TY - JOUR
T1 - Assessment of PD-L1 expression across breast cancer molecular subtypes, in relation to mutation rate, BRCA1-like status, tumor-infiltrating immune cells and survival
AU - Sobral-Leite, Marcelo
AU - Van de Vijver, Koen
AU - Michaut, Magali
AU - van der Linden, Rianne
AU - Hooijer, Gerrit K.J.
AU - Horlings, Hugo M.
AU - Severson, Tesa M.
AU - Mulligan, Anna Marie
AU - Weerasooriya, Nayana
AU - Sanders, Joyce
AU - Glas, Annuska M.
AU - Wehkamp, Diederik
AU - Mittempergher, Lorenza
AU - Kersten, Kelly
AU - Cimino-Mathews, Ashley
AU - Peters, Dennis
AU - Hooijberg, Erik
AU - Broeks, Annegien
AU - van de Vijver, Marc J.
AU - Bernards, Rene
AU - Andrulis, Irene L.
AU - Kok, Marleen
AU - de Visser, Karin E.
AU - Schmidt, Marjanka K.
N1 - Funding Information:
ONCOPOOL was supported by a European Commission Framework 5 Project Grant. RATHER was supported by European Commission Framework 7 Project Grant. MSL received a scholarship from Science without Borders - CAPES. Funding of group Schmidt at the Netherlands Cancer Institute provided a partial grant and covered the IHC staining and image analysis. This work was also supported by grant UM1 CA164920 from the USA National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the USA Government or the BCFR. I.L.
Funding Information:
ONCOPOOL was supported by a European Commission Framework 5 Project Grant. RATHER was supported by European Commission Framework 7 Project Grant. MSL received a scholarship from Science without Borders - CAPES. Funding of group Schmidt at the Netherlands Cancer Institute provided a partial grant and covered the IHC staining and image analysis. This work was also supported by grant UM1 CA164920 from the USA National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the USA Government or the BCFR. I.L. Andrulis holds the Anne and Max Tanenbaum Chair in Molecular Medicine at Mount Sinai Hospital of the Sinai Health System and the University of Toronto.
Publisher Copyright:
© 2018, © 2018 Taylor & Francis Group, LLC.
PY - 2018/12/2
Y1 - 2018/12/2
N2 - To better understand the expression pattern of programmed death-ligand 1 (PD-L1) expression in different breast cancer types, we characterized PD-L1 expression in tumor and tumor-infiltrating immune cells, in relation to mutation rate, BRCA1-like status and survival. We analyzed 410 primary treatment-naive breast tumors comprising 162 estrogen receptor-positive (ER+) and HER2−, 101 HER2+ and 147 triple-negative (TN) cancers. Pathologists quantified tumor-infiltrating lymphocytes (TILs) and PD-L1 expression in tumor cells and TILs using whole slides and tissue microarray. Mutation rate was assessed by DNA sequencing, BRCA1-like status using multiplex ligation-dependent probe amplification, and immune landscape by multiplex image analyses of CD4, CD68, CD8, FOXP3, cytokeratin, and PD-L1. Half of PD-L1 scores evaluated by tissue microarray were false negatives compared to whole slide evaluations. We observed at least 1% of PD-L1-positive (PD-L1+) cells in 53.1% of ER+HER2−, 73.3% of HER2+, and 84.4% of TN tumors. PD-L1 expression was higher in ductal compared to lobular carcinomas, also within ER+HER2− tumors (p = 0.04). High PD-L1+ TILs score (> 50%) was independently associated with better outcome in TN tumors (HR = 0.27; 95%CI = 0.10–0.69). Within TN tumors, PD-L1 and TIL scores showed a modest but significant positive association with the number of silent mutations, but no association with BRCA1-like status. Multiplex image analyses indicated that PD-L1 is expressed on multiple immune cells (CD68+ macrophages, CD4+, FOXP3+, and CD8+ T cells) in the breast tumor microenvironment, independent of the PD-L1 status of the tumor cells. We found no evidence that levels of PD-L1+ TILs in TN breast cancer are driven by high mutation rate or BRCA1-like status.
AB - To better understand the expression pattern of programmed death-ligand 1 (PD-L1) expression in different breast cancer types, we characterized PD-L1 expression in tumor and tumor-infiltrating immune cells, in relation to mutation rate, BRCA1-like status and survival. We analyzed 410 primary treatment-naive breast tumors comprising 162 estrogen receptor-positive (ER+) and HER2−, 101 HER2+ and 147 triple-negative (TN) cancers. Pathologists quantified tumor-infiltrating lymphocytes (TILs) and PD-L1 expression in tumor cells and TILs using whole slides and tissue microarray. Mutation rate was assessed by DNA sequencing, BRCA1-like status using multiplex ligation-dependent probe amplification, and immune landscape by multiplex image analyses of CD4, CD68, CD8, FOXP3, cytokeratin, and PD-L1. Half of PD-L1 scores evaluated by tissue microarray were false negatives compared to whole slide evaluations. We observed at least 1% of PD-L1-positive (PD-L1+) cells in 53.1% of ER+HER2−, 73.3% of HER2+, and 84.4% of TN tumors. PD-L1 expression was higher in ductal compared to lobular carcinomas, also within ER+HER2− tumors (p = 0.04). High PD-L1+ TILs score (> 50%) was independently associated with better outcome in TN tumors (HR = 0.27; 95%CI = 0.10–0.69). Within TN tumors, PD-L1 and TIL scores showed a modest but significant positive association with the number of silent mutations, but no association with BRCA1-like status. Multiplex image analyses indicated that PD-L1 is expressed on multiple immune cells (CD68+ macrophages, CD4+, FOXP3+, and CD8+ T cells) in the breast tumor microenvironment, independent of the PD-L1 status of the tumor cells. We found no evidence that levels of PD-L1+ TILs in TN breast cancer are driven by high mutation rate or BRCA1-like status.
KW - BRCA1-like
KW - Breast cancer
KW - PD-L1
KW - TILs
KW - mutations
UR - http://www.scopus.com/inward/record.url?scp=85053388119&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85053388119&partnerID=8YFLogxK
U2 - 10.1080/2162402X.2018.1509820
DO - 10.1080/2162402X.2018.1509820
M3 - Article
C2 - 30524905
AN - SCOPUS:85053388119
SN - 2162-4011
VL - 7
JO - OncoImmunology
JF - OncoImmunology
IS - 12
M1 - e1509820
ER -