caporusso, Andrea Marzullo, Luigi Vimercati, Cecilia Salzillo, Federica Pezzuto, Fiorella Calabrese, Gabriella Serio.

AIMS: Loss of MTAP expression by immunohistochemistry (IHC) is widely used as a surrogate for CDKN2A homozygous deletion (HD) in pleural mesothelioma (PM), but its diagnostic value in peritoneal mesothelioma (PeM) is less well defined. We investigated whether the observed limited reliability of MTAP IHC in PeM reflects a lower frequency of MTAP/CDKN2A co-deletion.
METHODS AND RESULTS: Twenty-four PeMs selected from a previously characterized cohort according to CDKN2A and MTAP status underwent MTAP fluorescence in situ hybridization (FISH) using a custom-made probe. Twenty-five PMs and 10 reactive mesothelial proliferations (RMPs) were included as external controls. MTAP IHC, CDKN2A FISH and MTAP FISH were evaluated, and concordance was assessed using Cohen's kappa. In PM, MTAP IHC showed perfect concordance with MTAP FISH (kappa = 1.00; p < 0.001) and good concordance with CDKN2A FISH, as did MTAP FISH (kappa = 0.613; p = 0.002). MTAP IHC and FISH showed 100% specificity and 68.8% sensitivity for CDKN2A HD by FISH. In PeM, MTAP IHC remained highly concordant with MTAP FISH (kappa = 0.83; p = 0.001), whereas concordance with CDKN2A FISH was poor and not significant for both MTAP IHC (kappa = 0.21; p = 0.36) and MTAP FISH (kappa = 0.33; p = 0.17). In PeM, MTAP FISH showed 75% specificity and 62.5% sensitivity, MTAP IHC showed 75% specificity and 50% sensitivity for CDKN2A HD by FISH. All RMPs showed complete agreement and full specificity and sensitivity across all assays.
CONCLUSIONS: Our findings indicate that in PeM, MTAP, although a less reliable surrogate for CDKN2A status, may serve as an independent adjunct diagnostic marker. The low concordance between MTAP and CDKN2A alterations suggests a lower rate of co-deletion and points to potential site-specific molecular differences.

Keywords: CDKN2A FISH; MTAP; biomarker; mesothelioma; molecular pathology

DOI: https://doi.org/10.1111/his.70276

Cancers (Basel). 2026 Sep 16. pii: 2990. [Epub ahead of print]18(18):

Nuclear Factor-κB Signaling in Murine Models of Malignant Pleural Mesothelioma.

Benteng Deng, Ioanna Giopanou, Lori Asarian, Ioannis Lilis, Jianlong Jia, Marina Lianou, Dimitris Simoglou, Giannoula Ntaliarda, Tonia A Adamide, Isis E Fernandez, Georgios T Stathopoulos.

BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive asbestos-associated cancer in which inflammatory pathways may contribute to tumor behavior. NF-κB signaling is a central mediator of inflammation and cell survival, but the relative contributions of its associated enzymes, IKKα- and IKKβ, in MPM models remain incompletely understood.
METHODS: We characterized the involvement of IKKα- and IKKβ in tumor formation using several in vitro approaches and the intrapleural or subcutaneous delivery of three murine MPM cell models (AB2, AE17 and KPM1). The experimental approaches included shRNA silencing of Chuk and Ikbkb-the genes encoding the activity of IKKα- and IKKβ-and tumor growth, apoptosis and colony formation measurements. Exploratory pathway and transcriptional analyses were carried out following RNA-sequencing of our murine cell lines and a publicly available human gene expression dataset was also analyzed to provide complementary evidence.
RESULTS: Activation of the IKKα- and IKKβ was confirmed in the AB2, AE17 and KPM1 cell lines. Silencing both Chuk and Ikbkb decreased target and cross-target transcripts and metabolic growth. Importantly, Chuk silencing was associated with increased early apoptotic staining in AE17 and KPM1 cells, increased late apoptotic staining in AE17 cells and reduced colony formation in all cell models. Furthermore, Chuk-associated effects on tumor burden and activity were more notable than Ikbkb-associated effects in both intrapleural and subcutaneous tumor formation parameters. Finally, while canonical NF-κB gene-set clustering in both human and murine tumor samples identified specific and shared pathways and transcriptional profiles supporting the in vitro murine assay findings, the analyses remained exploratory and did not specifically establish target dependency.
CONCLUSIONS: Our data support the involvement of IKK/NF-κB-associated signaling in cell survival, clonogenicity and tumor growth in several MPM murine cell models and identify Chuk-related signaling as a promising target in future studies.

Keywords: Chuk; IKKα; IKKβ; Ikbkb; NF-κB; RNA-seq; malignant pleural mesothelioma; murine tumor models; shRNA

DOI: https://doi.org/10.3390/cancers18182990

Cancers (Basel). 2026 Sep 17. pii: 3018. [Epub ahead of print]18(18):

Comparative Gene Expression Analysis of Epithelioid Pleural and Peritoneal Mesothelioma.

Rebecca Sparavelli, Anello Marcello Poma, Pinuccia Faviana, Clara Ugolini, Marco Lucchi, Piero Vincenzo Lippolis, Greta Alì, Rossella Bruno.

Background/Objectives: Pleural and peritoneal mesothelioma (PL and PE) are aggressive diseases, accounting for 68.0-92.4% and 6.9-24.1% of all cases. To improve both diagnosis and management of these patients, a deeper knowledge and characterization of the molecular background are necessary. Although molecular profiling of PL has been largely investigated in recent years, much less is known about the genomic landscape of PE, due to its rarity. Here, we aim to compare gene expression profiling of pleural and peritoneal mesothelioma to underline main differences and to identify new potential histotype-specific biomarkers. Methods: We performed a gene expression analysis of 32 epithelioid PL and 21 epithelioid PE cases, diagnosed from 2017 to 2023 at the University Hospital of Pisa, using an nCounter custom panel including 117 target genes known for their crucial role in cancer. Results: PE, compared to PL, showed different expression levels of genes related to extracellular matrix modification (ECM), as collagen alteration, pro-inflammatory and angiogenic response (mediated by NF-κB). In detail, in PE we observed a significant upregulation of metalloproteinase-1 (MMP1), E-selectin (SELE), pappalysin-1 (PAPPA), estrogen receptor-2 (ESR2) and transportin-2 (TNPO2); and a downregulation of pyruvate kinase (PKM). Furthermore, BAP1 loss was associated with distinct gene deregulation in PE and PL; the only exception was ASS1 upregulation, which was observed in both histologies. These insights may help refine the utility of BAP1 as a biomarker. Conclusions: Deregulated genes in PE deserve further investigation as potential biomarkers, according to their biological role. In fact, MMPs and PAPPA impact migration ability and angiogenic response of mesothelioma, while PKM and ESR2 are usually investigated for their involvement in reprogramming of energy metabolism. The identification of histotype-specific biomarkers is warranted to improve mesothelioma management.

Keywords: NanoString; extracellular matrix; gene expression; mesothelioma; molecular profile; peritoneal; pleural; tumor microenvironment

DOI: https://doi.org/10.3390/cancers18183018