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

Frontiers in Oncology 2026 May 29 [Link]

Alejandro Aviles-Salas, Norma Hernández-Pedro, Enrique Caballé-Perez, José Lucio-Lozada, César Castillo-Ruiz, José Gregorio Chanona-Vilchis, Alejandro Aranda-Gutierrez, Mario Orozco-Morales, Pedro Barrios-Bernal, Rafael Parra-Medina, Luis Cabrera-Miranda, Andrés F Cardona, Oscar Arrieta

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.