Prevalence of PD-L1 expression in matched recurrent and/or metastatic sarcoma samples and in a range of selected sarcomas subtypes

We assessed the frequency of programmed death-ligand 1 (PD-L1) expression by immunohistochemistry (IHC) in a cohort of 522 sarcomas from 457 patients, incuding a subset of 46 patients with 63 matched samples from local recurrence or metastases with primary tumours and/or metachronous metastases. We...

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Veröffentlicht in:PloS one 2020-04, Vol.15 (4), p.e0222551-e0222551
Hauptverfasser: Vargas, Ana Cristina, Maclean, Fiona M, Sioson, Loretta, Tran, Dinh, Bonar, Fiona, Mahar, Annabelle, Cheah, Alison L, Russell, Peter, Grimison, Peter, Richardson, Louise, Gill, Anthony J
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container_title PloS one
container_volume 15
creator Vargas, Ana Cristina
Maclean, Fiona M
Sioson, Loretta
Tran, Dinh
Bonar, Fiona
Mahar, Annabelle
Cheah, Alison L
Russell, Peter
Grimison, Peter
Richardson, Louise
Gill, Anthony J
description We assessed the frequency of programmed death-ligand 1 (PD-L1) expression by immunohistochemistry (IHC) in a cohort of 522 sarcomas from 457 patients, incuding a subset of 46 patients with 63 matched samples from local recurrence or metastases with primary tumours and/or metachronous metastases. We also investigated the correlation of PD-L1 with the presence and degree of tumour-infiltrating lymphocytes (TILs) in a subset of cases. IHC was performed using the PD-L1 SP263 companion kit (VENTANA) on tissue microarrays from an archival cohort. Evaluation of PD-L1 and TILs was performed on full sections for a subset of 23 cases. Fisher's exact and Mann Whitney test were used to establish significance (P
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We also investigated the correlation of PD-L1 with the presence and degree of tumour-infiltrating lymphocytes (TILs) in a subset of cases. IHC was performed using the PD-L1 SP263 companion kit (VENTANA) on tissue microarrays from an archival cohort. Evaluation of PD-L1 and TILs was performed on full sections for a subset of 23 cases. Fisher's exact and Mann Whitney test were used to establish significance (P &lt;0.05). PD-L1 positive expression (≥1%) was identified in 31% of undifferentiated pleomorphic sarcomas, 29% of angiosarcomas, 26% of rhabdomyosarcomas, 18% of myxofibrosarcomas, 11% of leiomyosarcomas and 10% of dedifferentiated liposarcomas. Negative expression was present in all atypical lipomatous tumous/well-differentiated lipoasarcomas, myxoid liposarcomas, synovial sarcomas, pleomorphic liposarcomas, and Ewing sarcomas. PD-L1 IHC was concordant in 81% (38 of 47) of matched/paired samples. PD-L1 IHC was discordant in 19% (9 of 47 matched/paired samples), displaying differences in the proportion of cells expressing PD-L1 amongst paired samples with the percentage of PD-L1-positive cells increasing in the metastatic/recurrent site compared to the primary in 6 of 9 cases (67%). Significant correlation between PD-L1 expression and the degree of TILs was exclusively identified in the general cohort of leiomyosarcomas, but not in other sarcoma subtypes or in metastatic/recurrent samples. We conclude that the prevalence of PD-L1 expression in selected sarcomas is variable and likely to be clone dependent. Importantly, we demonstrated that PD-L1 can objectively increase in a small proportion of metastases/recurrent sarcomas, offering the potential of treatment benefit to immune checkpoint inhibitors in this metastatic setting.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0222551</identifier><identifier>PMID: 32294103</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Apoptosis ; Biology and Life Sciences ; Breast cancer ; Cloning ; Correlation ; Ewings sarcoma ; Hospitals ; Immune checkpoint inhibitors ; Immunohistochemistry ; Laboratories ; Ligands ; Lymphocytes ; Medical diagnosis ; Medical research ; Medicine ; Medicine and Health Sciences ; Metastases ; Metastasis ; Pathology ; PD-L1 protein ; Research and Analysis Methods ; Sarcoma ; Statistical analysis ; Tumors</subject><ispartof>PloS one, 2020-04, Vol.15 (4), p.e0222551-e0222551</ispartof><rights>2020 Vargas et al. 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We also investigated the correlation of PD-L1 with the presence and degree of tumour-infiltrating lymphocytes (TILs) in a subset of cases. IHC was performed using the PD-L1 SP263 companion kit (VENTANA) on tissue microarrays from an archival cohort. Evaluation of PD-L1 and TILs was performed on full sections for a subset of 23 cases. Fisher's exact and Mann Whitney test were used to establish significance (P &lt;0.05). PD-L1 positive expression (≥1%) was identified in 31% of undifferentiated pleomorphic sarcomas, 29% of angiosarcomas, 26% of rhabdomyosarcomas, 18% of myxofibrosarcomas, 11% of leiomyosarcomas and 10% of dedifferentiated liposarcomas. Negative expression was present in all atypical lipomatous tumous/well-differentiated lipoasarcomas, myxoid liposarcomas, synovial sarcomas, pleomorphic liposarcomas, and Ewing sarcomas. PD-L1 IHC was concordant in 81% (38 of 47) of matched/paired samples. PD-L1 IHC was discordant in 19% (9 of 47 matched/paired samples), displaying differences in the proportion of cells expressing PD-L1 amongst paired samples with the percentage of PD-L1-positive cells increasing in the metastatic/recurrent site compared to the primary in 6 of 9 cases (67%). Significant correlation between PD-L1 expression and the degree of TILs was exclusively identified in the general cohort of leiomyosarcomas, but not in other sarcoma subtypes or in metastatic/recurrent samples. We conclude that the prevalence of PD-L1 expression in selected sarcomas is variable and likely to be clone dependent. Importantly, we demonstrated that PD-L1 can objectively increase in a small proportion of metastases/recurrent sarcomas, offering the potential of treatment benefit to immune checkpoint inhibitors in this metastatic setting.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>32294103</pmid><doi>10.1371/journal.pone.0222551</doi><orcidid>https://orcid.org/0000-0003-3798-5088</orcidid><oa>free_for_read</oa></addata></record>
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subjects Apoptosis
Biology and Life Sciences
Breast cancer
Cloning
Correlation
Ewings sarcoma
Hospitals
Immune checkpoint inhibitors
Immunohistochemistry
Laboratories
Ligands
Lymphocytes
Medical diagnosis
Medical research
Medicine
Medicine and Health Sciences
Metastases
Metastasis
Pathology
PD-L1 protein
Research and Analysis Methods
Sarcoma
Statistical analysis
Tumors
title Prevalence of PD-L1 expression in matched recurrent and/or metastatic sarcoma samples and in a range of selected sarcomas subtypes
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