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

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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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 (2020). https://doi.org/10.1007/s00428-020-02867-9

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Keywords

  • Endometrial carcinoma
  • Immunohistochemistry
  • MMR
  • ARID1A
  • PTEN
  • PD-L1