1. Somatic POLE proofreading domain mutation, immune response, and prognosis in colorectal cancer: a retrospective, pooled biomarker study 
Enric Domingo, PhD, Luke Freeman-Mills, BA, Emily Rayner, BSc, Mark Glaire, MBBS, Sarah Briggs, MBBS, Louis Vermeulen, MD, Evelyn Fessler, MSc, Prof Jan Paul Medema, PhD, Arnoud Boot, MSc, Prof Hans Morreau, PhD, Tom van Wezel, PhD, Gerrit-Jan Liefers, MD, Prof Ragnhild A Lothe, PhD, Stine A Danielsen, PhD, Anita Sveen, PhD, Prof Arild Nesbakken, MD, Prof Inti Zlobec, MD, Prof Alessandro Lugli, MD, Viktor H Koelzer, MD, Martin D Berger, MD, Sergi Castellví-Bel, PhD, Jenifer Muñoz, MSc, Marco de Bruyn, PhD, Prof Hans W Nijman, MD, Prof Marco Novelli, PhD, Kay Lawson, MBBS, Dahmane Oukrif, MSc, Eleni Frangou, MSc, Peter Dutton, MSc, Sabine Tejpar, MD, Mauro Delorenzi, PhD, Prof Rachel Kerr, MBBS, Prof David Kerr, MBChB, Prof Ian Tomlinson, PhD, Dr David N Church, DPhil 
The Lancet Gastroenterology & Hepatology 
Volume 1, Issue 3, Pages (November 2016)
DOI: /S (16)
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2. Figure 1
Study schema
All informative cases were used for analyses. Pathological and molecular analyses exclude patients in whom POLE screening was unsuccessful, and three cases with mutations of uncertain pathogenicity (appendix p 12). Analyses of clinical outcome were limited to patients with stage II/III disease, who underwent complete tumour resection and, in the case of the non-trial cohorts, were alive ≥30 days following diagnosis. Multivariable analyses were limited to patients for whom complete data for all covariables used in Cox proportional hazards models were available. MMR=mismatch repair. RFI=recurrence-free interval. DFS=disease-free survival. *See appendix p 12. †Applies only to cases in the non-trial cohorts.
The Lancet Gastroenterology & Hepatology 2016 1, DOI: ( /S (16) )
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3. Figure 2
Immune response according to tumour POLE proofreading domain mutation and mismatch repair status
(A) Quantification of CD8 immunohistochemistry for POLE wild-type, mismatch repair proficient colorectal cancers (MMR-P; n=20), POLE wild-type, mismatch repair deficient colorectal cancers (MMR-D; n=13), and POLE proofreading domain mutant (POLE; n=18) colorectal cancers. (B) Expression of cytotoxic T-cell markers, effector cytokines, and immune checkpoints in MMR-P (n=452), MMR-D (n=78), and POLE (n=13) TCGA colorectal cancers. Horizontal lines and bars represent the median and interquartile range (IQR), respectively. Statistical comparison between groups was made by unadjusted two-sided Mann-Whitney test. *p<0·01. †p<0·001. ‡p<0·05.
The Lancet Gastroenterology & Hepatology 2016 1, DOI: ( /S (16) )
Copyright © 2016 Elsevier Ltd Terms and Conditions

4. Figure 3
Clinical outcome of stage II/III colorectal cancers according to tumour POLE proofreading domain mutation and mismatch repair status
Kaplan-Meier curves showing colorectal cancer recurrence (A), disease-free survival (B), and overall survival (C) of POLE wild-type, mismatch repair proficient (MMR-P); POLE wild-type, mismatch repair deficient (MMR-D); and POLE proofreading domain-mutant (POLE) colorectal cancers in pooled analyses. p values indicate comparison between POLE and MMR-P tumours by unadjusted log-rank test.
The Lancet Gastroenterology & Hepatology 2016 1, DOI: ( /S (16) )
Copyright © 2016 Elsevier Ltd Terms and Conditions

5. Figure 4
Colorectal cancer recurrence according to tumour POLE proofreading domain mutation and mismatch repair status by disease stage
Kaplan-Meier curves showing cumulative probability of recurrence of POLE wild-type, mismatch repair proficient (MMR-P); POLE wild-type, mismatch repair deficient (MMR-D); and POLE proofreading domain-mutant (POLE) stage II (A) and stage III (B) colorectal cancers. p values indicate comparison between POLE and MMR-P tumours by unadjusted log-rank test.
The Lancet Gastroenterology & Hepatology 2016 1, DOI: ( /S (16) )
Copyright © 2016 Elsevier Ltd Terms and Conditions