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PD-L1 expression in 522 selected sarcomas with subset analysis of recurrent or metastatic matched samples and association with tumour-infiltrating lymphocytes

View ORCID ProfileAna Cristina Vargas, Fiona M Maclean, Loretta Sioson, Dinh Tran, Fiona Bonar, Annabelle Mahar, Alison L. Cheah, Peter Russell, Peter Grimison, Louise Richardson, Anthony J Gill
doi: https://doi.org/10.1101/757625
Ana Cristina Vargas
1Department of Anatomical Pathology, Douglass Hanly Moir Pathology, Macquarie Park NSW 2113 Australia
2Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards NSW 2065 Australia
3University of Sydney, Sydney NSW 2006 Australia
4School of Medicine, Notre Dame University, Sydney NSW 2007 Australia
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  • ORCID record for Ana Cristina Vargas
  • For correspondence: cvargas@dhm.com.au
Fiona M Maclean
1Department of Anatomical Pathology, Douglass Hanly Moir Pathology, Macquarie Park NSW 2113 Australia
2Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards NSW 2065 Australia
5Department of Clinical Medicine, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia
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Loretta Sioson
2Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards NSW 2065 Australia
3University of Sydney, Sydney NSW 2006 Australia
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Dinh Tran
1Department of Anatomical Pathology, Douglass Hanly Moir Pathology, Macquarie Park NSW 2113 Australia
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Fiona Bonar
1Department of Anatomical Pathology, Douglass Hanly Moir Pathology, Macquarie Park NSW 2113 Australia
4School of Medicine, Notre Dame University, Sydney NSW 2007 Australia
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Annabelle Mahar
6Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown NSW 2050 Australia
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Alison L. Cheah
1Department of Anatomical Pathology, Douglass Hanly Moir Pathology, Macquarie Park NSW 2113 Australia
4School of Medicine, Notre Dame University, Sydney NSW 2007 Australia
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Peter Russell
1Department of Anatomical Pathology, Douglass Hanly Moir Pathology, Macquarie Park NSW 2113 Australia
3University of Sydney, Sydney NSW 2006 Australia
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Peter Grimison
3University of Sydney, Sydney NSW 2006 Australia
7Department Of Medical Oncology, Chris O’Brien Lifehouse
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Louise Richardson
1Department of Anatomical Pathology, Douglass Hanly Moir Pathology, Macquarie Park NSW 2113 Australia
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Anthony J Gill
2Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards NSW 2065 Australia
3University of Sydney, Sydney NSW 2006 Australia
8NSW Health Pathology, Department of Anatomical Pathology, Royal North Shore Hospital, Sydney NSW 2065 Australia
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Abstract

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 <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.

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Posted September 04, 2019.
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PD-L1 expression in 522 selected sarcomas with subset analysis of recurrent or metastatic matched samples and association with tumour-infiltrating lymphocytes
Ana Cristina Vargas, Fiona M Maclean, Loretta Sioson, Dinh Tran, Fiona Bonar, Annabelle Mahar, Alison L. Cheah, Peter Russell, Peter Grimison, Louise Richardson, Anthony J Gill
bioRxiv 757625; doi: https://doi.org/10.1101/757625
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PD-L1 expression in 522 selected sarcomas with subset analysis of recurrent or metastatic matched samples and association with tumour-infiltrating lymphocytes
Ana Cristina Vargas, Fiona M Maclean, Loretta Sioson, Dinh Tran, Fiona Bonar, Annabelle Mahar, Alison L. Cheah, Peter Russell, Peter Grimison, Louise Richardson, Anthony J Gill
bioRxiv 757625; doi: https://doi.org/10.1101/757625

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