Programmed Death-ligand 1 (PD-L1) Expression in Thymic Epithelial Tumors.

Abstract

Thymic epithelial tumors (TETs) are uncommon neoplasms of the mediastinum. The gold standard treatment is complete surgical resection which can be followed by radio/chemotherapy in selected cases. Targeted tyrosine kinase inhibition can be considered in only a limited number of aggressive or metastatic tumors as EGFR, BRAF, or c-kit mutations are rare. However, previous studies have demonstrated the efficacy of immune checkpoint inhibitors in epithelial neoplasias, such as in programmed cell death ligand 1 (PD-L1) expressing nonsmall cell lung carcinoma. Because of their rare occurrence the data on PD-L1 distribution in thymic neoplasias are limited. PD-L1 and PD-1 expression in tumor cells and tumor infiltrating immune cells was determined in TETs according to criteria published for lung carcinomas. Comparison with major clinical, pathologic, and biological features was also done. In total, 36 TETs (29 thymomas and 7 thymic carcinomas) were analyzed. PD-L1 immunohistochemical staining (Ventana PD-L1 clone SP142) was performed in all cases. The percentage of the positive tumor cells (TC value), the percentage of tumor area occupied by positive immune cells (IC value) was evaluated. Evaluation of PD-L1 expression in tumor cells showed a good reproducibility (κ-value: 0.840; Spearman r=0.966; P<0.0001). About 69% of thymomas (20/29) and 43% of thymic carcinomas (3/7) showed high positivity rate (TC≥50% or IC ≥10%), which may indicate therapeutic advantage similar to nonsmall cell lung cancers defined by the same conditions. PD-L1 expression is common in different epithelial tumors of the thymus, which suggests the potential effectiveness of drugs targeting the PD-1/PD-L1 interactions in these neoplasms.