title: Expression patterns of programmed death-ligand 1 in esophageal adenocarcinomas: comparison between primary tumors and metastases.
abstract: 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.
authors.affiliation: Institute of Pathology, University of Bern, Murtenstr. 31, 3010, Bern, Switzerland.
authors.forename: Bastian
authors.initials: B
authors.lastname: Dislich
authors.affiliation: Institute of Pathology, University of Bern, Murtenstr. 31, 3010, Bern, Switzerland.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Stein
authors.affiliation: Department of Visceral Surgery and Medicine, Inselspital University Hospital Bern, University Bern, 3010, Bern, Switzerland.
authors.forename: Christian A
authors.initials: CA
authors.lastname: Seiler
authors.affiliation: Department of Visceral Surgery and Medicine, Inselspital University Hospital Bern, University Bern, 3010, Bern, Switzerland.
authors.forename: Dino
authors.initials: D
authors.lastname: Kröll
authors.affiliation: Institute of Pathology, University of Bern, Murtenstr. 31, 3010, Bern, Switzerland.
authors.forename: Sabina
authors.initials: S
authors.lastname: Berezowska
authors.affiliation: Institute of Pathology, University of Bern, Murtenstr. 31, 3010, Bern, Switzerland.
authors.forename: Inti
authors.initials: I
authors.lastname: Zlobec
authors.affiliation: Institute of Pathology, University of Bern, Murtenstr. 31, 3010, Bern, Switzerland.
authors.forename: José
authors.initials: J
authors.lastname: Galvan
authors.affiliation: Institute of Pathology, Technical University of Munich, 81675, Munich, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Slotta-Huspenina
authors.affiliation: Research Unit Analytical Pathology, Helmholtz Center Munich, German Research Center for Environmental Health, 85764, Oberschleißheim, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Walch
authors.affiliation: Institute of Pathology, University of Bern, Murtenstr. 31, 3010, Bern, Switzerland. rupert.langer@pathology.unibe.ch.
authors.forename: Rupert
authors.initials: R
authors.lastname: Langer
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000556:secondary / Q000601:surgery; D060890:B7-H1 Antigen / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D059016:Tumor Microenvironment
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human
keywords: Esophageal adenocarcinoma; Immunohistochemistry; Metastases; PD-L1