Association of PD-L1, PD-L2, and Immune Response Markers in Matched Renal Clear Cell Carcinoma Primary and Metastatic Tissue Specimens

Am J Clin Pathol. 2019 Jan 7;151(2):217-225. doi: 10.1093/ajcp/aqy141.

Abstract

Objectives: Immune checkpoint therapy has been promising in renal cell carcinoma, but no validated clinically relevant biomarkers exist. Metastatic deposits may have discordant biomarker expression.

Methods: Fifty matched pairs of primary and metastatic kidney tumors were evaluated via immunohistochemistry for immune checkpoint proteins PD-1, PD-L1, and PD-L2 and the T-cell and macrophage surface markers CD3, FOXP3, and CD163. Semiquantitative scores incorporating prevalence of both tumor and nontumor labeling were compared between metastatic and primary kidney tumor specimens.

Results: A large minority of patients had discordant expression of PD-1 (31.2%), PD-L1 (22.5%), or PD-L2 (21.5%) between primary and metastatic sites. The expression of the novel marker PD-L2 correlated with both PD-1 (r = 0.47, P = .02) and PD-L1 (r = 0.67, P < .001) in metastatic deposits.

Conclusions: This study demonstrates that renal clear cell carcinoma primary tumors and metastatic deposits have some discordance in the expression of PD-L1, PD-1, and PD-L2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • B7-H1 Antigen / metabolism*
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Renal Cell / metabolism*
  • Carcinoma, Renal Cell / pathology
  • Female
  • Humans
  • Immunity, Humoral*
  • Immunohistochemistry
  • Kidney Neoplasms / metabolism*
  • Kidney Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Programmed Cell Death 1 Ligand 2 Protein / metabolism*

Substances

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • PDCD1LG2 protein, human
  • Programmed Cell Death 1 Ligand 2 Protein