Programmed death-ligand 1 expression in surgically resected thymomas

Thymomas are one of the most common neoplasms of the anterior mediastinum with limited therapeutic options, particularly in advanced stages. The molecular profiles of these tumors remain poorly investigated. This study aims to evaluate the expression of programmed death ligand 1 (PD-L1) in a selected cohort of intentionally curative resected thymomas and evaluate a possible relationship with the risk of recurrence. This retrospective bicentric study analyzed a group of patients who underwent complete thymectomy with curative intent. PD-L1 expression was assessed through immunohistochemistry using the Ventana PD-L1 assay. PD-L1 expression was assessed as low if <50% or high when ≥50%. The Kaplan-Meier method and Cox regression analysis were performed to evaluate a possible relationship between PD-L1 expression and disease-free survival. High PD-L1 expression was observed in 46.2% of patients. Overexpression of this protein was significantly associated with aggressive (B2/B3) thymomas histotypes (p<0.001). During follow-up period, 12/52 patients developed recurrence. High PD-L1 expression correlated with reduced disease-free survival with Kaplan-Meier method (p<0.001). Furthermore, PD-L1 expression more than 50% resulted to be related to a worse prognosis at multivariable Cox regression analysis (hazard ratio 5.4, 95% confidence interval 1.5-16.9, p=0.028) together with histology (p=0.044) and Masaoka-Koga stage (p=0.026). The elevated expression of PD-L1, particularly in aggressive thymoma subtypes, underscores its potential as a prognostic biomarker. These findings support the need for further research to explore the potential of immunotherapy in treating these rare malignancies.