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

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. 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. 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). 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. 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.