Comparative Analysis of Programmed Cell Death Ligand 1 Assays in Renal Cell Carcinoma

AIMS: The importance of programmed cell death ligand 1 (PD-L1) expression has emerged in clinical trials of PD-L1 target therapy in renal cell carcinoma (RCC). This study compares PD-L1 assays in RCC. MATERIALS & METHODS: Two US Food and Drug Administration-approved PD-L1 assays (22C3 and SP142) and one research-use only antibody (E1L3N) were used in a retrospective cohort of 591 patients with RCC. PD-L1 positivity on tumour cells (TCs) and immune cells (ICs) and combined positive score (CPS) were evaluated. RESULTS: With the 22C3, SP142, and E1L3N assays, positive PD-L1 expression on TCs >/=1% was observed in 24 (4.1%), 12 (2.0%), and 16 (2.7%) cases and on ICs >/=1% was observed in 132 (22.3%), 120 (20.3%), and 65 (11.0%) cases, respectively. PD-L1 expression scores among the three assays showed moderate-high positive correlation (rho = 0.599-0.835, P <0.001). Assays appeared similar, although staining in ICs was comparatively less frequent with E1L3N. 22C3 showed highly frequent positivity in TCs. PD-L1 expression on TCs was associated with papillary type 2 RCC (P <0.001). IC infiltration and PD-L1 expression on ICs were predominantly found in clear cell and papillary type 1 RCC (P <0.05). CONCLUSIONS: Programmed death-1 (PD-1)/PD-L1 target therapy might be beneficial for patients with papillary type 2 RCC even if they are categorised as a heterogeneous group. PD-L1 assays should be carefully selected, and accurate histological subtyping of RCC is needed prior to decisions on PD-L1 testing, because of the different PD-L1 expressions observed across varying RCC subtypes.