Journal
HISTOPATHOLOGY
Volume 73, Issue 3, Pages 397-406Publisher
WILEY
DOI: 10.1111/his.13528
Keywords
digital pathology; image analysis; immunotherapy; melanoma; oncology; pathology; PD-L1
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Funding
- Swiss National Science Foundation [P2SKP3_168322/2]
- FWF-Austrian Science Fund [P30325-B28]
- Edoardo R., Giovanni, Giuseppe and Chiarina Sassella foundation [16/10]
- Krebsliga beider Basel [KLbB-4182-03-2017]
- Swiss National Science Foundation (SNF) [P2SKP3_168322] Funding Source: Swiss National Science Foundation (SNF)
- Austrian Science Fund (FWF) [P30325] Funding Source: Austrian Science Fund (FWF)
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AimsImmune checkpoint inhibitors have become a successful treatment in metastatic melanoma. The high response rates in a subset of patients suggest that a sensitive companion diagnostic test is required. The predictive value of programmed death ligand 1 (PD-L1) staining in melanoma has been questioned due to inconsistent correlation with clinical outcome. Whether this is due to predictive irrelevance of PD-L1 expression or inaccurate assessment techniques remains unclear. The aim of this study was to develop a standardised digital protocol for the assessment of PD-L1 staining in melanoma and to compare the output data and reproducibility to conventional assessment by expert pathologists. Methods and resultsIn two cohorts with a total of 69 cutaneous melanomas, a highly significant correlation was found between pathologist-based consensus reading and automated PD-L1 analysis (r=0.97, P<0.0001). Digital scoring captured the full diagnostic spectrum of PD-L1 expression at single cell resolution. An average of 150472 melanoma cells (median 38668 cells; range=733-1078965) were scored per lesion. Machine learning was used to control for heterogeneity introduced by PD-L1-positive inflammatory cells in the tumour microenvironment. The PD-L1 image analysis protocol showed excellent reproducibility (r=1.0, P<0.0001) when carried out on independent workstations and reduced variability in PD-L1 scoring of human observers. When melanomas were grouped by PD-L1 expression status, we found a clear correlation of PD-L1 positivity with CD8-positive T cell infiltration, but not with tumour stage, metastasis or driver mutation status. ConclusionDigital evaluation of PD-L1 reduces scoring variability and may facilitate patient stratification in clinical practice.
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