bims-mesote Biomed News
on Mesothelioma
Issue of 2026–05–17
eight papers selected by
Laura Mannarino, Humanitas Research
  1. Quantitative MRI-Based T Category in Pleural Mesothelioma: Analysis of a Large Real-World Cohort.
  2. Cooperative response loops enhanced by histamine signaling during tumor-neutrophil crosstalk in pleural mesothelioma.
  3. Diagnostic Challenges in Pleural Mesothelioma.
  4. Asbestos Exposure Induces Malignant - Like Phenotypes via Minority MOMP and Displays Characteristics of Drug-Tolerant Persister Cells.
  5. Development of Mesothelioma in Organ Transplant Recipients: A Comprehensive Study of 10 Cases.
  6. Prognostic Significance of Inflammatory, Cellular, and Tumor-Specific Biomarkers in Patients With Pleural and Peritoneal Mesothelioma.
  7. Corrigendum to 'Multiomic, Histologic, and scRNA-seq Profiling of Pleural Mesothelioma Reveals Negative Prognosis Associated With a Novel Uncommitted Molecular Phenotype' [Journal of Thoracic Oncology Volume 21 Issue 4 (2026) 103529].
  8. Clinical utility and prognostic value of GATA3 in epithelioid malignant mesothelioma: a practical and cost-effective approach for resource-limited settings.
  1. Acad Radiol. 2026 May 15. pii: S1076-6332(26)00340-5. [Epub ahead of print]
    Quantitative MRI-Based T Category in Pleural Mesothelioma: Analysis of a Large Real-World Cohort.
    Ritu R Gill, William G Richards, Emanuele Mazzola, Beow Y Yeap, Raphael Bueno.
       RATIONALE AND OBJECTIVES: Accurate clinical staging in pleural mesothelioma (PM) is limited by the subjectivity of conventional imaging assessment, which introduces inter- and intraobserver variability. Tumor volume, pleural thickness and diaphragmatic thickness measurements individually prognostic - offer objective, quantifiable surrogates for locoregional tumor burden. We evaluated these Magnetic Resonance Imaging (MRI)-derived metrics to develop a reproducible quantitative clinical T-classification strategy for PM that offers objective, reproducible surrogates for tumor burden with reduced interobserver variability compared to qualitative MRI staging.
    MATERIALS AND METHODS: Patients referred for surgical evaluation of PM between 2009 and 2014 who underwent MRI using an IRB-approved protocol were included. For survival analyses, only patients with complete data and uniform treatment were analyzed. Quantitative measures included MR-derived tumor volume (VolMR), summed unidimensional pleural thickness (Psum) and Fissural and diaphragmatic thickness (Ptotal= Psum+Fmax+Dtotal) Optimal categorical thresholds were derived by survival-based optimization using the log-rank statistic, implemented via Classification and Regression Trees (CART) with 20-fold cross-validation. Predictive accuracy was assessed using univariable Cox models and C-statistics, and survival curves were generated using Kaplan-Meier estimates. Continuous variable Cox models were also constructed for VolMR and Ptotal. Analyses were stratified by surgical modality to assess robustness.
    RESULTS: Of 695 patients evaluated, 377 had eligible MR imaging. Median age was 68 years; 77% were male and 60% had epithelioid tumors. Clinical Tumor Node Metastasis staging was concordant with pathology in 52.5%, understaged in 33%, and overstaged in 14% of patients. Among evaluated metrics, diaphragmatic thickness (C-statistic = 0.5996) and total pleural thickness (0.5868) demonstrated the highest predictive accuracy. Survival curves showed strong stratification using Ptotal and VolMR. Head-to-head comparison with AJCC 8th edition qualitative T staging (C-statistic 0.6022) showed that Ptotal-based categories (C=0.6217) and VolMR-based categories (C=0.6364) provided superior survival stratification.
    CONCLUSION: Quantitative MR-derived Ptotal and VolMR improve upon qualitative T category in PM by offering objective, reproducible surrogates for tumor burden with strong prognostic stratification when appropriate cut points are applied. These metrics could support future Tumor Node Metastasis refinements and individualized treatment planning.
    Keywords:  Pleural Mesothelioma; Quantitative MR; TNM Staging
    DOI:  https://doi.org/10.1016/j.acra.2026.04.037
  2. Cell Rep. 2026 May 14. pii: S2211-1247(26)00439-0. [Epub ahead of print]45(5): 117361
    Cooperative response loops enhanced by histamine signaling during tumor-neutrophil crosstalk in pleural mesothelioma.
    Kuniyo Sueyoshi, Miwako Kakiuchi, Daisuke Komura, Hiroto Katoh, Asami Yamamoto, Susumu Kirimura, Iichiroh Onishi, Ayaka Asakawa, Hironori Ishibashi, Kenichi Ohashi, Kenichi Okubo, Shumpei Ishikawa.
      Pleural mesothelioma (PM) is an aggressive malignancy marked by substantial intratumor heterogeneity. A subset enriched in neutrophils correlates with poor prognosis, yet the underlying mechanisms and targetable pathways remain poorly defined. Here, we performed single-cell RNA sequencing (scRNA-seq) of neutrophilic PM and established matched patient-derived xenograft (PDX) models that recapitulate intratumor subpopulations with varying neutrophil infiltration. This approach enabled controlled, clinically relevant setups for analyzing neutrophil-tumor dynamics. Infiltrating neutrophils adopted a regenerative, tumor-promoting phenotype. Notably, we identified neutrophil-derived histamine as a key mediator of tumor motility and inflammatory signaling, forming a targetable feedback loop through reciprocal interactions. We further uncovered that BAP1 mutation status was linked with clinical neutrophil enrichment; CRISPR-Cas9-mediated BAP1 knockout reduced chemotactic gene expression and chromatin accessibility at regulatory regions. By revealing how tumors reprogram neutrophils, this study lays the groundwork for histamine-targeted interventions and rational patient stratification, aiming for more precise control of PM.
    Keywords:  BAP1; CP: cancer; CP: immunology; histamine; patient-derived xenograft; pleural mesothelioma; single-cell RNA sequencing; tumor microenvironment; tumor-associated neutrophils
    DOI:  https://doi.org/10.1016/j.celrep.2026.117361
  3. Cancers (Basel). 2026 Apr 25. pii: 1374. [Epub ahead of print]18(9):
    Diagnostic Challenges in Pleural Mesothelioma.
    Moshe Lapidot, Martin Sattler.
      Accurate diagnosis of PM and precise histologic subtyping are critical for optimal therapeutic decision-making, as treatment strategies-including chemotherapy, immunotherapy, or multimodality approaches-are largely subtype-dependent. Because of the several-decade latency between fiber inhalation and symptom onset, many cases are diagnosed at an advanced stage, when patients are already in poor clinical condition. As observed across multiple solid malignancies, earlier-stage diagnosis is associated with improved prognosis and expanded therapeutic options. However, the rarity of PM, the absence of validated screening strategies, and its nonspecific clinical and radiologic presentation-often mimicking both benign and metastatic pleural conditions, frequently result in diagnostic delay. Furthermore, the lack of pathognomonic histopathologic markers further complicates timely and definitive diagnosis. This review aims to delineate the epidemiologic, clinical, radiologic, and pathologic barriers that hinder accurate and early detection of PM. Current clinical evidence points to an urgent need to develop novel, validated biomarkers in PM, which will require a multidisciplinary approach.
    Keywords:  asbestos; biomarker; diagnosis; pleural mesothelioma
    DOI:  https://doi.org/10.3390/cancers18091374
  4. Carcinogenesis. 2026 May 16. pii: bgag030. [Epub ahead of print]
    Asbestos Exposure Induces Malignant - Like Phenotypes via Minority MOMP and Displays Characteristics of Drug-Tolerant Persister Cells.
    Jaylon Aggison, Cristian Medina, Siqi Wu, Naren Li, Francisco Molina-Pelayo, Jessica Ji, Mickael Farouk Gergeis, Ritika Raj, Yuan Xu, R Taylor Ripley.
      Pleural mesothelioma (PM) usually occurs many years after asbestos fiber exposure; yet the mechanisms that convert chronic damage into malignancy remain unclear. Asbestos fibers induce persistent oxidative and genomic stress that should activate apoptosis via mitochondrial outer membrane permeabilization (MOMP). MOMP normally triggers cytochrome c (cyt c) release as well as mitochondrially derived damaged-associated molecular patterns (DAMPs) resulting in downstream caspase activation which leads to DNA damage and cell death. With sublethal activation, a phenomenon known as a 'Incomplete or Minority MOMP (mMOMP)' occurs in which the cell survives the damage enabling retention and propagation of somatic mutations. We tested whether prolonged asbestos fiber exposure drives mMOMP in the mesothelial cells, MeT-5A. After culturing the cells for six months with chrysotile asbestos fibers (Chry-Asb) or crocidolite asbestos fibers (Croc-Asb), we observed an increase in clonogenicity, migration, and invasion, suggesting that transformation to a malignant-like phenotype was occurring. Next, we found increases in ROS production, cyt c release, and γH2AX phosphorylation without activation of caspase-3 and apoptotic induction. These cellular features are consistent with mMOMP. Additionally, an anti-apoptotic, mitochondrial protein, Myeloid Cell Leukemia (MCL)-1 was upregulated by asbestos and enabled mMOMP by preventing MOMP. Furthermore, we observed that asbestos-induced mMOMP was associated with features of drug-tolerant persister cells (DTPs). mMOMP facilitates avoidance of apoptosis by mesothelial cells while acquiring malignant traits. Our study indicates that mMOMP is a mechanism that promotes carcinogenesis, mitochondrial changes, and metabolic reprogramming. These findings offer a foundation for future therapeutic investigations.
    Keywords:  Asbestos; Mesothelioma; Mitochondria; incomplete MOMP
    DOI:  https://doi.org/10.1093/carcin/bgag030
  5. Arch Pathol Lab Med. 2026 May 11. pii: earpa.2025-0385-OA. [Epub ahead of print]
    Development of Mesothelioma in Organ Transplant Recipients: A Comprehensive Study of 10 Cases.
    Huihua Li, Andre E Nel, Sergio Pina-Oviedo, John M Carney, Carolyn H Glass, Thomas A Sporn, Richard Attanoos, Aliya N Husain, Sonja Klebe, Beiyu Liu, Victor L Roggli, Elizabeth N Pavlisko.
       Context.—: The development of malignancy after organ transplant has been well recognized as a complication of long-term posttransplant immunosuppression. Although rare cases of mesothelioma have been reported in transplant recipients, a comprehensive review of this malignancy in the context of immune suppression is lacking.
    Objective.—: To provide a comprehensive review of 10 retrospective mesothelioma cases developed after transplant.
    Design.—: This retrospective study is composed of 10 mesothelioma cases, collected at multiple institutions following solid organ or bone marrow transplant. Patients' clinicopathologic characteristics, histologic features of tumors, and disease prognosis were investigated.
    Results.—: All 10 patients were males, with a median age of 64 years at the time of mesothelioma diagnosis (range, 57-77 years). The mesothelioma development followed transplant of the kidney (3), liver (3), heart (2), lung (1), and bone marrow (1), among which the bone marrow and kidney recipients showed longer intervals between transplant and development of mesothelioma. Pleural mesothelioma (9) was more common than peritoneal mesothelioma (1). Subtypes of mesothelioma observed included epithelioid (3), biphasic (3), and sarcomatoid (4). Notably, the incidences of sarcomatoid and biphasic subtypes were higher in transplant patients compared with the general population. No association between any subtype of mesothelioma and organ transplanted was observed. Transplant patients passed away shortly (median survival, 10.5 months) after the development of mesothelioma; epithelioid subtype showed the best prognosis, followed by biphasic and sarcomatoid subtypes.
    Conclusions.—: Although rare, mesothelioma represents another malignancy occurring in the posttransplant population, emphasizing the importance of immune surveillance in cancer development.
    DOI:  https://doi.org/10.5858/arpa.2025-0385-OA
  6. Clin Lung Cancer. 2026 Apr 15. pii: S1525-7304(26)00056-2. [Epub ahead of print]
    Prognostic Significance of Inflammatory, Cellular, and Tumor-Specific Biomarkers in Patients With Pleural and Peritoneal Mesothelioma.
    Keval Yerigeri, Manjistha Sengupta, Jingli Zhang, Jeevan Puthiamadathil, Raffit Hassan.
       BACKGROUND: Mesothelioma is an aggressive malignancy with poor outcomes, particularly when diagnosed at advanced stages. This study evaluated the prognostic value of tumor-specific biomarkers: soluble mesothelin-related peptide (SMRP), megakaryocyte potentiating factor (MPF) and CA125; inflammatory markers: C-reactive protein (CRP) and fibrinogen; cellular markers: platelet count and neutrophil-to-lymphocyte ratio (NLR) in patients with pleural (MPM) and peritoneal mesothelioma (MPeM).
    METHODS: A total of 414 patients including 241 MPM, 153 MPeM and 20 with mesothelioma at other body sites were enrolled in the Natural History Protocol (NCT01950572) at the National Cancer Institute. Blood samples collected at enrollment were assessed for biomarker levels and based on their expression levels patients were stratified into quartiles. Kaplan-Meier survival curves were plotted, and median overall survival (mOS) was compared between groups.
    RESULTS: For all the biomarkers evaluated, there was a significant decrease in mOS in the high expression cohorts. The mOS in years in low versus high expression cohorts being: SMRP (3 vs. 0.7), MPF (3.7 vs. 0.7), CA125 (1.6 vs. 0.8), CRP (4.1 vs. 0.4), fibrinogen (4.1 vs. 0.6), platelet count (1.4 vs. 0.8) and NLR (2.1 vs. 0.7). When analyzed separately, the pleural and peritoneal cohorts showed similar trends. Strong correlations existed between SMRP and MPF (r = 0.84), as well as CRP and fibrinogen (r = 0.86).
    CONCLUSIONS: Biomarkers such as SMRP, MPF, CA125, CRP, fibrinogen, platelet count and NLR can independently predict overall survival in mesothelioma. These biomarkers can therefore provide prognostic information for these patients and help guide treatment strategies.
    Keywords:  C-reactive protein; CA125; Megakaryocyte potentiating factor; Mesothelin; Platelet counts
    DOI:  https://doi.org/10.1016/j.cllc.2026.04.005
  7. J Thorac Oncol. 2026 May 15. pii: S1556-0864(26)00368-0. [Epub ahead of print] 103915
    Corrigendum to 'Multiomic, Histologic, and scRNA-seq Profiling of Pleural Mesothelioma Reveals Negative Prognosis Associated With a Novel Uncommitted Molecular Phenotype' [Journal of Thoracic Oncology Volume 21 Issue 4 (2026) 103529].
    David T Severson, Samuel Freyaldenhoven, Benjamin Wadowski, Yin P Hung, Travis Hughes, Beow Y Yeap, William G Richards, Sanna Laaksonen, Lucian Chirieac, Matthew B Couger, Roderick V Jensen, Ahmed A Sadek, Ilkka Ilonen, Kimberly Vermilya, Simona Innocenti, Stephanie L Korle, Julianne S Barlow, Jamie Anderson, Jason Meyerovitz, Vivian Wang, Mary N Dao, Alex K Shalek, Assunta De Rienzo, Raphael Bueno.
      
    DOI:  https://doi.org/10.1016/j.jtho.2026.103915
  8. J Clin Pathol. 2026 May 14. pii: jcp-2026-210673. [Epub ahead of print]
    Clinical utility and prognostic value of GATA3 in epithelioid malignant mesothelioma: a practical and cost-effective approach for resource-limited settings.
    Dina Moustafa Thabit, Dalia M Thabet.
       AIMS: Distinguishing epithelioid malignant mesothelioma (EMM) from poorly differentiated lung adenocarcinoma (PD-LUAD) remains challenging, particularly when 21.7% of PD-LUADs lack lineage-specific markers (thyroid transcription factor-1 (TTF-1)/Napsin A), creating a diagnostic blind spot. While GATA-binding protein 3 (GATA3) is established in sarcomatoid mesothelioma, its complementary diagnostic value and prognostic relevance in EMM are not well defined.
    METHODS: This retrospective study analysed 115 tissue specimens (55 EMMs; 60 PD-LUADs). Immunohistochemistry for GATA3, calretinin, Wilms' tumour gene 1 (WT-1), TTF-1, Napsin A and pan-cytokeratin was performed. Results were correlated with clinicopathological parameters and overall survival (OS) using Kaplan-Meier and multivariate Cox regression analyses.
    RESULTS: GATA3 was expressed in 78.2% of EMM but only 6.7% of PD-LUAD cases (p<0.001). Although not specific enough for standalone diagnosis, GATA3 provided meaningful complementary value: in TTF-1/Napsin A-negative PD-LUAD, GATA3 remained negative in 92.3%, helping to exclude EMM when used within a broader panel. Incorporating GATA3 with calretinin and WT-1 improved panel sensitivity to 96.4% while maintaining 100% specificity.High GATA3 expression in EMM correlated significantly with advanced T stage, higher International Mesothelioma Interest Group stage and poor functional status (Karnofsky performance status/Eastern Cooperative Oncology Group). Multivariate analysis identified GATA3 expression (p=0.037), smoking (p=0.041) and clinical T stage (p<0.001) as independent predictors of shorter OS. A qualitative inverse relationship between tumorous GATA3 and GATA3-positive tumour-infiltrating lymphocytes was also noted.
    CONCLUSIONS: GATA3 serves as a useful adjunct within established immunohistochemical panels, particularly in resolving ambiguity in double-negative PD-LUAD. Beyond its supportive diagnostic role, GATA3 demonstrates independent prognostic significance and may reflect underlying immune-microenvironmental features, meriting further exploration in biomarker-guided therapeutic stratification.
    Keywords:  IMMUNOHISTOCHEMISTRY; Lung Neoplasms; PLEURA
    DOI:  https://doi.org/10.1136/jcp-2026-210673
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