TY - JOUR
T1 - Frequent discordance in PD-1 and PD-L1 expression between primary breast tumors and their matched distant metastases
AU - Manson, Quirine F.
AU - Schrijver, Willemijne A.M.E.
AU - ter Hoeve, Natalie D.
AU - Moelans, Cathy B.
AU - van Diest, Paul J.
N1 - 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).
PY - 2019/2/15
Y1 - 2019/2/15
N2 - 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.
AB - 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.
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - B7-H1 Antigen/metabolism
KW - Biomarkers, Tumor/metabolism
KW - Breast Neoplasms/metabolism
KW - Carcinoma, Ductal, Breast/metabolism
KW - Carcinoma, Lobular/metabolism
KW - Female
KW - Follow-Up Studies
KW - Humans
KW - Lymphatic Metastasis
KW - Middle Aged
KW - Prognosis
KW - Programmed Cell Death 1 Receptor/metabolism
KW - Survival Rate
KW - Breast cancer
KW - Metastasis
KW - Programmed death-ligand 1
KW - Programmed death-1
UR - http://www.scopus.com/inward/record.url?scp=85058416031&partnerID=8YFLogxK
U2 - 10.1007/s10585-018-9950-6
DO - 10.1007/s10585-018-9950-6
M3 - Article
C2 - 30547271
SN - 0262-0898
VL - 36
SP - 29
EP - 37
JO - Clinical & Experimental Metastasis
JF - Clinical & Experimental Metastasis
IS - 1
ER -