p53 immunohistochemistry in high‐grade urothelial carcinoma of the bladder is prognostically significant

Hodgson, Anjelica; Xu, Bin; Downes, Michelle

doi:10.1111/his.13225

Cited by 47 publications

(50 citation statements)

References 38 publications

(107 reference statements)

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“…Triplicate core TMAs were constructed from 201 of the available 235 cases. Technical details regarding construction of the TMAs have been previously described 12. A H&E section was examined from each TMA block to confirm tumour adequacy.…”

Section: Methodsmentioning

confidence: 99%

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

Hodgson¹,

Vesprini

Liu

et al. 2020

J Clin Pathol

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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.

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Section: Methodsmentioning

confidence: 99%

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

Hodgson¹,

Vesprini

Liu

et al. 2020

J Clin Pathol

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“…Triplicate 1‐mm core TMAs were constructed using a TMA instrument (Beecher Instruments, Silver Springs, MD, USA), as previously described . Sections from the TMA blocks were stained with haematoxylin and eosin (H&E) to confirm the adequacy of tumour sampling and to facilitate orientation during the interpretation of the PD‐L1 staining.…”

Section: Methodsmentioning

confidence: 99%

Inter‐ and intraobserver agreement of programmed death ligand 1 scoring in head and neck squamous cell carcinoma, urothelial carcinoma and breast carcinoma

et al. 2019

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Aims Programmed death‐ligand 1 (PD‐L1) expression by tumour cells (TC) is a mechanism for tumour immune escape through down‐regulation of antitumour T cell responses and is a target for immunotherapy. PD‐L1 status as a predictor of treatment response has led to the development of multiple biomarkers with different reference cut‐offs. We assessed pathologist consistency in evaluating PD‐L1 immunopositivity by examining the inter‐ and intraobserver agreement using various antibody clones and different cancer types. Methods and results PD‐L1 expression in TC and immune cells (IC) was manually scored in 27 head and neck squamous cell carcinoma (HSCC), 30 urothelial carcinoma (UC) and breast carcinoma (BC) using three commercial clones (SP263, SP142, 22C3) and one platform‐independent test (E1L3N). For interobserver agreement, PD‐L1 status was evaluated blindly by three pathologists. For intraobserver agreement, PD‐L1 expression was re‐evaluated following a wash‐out period. Intraclass correlation coefficient (ICC), overall percentage agreement (OPA) and κ‐values were calculated. Using clinical algorithms, the percentage of PD‐L1‐positive cases in HSCC, BC and UC were 15–81%, 47–67% and 7–43%, respectively. The percentage of PD‐L1 positive cases relied heavily on the algorithm/cut‐off values used. Almost perfect interobserver agreement was achieved using SP263 and E1L3N in HSCC, 22C3, SP142 and E1L3N in BC and 22C3 in UC. The SP142 clone in UC and HSCC showed moderate agreement and was associated with lower ICC and decreased intraobserver concordance. Conclusions Excellent inter‐ and intraobserver agreement can be achieved using SP263, 22C3 and E1L3N, whereas PD‐L1 scoring using SP142 clone is associated with a higher level of subjectivity.

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“…Triplicate‐core TMAs were created as previously described . In brief, three independent sites containing tumour were circled on a single representative slide from each case.…”

Section: Methodsmentioning

confidence: 99%

“…Triplicate-core TMAs were created as previously described. 29 In brief, three independent sites containing tumour were circled on a single representative slide from each case. Triplicate 1-mm-core TMAs were constructed with a TMA instrument (Beecher Instruments, Silver Springs, MD, USA) used to punch the areas of interest from the respective tumour blocks.…”

Section: T I S S U E M I C R O a R R A Y ( T M A ) C O N S T R U C T mentioning

confidence: 99%

Basal‐subtype bladder tumours show a ‘hot’ immunophenotype

et al. 2018

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p53 immunohistochemistry in high‐grade urothelial carcinoma of the bladder is prognostically significant

Abstract: Prior to this study, the p53 null phenotype was not well described in urothelial carcinoma of the bladder. Abnormal p53 immunoexpression (null staining pattern or staining in >50% of cells) is prognostic in terms of oncological outcome.

Cited by 47 publications

References 38 publications

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

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

Inter‐ and intraobserver agreement of programmed death ligand 1 scoring in head and neck squamous cell carcinoma, urothelial carcinoma and breast carcinoma

Basal‐subtype bladder tumours show a ‘hot’ immunophenotype

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