PD-L1 in breast cancer: comparative analysis of 3 different antibodies

Hum Pathol. 2018 Feb:72:28-34. doi: 10.1016/j.humpath.2017.08.010. Epub 2017 Aug 31.

Abstract

The interaction of programmed cell death-1 and its ligand-1 (PD-L1) serves as a regulatory check against excessive immune response to antigen and autoimmunity. We compared the performance of 3 different PD-L1 antibodies (Ventana SP263, Dako 22C3, and BioCare RbMCAL10 antibodies) in 136 invasive ductal carcinoma specimens including 43 primary, 48 locally metastatic, and 46 distantly metastatic diseases. PD-L1 expression was correlated with clinicopathologic parameters including tumor size, grade, lymphovascular invasion, estrogen receptor, progesterone receptor, HER2, Ki67, molecular type, and triple-negative status. There was excellent agreement between the 3 antibodies, with highly significant κ values (P≤.001). PD-L1 expression was more likely to be associated with higher tumor grade and estrogen receptor-negative, progesterone receptor-negative, triple-negative, and highly proliferative tumors (P<.001). When we studied PD-L1 expression at 0, 1%-9%, 10%-49%, and ≥50% cutoff points by the 3 antibodies, there were 20 discordant cases between the antibodies. Sixteen were of inconsequential impact as far as low and high PD-L1 expression. The 4 differences between antibodies did exhibit an interesting pattern of expression, where there was a general agreement between the BioCare and Ventana antibodies with consistently higher PD-L1 expression compared with the Dako antibody. Given the high concordance, it is not surprising that all 3 antibodies demonstrated the same associations with all pathologic and clinical parameters studied. Standardization studies to identify reliable biomarkers that help in patient selection for immune therapy to improve the risk-benefit ratio for these drugs are still needed.

Keywords: Breast cancer; Comparative analysis; Immunohistochemistry; Invasive ductal carcinoma; Programmed cell death ligand-1; Three antibodies.

Publication types

  • Comparative Study

MeSH terms

  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / therapeutic use*
  • B7-H1 Antigen / immunology*
  • Biomarkers, Tumor / analysis
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / immunology
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Immunohistochemistry / methods
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / immunology
  • Lung Neoplasms / pathology
  • Treatment Outcome

Substances

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