Trop-2 expression is associated with poor survival in pleural mesothelioma

Our plain-English summary of Trop-2 expression is associated with poor survival in pleural mesothelioma, by A. Aviles-Salas, N. Hernández-Pedro, E. Caballé-Perez, et al (Frontiers in Oncology, 2026).

The study

• Authors: A. Aviles-Salas, N. Hernández-Pedro, E. Caballé-Perez, J. Lucio-Lozada, C. Castillo-Ruiz, J.G. Chanona-Vilchis, A. Aranda-Gutierrez, M. Orozco-Morales, P. Barrios-Bernal, R. Parra-Medina, L. Cabrera-Miranda, A.F. Cardona, O. Arrieta
• Journal: Frontiers in Oncology
• Published: 2026;16:1841585
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Introduction: Pleural mesothelioma (PM) lacks reliable biomarkers to guide therapy. Trophoblast cell-surface antigen 2 (Trop-2) is targetable in epithelial cancers, but its prevalence and clinical relevance in PM remain unclear.

Methods: This retrospective cohort study selected patients with PM at the Instituto Nacional de Cancerología of Mexico from 2010 to 2022. Two independent pathologists evaluated Trop-2 positivity in histological tumor samples, defined as specific membranous staining of any intensity in ≥1% of analyzed tumor cells, equivalent to an H-score ranging 1 to 300. Median progression-free survival (mPFS) and overall survival (mOS) stratified by Trop-2 status were estimated by Kaplan-Meier method, and clinicopathologic associations were adjusted by multivariable Cox models.

Results: Among sixty cases, Trop-2 was positive in 12 cases, associated with lung (p = 0.016) and non-regional lymph nodes (p = 0.002) metastases, shorter mOS (7.9 vs 27.8 months; p = 0.021), and independently predicted of worse PFS (adjusted hazard ratio [aHR] 2.20; p = 0.048) and OS (aHR 3.79; p = 0.009). Poorer OS was also predicted by Sarcomatoid histology (aHR 6.19; p = 0.025) and PLECH score >3 (aHR 2.64; p = 0.025).

Discussion: Despite this small sample size, Trop-2 was related to adverse clinical outcomes, which may represent a key vulnerability for antibody-drug conjugates in PM, and highlight the need for its prospective standardized evaluation.

Conclusions: Trop-2 was expressed in 20% of PMs, exclusively in epithelioid histology, associated with advanced disease and poor survival outcomes. These results support the prospective evaluation of Trop-2-targeted therapies in PM.

Copyright © 2026 Aviles-Salas, Hernández-Pedro, Caballé-Perez, Lucio-Lozada, Castillo-Ruiz, Chanona-Vilchis, Aranda-Gutierrez, Orozco-Morales, Barrios-Bernal, Parra-Medina, Cabrera-Miranda, Cardona and Arrieta.

In plain English

This retrospective cohort study looked at 60 patients with pleural mesothelioma diagnosed between 2010 and 2022 at the Instituto Nacional de Cancerología in Mexico City. Two pathologists tested stored tumor samples for Trop-2, a protein some cancer drugs target. Trop-2 was found in 12 of the 60 tumors (20.0%), all of the epithelioid type. Patients with Trop-2-positive tumors more often had spread to the lung (58.3% vs 18.8%) and to non-regional lymph nodes (58.3% vs 12.5%). Their median overall survival was 7.98 months (95% CI 6.34 to not reached), against 27.86 months (16.36 to not reached) for Trop-2-negative patients. After adjustment for other factors, Trop-2 positivity was associated with worse progression-free survival (adjusted hazard ratio 2.20, 95% CI 1.01 to 4.81, p = 0.048) and worse overall survival (3.79, 95% CI 1.40 to 10.26). Asbestos exposure was documented in 35% of patients. The study found no significant association between Trop-2 and environmental exposures, including asbestos. The authors concluded that Trop-2 defines a clinically relevant subgroup. They called the findings hypothesis-generating because only 12 patients were Trop-2-positive, and noted that no patient received immunotherapy.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective, observational cohort study
• Who was studied: 60 patients with pleural mesothelioma (PM) diagnosed 2010 to 2022 at the Thoracic Oncology Unit of the Instituto Nacional de Cancerología, Mexico City. Of 80 patients identified, 20 were excluded.
• Exposure: Trop-2 protein expression in tumor tissue, measured by immunohistochemistry and scored independently by two pathologists. Asbestos exposure was recorded only as a clinical variable (present or absent); no fiber types or doses are given.
• Main results:
  • Trop-2 was positive in 12 of 60 samples (20.0%), with 100% agreement between the two pathologists.
  • None of the non-epithelioid mesothelioma cases expressed Trop-2.
  • Compared with Trop-2-negative patients, Trop-2-positive patients more often had lung metastases at baseline (58.3% vs 18.8%, p = 0.016) and non-regional lymph node (NRLN) metastases (58.3% vs 12.5%, p = 0.002).
  • Unadjusted median progression-free survival was 5.9 months in Trop-2-positive vs 11.5 months in Trop-2-negative patients. This difference was not statistically significant (p = 0.087).
  • In the adjusted (multivariate) analysis, Trop-2 positivity was associated with worse progression-free survival. Table 2 gives aHR 2.20, 95% CI 1.01 to 4.81, p = 0.048; the text rounds the interval to 1.0 to 4.8.
  • Median overall survival was 7.98 months (95% CI 6.34 to not reached) in the 12 Trop-2-positive patients, as given in Table 3 (p = 0.021).
  • Median overall survival was 27.86 months (95% CI 16.36 to not reached) in the 48 Trop-2-negative patients, as given in Table 3. The text gives these medians as 7.9 vs 27.8 months.
  • In the adjusted analysis, Trop-2-positive disease was associated with worse overall survival: aHR 3.79, 95% CI 1.40 to 10.26, p = 0.009.
  • In the adjusted analysis, sarcomatoid histology was associated with worse overall survival: aHR 6.19, 95% CI 1.26 to 30.42, p = 0.025.
  • In the adjusted analysis, a PLECH risk score above 3 was associated with worse overall survival: aHR 2.64, 95% CI 1.13 to 6.18, p = 0.025.
  • The study found no significant association between Trop-2 expression and environmental exposures, including tobacco use and asbestos exposure.
  • Documented asbestos exposure was found in 35% of the cohort.
• The authors' conclusion: The authors concluded that Trop-2 expression defines a clinically relevant pleural mesothelioma subgroup and supports trials of Trop-2-targeted therapies. They also stated that the findings should be considered hypothesis-generating and need validation in prospective multicenter cohorts.
• Limitations the authors state:
  • The sample was small (60 patients), and only 12 were Trop-2-positive, which limits the statistical power of subgroup analyses.
  • No patient received immune checkpoint inhibitors, so there are no immunotherapy outcome data.
  • Asbestos exposure may have been underreported, or affected by recall bias.
  • The recorded asbestos exposure prevalence may have been affected by referral bias.
  • The association of female sex with worse overall survival should not be overinterpreted.
  • The findings are hypothesis-generating and need prospective validation.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Biomarker, Cohort Study, Progression-Free Survival, Overall Survival, Hazard Ratio, Sarcomatoid, Histology.

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