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Correlation of PD-L1 expression with immunohistochemically determined molecular profile in endometrial carcinomas

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Abstract

Endometrial carcinoma programmed death-ligand 1 (PD-L1) expression in tumor cells (TCs) and tumor-associated inflammatory cells (ICs) have recently been reported in several studies which vary in terms of their cohort size, design, and methodology. We aimed to assess PD-L1 staining in endometrial carcinomas and correlate this with clinical and pathological factors and PTEN, ARID1A, p53, and MMR protein expression. PD-L1 immunohistochemistry was performed on whole tissue sections of all tumor blocks of 59 consecutive unselected endometrial carcinomas between November 2018 and September 2019. TC and IC PD-L1 positivity with a 1% cut-off value was observed in 10.2% and 67.8% of cases, respectively, and with a 5% cut-off value in 3.4% and 42.4% of cases, respectively. TC PD-L1 positivity with both 1% and 5% cut-off values was significantly related to ARID1A loss (p = 0.001 and p = 0.046, respectively). IC PD-L1 positivity with 1% and 5% cut-off values and combined score were significantly associated with MMR protein deficiency (p = 0.041, p = 0.031, and p = 0.028, respectively). Advanced stage tumors exhibited more frequent PD-L1 expression in ICs (p = 0.039). MELF-type myometrial invasion pattern was more common in tumors with ARID1A loss (p = 0.047). We observed higher rates of IC PD-L1 positivity in endometrial carcinomas than documented in prior studies; this may be related to our usage of “recent” paraffin blocks and whole tissue sections of all tumor blocks. There was a much higher PD-L1 expression in the ICs compared to TCs in our cases. We confirm a previously documented association between MMR deficiency and PD-L1 expression and show a novel association between ARID1A loss and PD-L1 expression in endometrial carcinomas. ARID1A loss represents a potential biomarker of immune checkpoint inhibitor response in endometrial carcinoma.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This study was supported by Istanbul Medeniyet University Scientific Research Project fund.

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Authors and Affiliations

  1. Department of Pathology, Istanbul Medeniyet University Goztepe Training and Research Hospital, Dr. Erkin Caddesi, Göztepe Egt. ve Aras. Hastanesi Patoloji Laboratuarı 34720 Kadıköy, Istanbul, Turkey

    Gozde Kir, Tuce Soylemez, Zeynep Cagla Olgun & Abdullah Aydin

  2. Department of Pathology, Belfast Health and Social Care Trust, Grosvenor Road, Belfast, BT9 7AB, UK

    W. Glenn McCluggage

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  1. Gozde Kir
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Contributions

G.K.: Designed the research study, contributed essential reagents or tools, performed the research, reviewed and corrected the manuscript.

T.S., Z.C.O.: Analyzed the data, wrote the paper.

A.A.: Contributed essential reagents or tools, performed the research.

W.G.M.: Reviewed and corrected the manuscript.

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Correspondence to Gozde Kir.

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Kir, G., Soylemez, T., Olgun, Z.C. et al. Correlation of PD-L1 expression with immunohistochemically determined molecular profile in endometrial carcinomas. Virchows Arch 477, 845–856 (2020). https://doi.org/10.1007/s00428-020-02867-9

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