Comparative analysis of programmed cell death ligand 1 assays in renal cell carcinoma

Histopathology. 2020 Jul;77(1):67-78. doi: 10.1111/his.14054. Epub 2020 Jun 7.

Abstract

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.

Methods and results: 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. 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 (ρ = 0.599-0.835, P < 0.001). Assays appeared similar, although staining in ICs was comparatively less frequent with E1L3N. 22C3 showed 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 may 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 expression observed among varying RCC subtypes.

Keywords: 22C3; SP142; immunotherapy; programmed cell death ligand 1; renal cell carcinoma.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • B7-H1 Antigen / analysis*
  • Biomarkers, Tumor / analysis*
  • Carcinoma, Renal Cell*
  • Cohort Studies
  • Female
  • Humans
  • Immunohistochemistry / methods*
  • Kidney Neoplasms*
  • Male
  • Middle Aged
  • Retrospective Studies
  • Young Adult

Substances

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human