Expression of PD-1 and PD-L1 in thymic epithelial neoplasms.

Abstract

Thymic epithelial neoplasms are rare tumors that are difficult to diagnose and treat. Programmed death 1 (PD-1) receptor and its ligand (PD-L1) are expressed by various malignancies and are considered a prognostic factor and immunotherapeutic target. We examined the expression of both antibodies in 100 thymic epithelial neoplasms to assess their use as a biomarker and to correlate their expression with clinicopathological parameters. Whole-tissue sections of 74 thymomas and 26 thymic carcinomas were examined. Expression of PD-1 and PD-L1 was evaluated by immunohistochemistry and scored by the percentage of positive T-cells or tumor cells, respectively. Cases with strong membranous reactivity of the antibody in ≥5% of T-cells (PD-1) or tumor cells (PD-L1), respectively, were considered positive. Expression of PD-1 was detected in 52/100 cases (52%) including 6/26 thymic carcinomas (23%) and 46/74 thymomas (62%). PD-L1 was positive in 61/100 cases (61%) including 14/26 thymic carcinomas (54%) and 47/74 thymomas (64%). A total of 82 cases (82%) showed expression of PD-1 or PD-L1. PD-1⁺ cases were associated with higher stage in thymic carcinoma (P=0.01) and PD-1^- cases with thymic carcinoma histology (P=0.0014), whereas PD-L1⁺ cases were associated with neoadjuvant therapy in thymoma (P=0.0065). There was no statistical difference between PD-1 or PD-L1 expression status and other clinicopathological parameters including overall survival. PD-1 and/or PD-L1 are expressed in up to 82% of thymic epithelial neoplasms. These results confirm that these tumors should be considered for PD-1/PD-L1-targeted therapy, however their predictive value in terms of prognosis remains uncertain.