Expression patterns of programmed death-ligand 1 in esophageal adenocarcinomas: comparison between primary tumors and metastases
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Expression analysis of programmed death-ligand 1 (PD-L1) may be helpful in guiding clinical decisions for immune checkpoint inhibition therapy, but testing by immunohistochemistry may be hampered by heterogeneous staining patterns within tumors and expression changes during metastatic course. PD-L1 expression (clone SP142) was investigated in esophageal adenocarcinomas using tissue microarrays (TMA) from 112 primary resected tumors, preoperative biopsies and full slide sections from a subset of these cases (n = 24), corresponding lymph node (n = 55) and distant metastases (n = 17). PD-L1 expression was scored as 0.1–1, >1, >5, >50% positive membranous staining of tumor cells and any positive staining of tumor-associated inflammatory infiltrates and/or stroma cells. There was a significant correlation with overall PD-L1 expression between the full slide sections and the TMA (p = 0.001), but not with the corresponding biopsies. PD-L1 expression in tumor cells >1% was detected in 8.0% of cases (9/112) and 51.8% of cases (58/112) in tumor-associated inflammatory infiltrates and/or stroma cells of primary tumors. Epithelial expression in metastases was found in 5.6% of cases (4/72) and immune cell expression in 18.1% of cases (13/72), but did not correlate with the expression pattern in the primary tumor. Overall PD-L1 expression in the primary tumor did not influence survival. However, PD-L1 expression was correlated with the number of CD3+ tumor-infiltrating lymphocytes in the tumor center, and a combinational score of PD-L1 status/CD3+ tumor-infiltrating lymphocytes was correlated with patients’ overall survival.
KeywordsPD-L1 Immunohistochemistry Esophageal adenocarcinoma Metastases
Programmed cell death protein 1
Programmed death-ligand 1
Tumor-associated inflammatory infiltrates and/or stroma cells
No particular funding source was used for this study.
B. Dislich and R. Langer performed the data analysis and wrote the paper. A. Stein, I. Zlobec and J. Galvan performed data analysis. C. A. Seiler, D. Kröll, S. Berezowska, J. Slotta-Huspenina and A. Walch contributed to data acquisition.
Compliance with ethical standards
Conflict of interest
R. Langer received advisory board honoraria from Bristol-Myers Squibb. S. Berezowska received advisory board honoraria from Merck Sharp & Dohme Corp. and consultation honoraria from Roche. There is no conflict of interest for the other authors of this study.
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