Correlation of mismatch repair protein deficiency, PD-L1 and CD8 expression in high-grade urothelial carcinoma of the bladder Journal Article

Authors: Hodgson, A.; Vesprini, D.; Liu, S. K.; Xu, B.; Downes, M. R.
Article Title: Correlation of mismatch repair protein deficiency, PD-L1 and CD8 expression in high-grade urothelial carcinoma of the bladder
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. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.
Keywords: adult; protein expression; aged; aged, 80 and over; middle aged; retrospective studies; dna binding protein; major clinical study; dna-binding proteins; clinical feature; adjuvant therapy; antineoplastic agent; cd8 antigen; metabolism; protein depletion; inflammation; cohort analysis; pathology; retrospective study; tumor marker; physiology; mismatch repair; dna mismatch repair; cystectomy; urinary bladder; nephroureterectomy; carcinoma; protein deficiency; neoadjuvant chemotherapy; bladder carcinoma; transitional cell carcinoma; mismatch repair protein; immunopathology; mismatch repair protein pms2; bladder; programmed death 1 ligand 1; very elderly; humans; human; male; female; priority journal; article; biomarkers, tumor; cd274 protein, human; dna mismatch repair protein msh2; b7-h1 antigen; genitourinary pathology; cd8 antigens
Journal Title: Journal of Clinical Pathology
Volume: 73
Issue: 8
ISSN: 0021-9746
Publisher: BMJ Publishing Group Ltd.  
Date Published: 2020-08-01
Start Page: 519
End Page: 522
Language: English
DOI: 10.1136/jclinpath-2019-206256
PUBMED: 31919144
PROVIDER: scopus
Notes: Article -- Export Date: 1 October 2020 -- Source: Scopus
Citation Impact
MSK Authors
  1. Bin   Xu
    126 Xu