Prognostic Significance of B7-H3, TROP2, and p16 Expression in Pleural Mesothelioma: Clinicopathological Correlations and Survival Outcomes

Background: Pleural mesothelioma (PM) is an aggressive malignancy with considerable biological heterogeneity and few established prognostic biomarkers. We evaluated the clinicopathological and prognostic relevance of B7-H3, TROP2, and p16 expression in PM. Methods: This retrospective study included 50 patients with histologically confirmed PM diagnosed between 2016 and 2025. Immunohistochemical expression of B7-H3, TROP2, and p16 was evaluated using an immunoreactivity scoring system. Associations with clinicopathological features were examined, and overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan–Meier and Cox proportional hazards methods. Results: High B7-H3, TROP2, and p16 expression was observed in 78%, 18%, and 20% of tumors, respectively. High B7-H3 expression was significantly associated with asbestos exposure, chemotherapy, and tumor stage. Patients with high B7-H3 expression had shorter median OS (11.0 vs. 42.0 months; p < 0.001) and PFS (11.0 vs. 40.0 months; p = 0.004) than those with negative/low expression. Neither TROP2 nor p16 expression was significantly associated with survival. In a parsimonious multivariable Cox model, high B7-H3 expression remained significantly associated with poorer OS after adjustment for disease stage (HR = 4.42, 95% CI: 1.29–15.21, p = 0.018). Conclusions: B7-H3 is frequently expressed in PM and was associated with poorer survival, including after adjustment for disease stage. These findings support further investigation of B7-H3 as a potential prognostic biomarker and therapeutic target in PM.