bims-mesote 2025-11-16 papers

Issue of 2025–11–16
five papers selected by
Laura Mannarino, Humanitas Research

Transl Lung Cancer Res. 2025 Oct 31. 14(10): 4618-4627

Neoadjuvant systemic therapy for pleural mesothelioma patients: a systematic review.

Illaa Smesseim, Jo Raskin, Jacobus A Burgers.

Background: Pleural mesothelioma is an aggressive malignancy with a poor prognosis. The role of surgery in its management remains controversial, with ongoing debate regarding the definition of resectable disease. Neoadjuvant therapy aims to reduce tumor burden. This systematic review evaluates prospective neoadjuvant trials in pleural mesothelioma to identify subgroups that may benefit from this approach.
Methods: A systematic search was conducted from inception to July 01, 2024, for phase II/III prospective trials evaluating neoadjuvant systemic therapy followed by surgery in adult patients with histologically confirmed pleural mesothelioma. Data were extracted on patient characteristics, treatment regimens, surgical outcomes, survival, and adverse events.
Results: Sixteen trials were found: 861/1,184 patients (72.7%) were male, median age ranged between 57-69 years. Neoadjuvant chemotherapy was used in 15 trials and immunotherapy in one trial. Surgery was performed in 61.8% of patients, with extrapleural pneumonectomy (EPP) being the predominant approach. Median overall survival in single-arm trials was 17.4 months [95% confidence interval (CI): 15.8-19.0], n=523 for the intention-to-treat population and 21.4 months (95% CI: 19.2-23.7), n=345 for the surgery population. The phase III trial (MARS-2) comparing neoadjuvant chemotherapy plus extended pleurectomy decortication versus chemotherapy alone found a shorter median survival in the surgery and chemotherapy group {19.3 months [interquartile range (IQR), 10.0-33.7 months] vs. 24.8 months (IQR, 12.6-37.4 months), P=0.01}.
Conclusions: This review shows that the predominant neoadjuvant approach consists of platinum doublet chemotherapy, but the role of immunotherapy is being explored. Additional randomized trials are needed to determine the optimal neoadjuvant strategy and patient subgroups most likely to benefit.

Keywords: Mesothelioma; chemotherapy; immunotherapy; neoadjuvant; surgery

DOI: https://doi.org/10.21037/tlcr-2025-719

Cytopathology. 2025 Nov 10.

Comparison of Cytoplasmic and Nuclear MTAP Loss in Pleural Effusion Cytology: Correlation With Homozygous p16/CDKN2A Deletion.

Nazli Sena Şeker, Emel Yaldir, Osman Furkan Mulkem, Güntülü Ak, Muzaffer Metintaş, Selma Metintaş, Emine Dündar.

OBJECTIVE: Pleural mesothelioma (PM) is an aggressive malignancy in which pleural effusion cytology is often the first diagnostic material. MTAP immunohistochemistry, while not a stand-alone diagnostic tool, may serve as a useful adjunct when combined with other markers in the evaluation of pleural mesothelioma. However, the diagnostic relevance of nuclear versus cytoplasmic MTAP loss in cytology specimens remains unclear.
METHODS: We retrospectively analysed pleural effusion cytology samples from 48 histologically confirmed PM cases (2017-2022). Dual-colour fluorescence in situ hybridization (FISH) was performed for p16/CDKN2A, while MTAP immunohistochemistry (Proteintech 2B1G6 clone) was assessed for nuclear and cytoplasmic loss, further subclassified as focal or diffuse. Associations between MTAP loss and p16/CDKN2A deletion were evaluated using Fisher's exact test.
RESULTS: MTAP loss was observed in 21 cases (43.8%), while homozygous p16/CDKN2A deletion was detected in 33 cases (68.8%). Concurrent MTAP loss and p16/CDKN2A deletion occurred in 15 cases (31.3%). Nuclear and cytoplasmic MTAP loss were perfectly concordant in terms of presence (p < 0.001), although their staining patterns differed: diffuse nuclear loss often corresponded to focal rather than diffuse cytoplasmic loss. No significant association was observed between MTAP staining patterns and p16/CDKN2A deletion (p > 0.05).
CONCLUSIONS: Our findings demonstrate that while nuclear and cytoplasmic MTAP loss are concordant in presence, staining patterns and antibody clone selection affect correlation with p16/CDKN2A deletion. Given that pleural effusion cytology is often the initial diagnostic step in PM, standardised MTAP testing protocols are needed to ensure reproducibility and minimise false-negative interpretations, rather than implying improved diagnostic accuracy.

Keywords: MTAP; immunohistochemistry; pleural mesothelioma

DOI: https://doi.org/10.1111/cyt.70034

Environ Geochem Health. 2025 Nov 11. 47(12): 563

Healthy Mexicans exposed to erionite: a preliminary study of early-damage biomarkers for malignant pleural mesothelioma.

Liliana Ruiz-García, Nicté Figueroa-Vega, Benigno Linares-Segovia, Elva Pérez-Luque, Efraín Navarro-Olivos, Fernando Díaz-Barriga, Octavio Jiménez-Garza.

BACKGROUND: A rural community in Guanajuato State, Mexico, has presented a Malignant Pleural Mesothelioma (MPM) outbreak, one of the most rare and aggressive malignancies; such outbreak is associated with erionite exposure, a mineral responsible for the MPM epidemic in a Turkish village in the 1980. Erionite fibers are inhaled and deposited in the lungs, precluding biomonitoring its exposure in blood or urine.
METHODS: Using a case-control study design, we recruited 40 children and 20 adults, residents of Tierra Blanca de Abajo, Guanajuato, México, where erionite exposure has been documented; they were considered as the exposed group. Besides, we recruited 40 children and 22 adults from the largest city of Guanajuato state, non-exposed to the mineral (control group); a main inclusion criterion for both groups were the absence of any type of cancer (current or former). Participants were paired by sex, age and occupation. In both groups we quantified mesothelin and osteopontin serum levels for comparison.
RESULTS: In the adult exposed group, mesothelin levels were significantly higher compared to the adult control group (p = 0.003); mesothelin cut off value was: 17.92 ng/ml with 75% sensitivity and 68% specificity. Also, according to a multiple regression model where age, sex, wood smoke exposure, smoking habit, cancer family history and domestic asbestos exposure, were included, variable "residence place" was the only one showing a statistically significant association with serum mesothelin levels (β = 17.6, R2 = 0.44, p = 0.005).
CONCLUSIONS: Mesothelin may be considered an early-damage biomarker for MPM, as well as an indirect endpoint for erionite exposure.

Keywords: Early-damage biomarker; Erionite; Malignant pleural mesothelioma; Mesothelin; México; Osteopontin

DOI: https://doi.org/10.1007/s10653-025-02842-w

Mol Oncol. 2025 Nov 14.

Methylation biomarkers can distinguish pleural mesothelioma from healthy pleura and other pleural pathologies.

Janah Vandenhoeck, Nele De Meulenaere, Thomas Vanpoucke, Joe Ibrahim, Dieter Peeters, Suresh Krishan Yogeswaran, Wen Wen, Paul Van Schil, Jeroen M H Hendriks, Jo Raskin, Jan van Meerbeeck, Guy Van Camp, Ken Op de Beeck.

Pleural mesothelioma (PM) is a rare and aggressive cancer that often requires multiple diagnostic procedures before a definitive diagnosis can be made. To improve diagnostic accuracy, we developed a DNA methylation-based biomarker assay capable of distinguishing PM from healthy pleura and other pleural pathologies. Using Infinium EPIC array data, we identified 744 hypermethylated CpG sites in PM as candidate biomarkers. These were validated in silico using external datasets, yielding a high mean AUC of 0.935. Clinical validation was performed using IMPRESS, a novel bisulfite-free methylation detection technique that enables simultaneous analysis of thousands of CpG sites. A two-step classifier approach was applied: the first model differentiated tumoral from nontumoral pleura with 89.2% sensitivity and 93.5% specificity, while the second model distinguished PM from pleural metastases with 85.2% sensitivity and 100% specificity. These results demonstrate that our methylation-based biomarker panel offers a highly accurate and minimally invasive tool for differentiating PM from other pleural conditions, potentially streamlining the diagnostic process and improving clinical decision-making.

Keywords: DNA methylation; cancer biomarkers; pleural mesothelioma

DOI: https://doi.org/10.1002/1878-0261.70159

Clin Respir J. 2025 Nov;19(11): e70133

Distant Metastatic Pattern and Its Prognostic Significance in Malignant Pleural Mesothelioma: A Population-Based Study Based on a Machine Learning Model.

Jian Yu, Chi Peng, Qianwen Ye, Cong Huo, Binrui Gao, Qing Wei, Yibo Li, Kaidi Yang.

BACKGROUND: Malignant pleural mesothelioma (MPM) is an insidious and aggressive tumor, often hindering timely clinical interventions. Despite its clinical relevance, epidemiological research focusing on MPM metastases remains limited.
METHODS: We conducted a retrospective review of MPM cases with site-specific metastasis records from the Surveillance, Epidemiology, and End Results (SEER) between 2010 and 2019. Propensity Score Matching was employed to minimize bias between distant metastasis and non-distant metastasis groups. A prognostic model for predicting overall survival was established using clinical variables derived from Lasso regression. Variable importance for survival outcomes was estimated using the Random Survival Forests algorithm. The performance of the nomogram was evaluated using the receiver operating characteristic (ROC) curves and calibration plots.
RESULTS: The presence of distant metastasis significantly reduced median overall survival from 10.5 to 7 months, with further detriment observed in cases with sarcomatoid histology and without chemotherapy intervention. Multivariable analysis identified sarcomatoid subtype, T4 stage, N1+ nodal involvement, and bilateral disease as significant predictors of increased metastatic potential. Histology, surgery, and metastasis status emerged as the top three clinical variables influencing survival. The nomogram demonstrated strong discrimination and calibration for predicting the 1-year and 3-year overall survival in both training and validation cohorts. The contralateral lung was the most frequent site of distant metastasis, with lymph node metastasis presenting a significantly better prognosis than that observed in patients with metastases to other organs.
CONCLUSIONS: The large population-based analysis provides a comprehensive characterization of site-specific metastases in MPM. The identified risk factors can help stratify patients at higher risk for metastatic progression and support early, targeted clinical decision-making.

Keywords: distant metastasis; malignant pleural mesothelioma; overall survival; prognostic model; retrospective study

DOI: https://doi.org/10.1111/crj.70133