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Tumour cell budding and spread through air spaces in squamous cell carcinoma of the lung – Determination and validation of ... 1 1 Introduction 2 2 Materials and methods 2 2.1 TCGA cohort 2 2.2 Validation cohort 2 2.3 Analysis of digitalized slides 2 2.4 Histopathologic analysis 2 2.5 Tumour cell budding 2 2.6 Minimal cell nest size (MCNS) 2 2.7 Established budding-based previous grading approaches 4 2.8 Spread through air spaces (STAS) 4 2.9 Immune cell infiltration 4 2.10 Stromal content 4 2.11 Statistical analyses 4 3 Results 4 3.1 Dispersion of the parameters 4 3.2 Cut-off identification-TCGA cohort 4 3.3 Clinicopathologic correlations 6 3.4 Correlation 1 HPF – 10 HPF 6 3.5 Univariate survival analyses (10 HPF) 6 3.6 Multivariate survival analyses (10 HPF) 7 3.7 Uni- and multivariate survival analyses (1 HPF) 8 3.8 Validation 8 3.9 Interobserver agreement 8 4 Discussion 8 5 Conclusion 10 6 Disclosure 10 CRediT authorship contribution statement 10 Declaration of Competing Interest 10 Acknowledgements 10 Appendix A Supplementary data 10 References 11

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UND

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nonfiction