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 |
DOI/URL: | |
Notes: | Article -- Export Date: 1 October 2020 -- Source: Scopus |