Prognostic relevance of programmed cell death protein 1/programmed death-ligand 1 pathway in thymic malignancies with combined immunohistochemical and biomolecular approach

Background: The aim of the study was to investigate Programmed cell Death protein 1 (PD-1) and Programmed Death-Ligand 1 (PD-L1) and their mRNA expression in thymic epithelial tumors (TETs). Research design and Methods: We analyzed 68 samples of formalin-fixed paraffin embedded tissue (63 thymomas and 5 thymic carcinomas). PD-1 and PD-L1 protein expression was evaluated by immunohistochemistry and mRNA expression was evaluated by Real Time-PCR. Results: M/F ratio was 33/35, and median age was 60.5 years. 20 patients had Myasthenia Gravis (MG). In the subgroup with large tumors (>5 cm), PD-L1 mRNA overexpression was significantly associated with worse prognosis vs. patients with no mRNA overexpression (p =0.0083) and simultaneous PD-L1 immunostaining (>1%); PD-L1 mRNA overexpression was significantly associated with worse prognosis, respect to patient with PD-L1 negative immunostaining and no PD-L1 mRNA overexpression (p = 0.0178). The elderly patients (> 60 years) with large tumors showed worse prognosis (p = 0.0395). PD-L1 immunostaining (>50%) resulted significantly associated with MG. Conclusions: Our data suggest the potential involvement of the PD-1 and PD-L1 pathway in TETs progression. According to our results, it may be helpful to design future trials with anti-PD-1 drugs to establish high-risk patients after surgery.