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

Vargas, A. C.; Maclean, F. M.; Sioson, L.; Tran, D.; Bonar, F.; Mahar, A.; Cheah, A. L.; Russell, P.; Peter Grimison, P. G.; Louise Richardson, L. R.; Gill, A. J.

doi:10.1101/757625

bioRxiv · 10.1101/757625

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

Vargas, A. C.·Maclean, F. M.·Sioson, L.·Tran, D.·Bonar, F.·Mahar, A.·Cheah, A. L.·Russell, P.·Peter Grimison, P. G.·Louise Richardson, L. R.·Gill, A. J.

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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. Fishers 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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Vargas, A. C., Maclean, F. M., Sioson, L., Tran, D., Bonar, F., Mahar, A., Cheah, A. L., Russell, P., Peter Grimison, P. G., Louise Richardson, L. R., Gill, A. J.. 2019-09-04. PD-L1 expression in 522 selected sarcomas with subset analysis of recurrent or metastatic matched samples and association with tumour-infiltrating lymphocytes. https://doi.org/10.1101/757625

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