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Correlation of mismatch repair protein deficiency, PD-L1 and CD8 expression in high-grade urothelial carcinoma of the bladder
  1. Anjelica Hodgson1,2,
  2. Danny Vesprini3,
  3. Stanley K Liu3,
  4. Bin Xu4,
  5. Michelle R Downes1,2
  1. 1 Laboratory Medicine and Molecular Diagnostics, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
  2. 2 Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
  3. 3 Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
  4. 4 Pathology, Memorial Sloan Kettering Cancer Center, New York City, New York, USA
  1. Correspondence to Dr Michelle R Downes, Laboratory Medicine and Molecular Diagnostics, Sunnybrook Health Sciences Centre, Toronto, M4N 3M5, Canada; michelle.downes{at}sunnybrook.ca

Abstract

Mismatch repair-deficient (d-MMR) tumours have been reported to show susceptibility to immune checkpoint inhibitors targeting programmed death-1/PD ligand-1 (PD-1/PD-L1). In this study, we sought to correlate the association of d-MMR, PD-L1 and CD8 expression in muscle invasive, high-grade urothelial carcinoma (HGUC) of bladder. A tissue microarray (TMA) was constructed from 201 cases and sequentially stained with PD-L1, CD8, MSH2, MSH6, MLH1 and PMS2. PD-L1 was assessed in tumour and immune cells. CD8 was assessed in a hotspot fashion with results averaged across cores. Loss of nuclear MMR expression on TMA sections was further assessed using corresponding whole tissue sections. d-MMR was identified in four cases (2%). The mean CD8 count was significantly higher in d-MMR tumours (10 vs 35, p=0.007) as was the proportion of PD-L1 positivity (75% vs 20%, p=0.031). d-MMR is uncommon in HGUC of bladder but shows strong correlation with cytotoxic T lymphocyte infiltration and PD-L1 tissue expression.

  • bladder
  • carcinoma
  • genitourinary pathology
  • immunopathology
  • inflammation
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Footnotes

  • Handling editor Cheok Soon Lee.

  • Presented at This work was presented in part at the 2019 European Congress of Pathology, 8 September 2019, Nice, France.

  • Contributors All authors were a part of the conception and design of the study. AH, BX and MRD gathered and interpreted the data. All authors contributed to the drafting and editing of the manuscript. All authors approved the final version of the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval Approval for this research was obtained from the research ethics board of Sunnybrook Health Sciences Centre (REB 187–2016).

  • Provenance and peer review Not commissioned; externally peer reviewed.

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