Frequent discordance in PD-1 and PD-L1 expression between primary breast tumors and their matched distant metastases
Manson, Quirine F.; Schrijver, Willemijne A.M.E.; ter Hoeve, Natalie D.; Moelans, Cathy B.; van Diest, Paul J.
(2019) Clinical & Experimental Metastasis, volume 36, issue 1, pp. 29 - 37
(Article)
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
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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.
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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, Oncology, Cancer Research, Research Support, Non-U.S. Gov't, Journal Article
ISSN: 0262-0898
Publisher: Springer Netherlands
Note: Funding Information: We would like to thank the tissue facility of the UMCU for their help with the immunohistochemical stainings. Funding Information: Funding Quirine F. Manson is financially supported by the Dutch Cancer Society, Grant No. KUN2014-7032. Publisher Copyright: © 2018, The Author(s).
(Peer reviewed)