Frequent discordance in PD-1 and PD-L1 expression between primary breast tumors and their matched distant metastases

Quirine F. Manson, Willemijne A.M.E. Schrijver, Natalie D. ter Hoeve, Cathy B. Moelans, Paul J. van Diest*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

42 Citations (Scopus)
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Abstract

Programmed death-1 (PD-1) is an immune checkpoint that is able to inhibit the immune system by binding to its ligand programmed death-ligand 1 (PD-L1). In many cancer types, among which breast cancer, prognostic and/or predictive values have been suggested for both PD-1 and PD-L1. Previous research has demonstrated discrepancies in PD-L1 expression between primary breast tumors and distant metastases, however data so far have been scarce. We therefore evaluated immunohistochemical expression levels of PD-1 and PD-L1 in primary breast tumors and their paired distant metastases, and evaluated prognostic values. Tissue microarrays from formalin-fixed paraffin-embedded resection specimens of primary breast cancers and their matched distant metastases were immunohistochemically stained for PD-1 and PD-L1. PD-1 was available in both primary tumor and metastasis in 82 patients, and PD-L1 in 49 patients. PD-1 was discrepant between primary tumor and metastasis in half of the patients (50%), PD-L1 on tumor cells was discrepant in 28.5%, and PD-L1 on immune cells in 40.8% of the patients. In primary tumors there was a correlation between PD-1 positivity and a higher tumor grade, and between immune PD-L1 and ER negativity. In survival analyses, a significantly better overall survival was observed for patients with PD-L1 negative primary breast tumors that developed PD-L1 positive distant metastases (HR 3.013, CI 1.201–7.561, p = 0.019). To conclude, PD-1 and tumor and immune PD-L1 seem to be discordantly expressed between primary tumors and their matched distant metastases in about one-third to a half of the breast cancer patients. Further, gained expression of PD-L1 in metastases seems to indicate better survival. This illustrates the need of reassessing PD-1 and PD-L1 expression on biopsies of distant metastases to optimize the usefulness of these biomarkers.

Original languageEnglish
Pages (from-to)29-37
Number of pages9
JournalClinical & Experimental Metastasis
Volume36
Issue number1
DOIs
Publication statusPublished - 15 Feb 2019

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • B7-H1 Antigen/metabolism
  • Biomarkers, Tumor/metabolism
  • Breast Neoplasms/metabolism
  • Carcinoma, Ductal, Breast/metabolism
  • Carcinoma, Lobular/metabolism
  • Female
  • Follow-Up Studies
  • Humans
  • Lymphatic Metastasis
  • Middle Aged
  • Prognosis
  • Programmed Cell Death 1 Receptor/metabolism
  • Survival Rate
  • Breast cancer
  • Metastasis
  • Programmed death-ligand 1
  • Programmed death-1

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