Programmed Death-Ligand 1 (PD-L1) Is a Potential Biomarker of Disease-Free Survival in Papillary Thyroid Carcinoma: a Systematic Review and Meta-Analysis of PD-L1 Immunoexpression in Follicular Epithelial Derived Thyroid Carcinoma.

The expression of programmed death-ligand 1 (PD-L1) is an established prerequisite for the administration of checkpoint inhibitor therapy and is of prognostic value in several cancer types. Data concerning the potential effect of PD-L1 on the prognosis of thyroid carcinoma are limited. Therefore, this study aimed to provide a systematic review of the published data on this topic. The literature was reviewed to gather and quantify evidence on the prognostic role of PD-L1 in follicular epithelial derived thyroid carcinomas and determine its association with clinicopathological parameters. A meta-analysis was performed using the DerSimonian-Laird random-effects model. The quality of studies was evaluated with the Newcastle-Ottawa Scale and a modified GRADE approach used to rate the quality of evidence. Out of 445 papers, 18 were included and 15 provided adequate data for meta-analysis. The quality of evidence ranged from low to high. PD-L1 expression was significantly associated with a reduced disease-free survival (DFS) (RR 1.63, CI 1.04-2.56, p = 0.03, I2 68%, τ2 0.19 and HR 1.90, CI 1.33-2.70, p< 0.001, I2 0%, τ2 0.00); however, no association was found with the overall survival (OS). Furthermore, a significant association was found with respect to underlying chronic lymphocytic thyroiditis and BRAFV600E mutation status in papillary thyroid carcinomas. In the subgroup analysis, the association of PD-L1 and DFS remained strong in papillary thyroid carcinoma when compared with dedifferentiated thyroid carcinomas (anaplastic and poorly differentiated thyroid carcinomas) that failed to demonstrate a significant association with respect to PD-L1. These findings underscore the role of PD-L1 immunohistochemistry as a potential prognostic biomarker of disease recurrence in patients with papillary thyroid carcinoma.