Clinicopathologic significance of PD-L1 expression in clear cell renal cell carcinoma

Programmed cell death ligand 1 (PD-L1) is a protein that, when interacting with its receptor programmed cell death protein 1, functions as a negative regulator of the antitumor T-cell-mediated immune response. The prognostic significance of PD-L1 expression in renal cell carcinoma has been examined in previous studies; however, the results remain controversial. The clinicopathologic associations of PD-L1 expression in clear cell renal cell carcinoma were evaluated in 242 cases. PD-L1 immunoreactivity (using anti-PD-L1 monoclonal antibody, clone ZR3) was assessed separately in tumor cells and tumor-infiltrating immune cells (TIICs). PD-L1 positivity in cancer cells was defined as the presence of a membranous immunostaining pattern of any intensity in ≥ 1% of the corresponding cells, while PD-L1 positivity in TIICs was defined as membranous or cytoplasmic staining observed in ≥ 1% of the immune cells at any intensity. Associations with prespecified clinicopathologic variables were analyzed with appropriate categorical or continuous-data tests and Benjamini–Hochberg false-discovery-rate correction. Overall survival (OS) was estimated using Kaplan–Meier analysis. PD-L1 positivity was detected in tumor cells in 26.4% of specimens and in TIICs in 48.3% of specimens. After false-discovery-rate correction, tumor cells PD-L1 status was associated with tumor-size category, pathologic T stage, WHO/International Society of Urological Pathology grade, tumor necrosis, and sarcomatoid and rhabdoid transformation, while TIICs PD-L1 status was associated only with WHO/International Society of Urological Pathology grade. Kaplan–Meier analysis showed no significant difference in OS according to tumor cells PD-L1 expression (log-rank P = .2925) or TIICs PD-L1 expression (log-rank P = .9748). Compartment-specific PD-L1 expression showed exploratory associations with selected clinicopathologic characteristics; however, neither tumor cells nor TIICs PD-L1 expression was associated with OS. These findings do not establish an independent prognostic role for PD-L1 expression and warrant external validation.