• H E Danielsen, T S Hveem, E Domingo, M Pradhan, A Kleppe, R A Syvertsen, I Kostolomov, J A Nesheim, H A Askautrud, A Nesbakken, R A Lothe, A Svindland, N Shepherd, M Novelli, E Johnstone, I Tomlinson, R Kerr, and D J Kerr.
• Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway; Centre for Cancer Biomedicine, University of Oslo, Oslo, Norway; Nuffield Division of Clinical Laboratory Sciences, University of Oxford, Oxford, UK; Department of Informatics, University of Oslo, Oslo, Norway.
• Ann. Oncol. 2018 Mar 1; 29 (3): 616-623.

BackgroundWe report here the prognostic value of ploidy and digital tumour-stromal morphometric analyses using material from 2624 patients with early stage colorectal cancer (CRC).Patients And MethodsDNA content (ploidy) and stroma-tumour fraction were estimated using automated digital imaging systems and DNA was extracted from sections of formalin-fixed paraffin-embedded (FFPE) tissue for analysis of microsatellite instability. Samples were available from 1092 patients recruited to the QUASAR 2 trial and two large observational series (Gloucester, n = 954; Oslo University Hospital, n = 578). Resultant biomarkers were analysed for prognostic impact using 5-year cancer-specific survival (CSS) as the clinical end point.ResultsPloidy and stroma-tumour fraction were significantly prognostic in a multivariate model adjusted for age, adjuvant treatment, and pathological T-stage in stage II patients, and the combination of ploidy and stroma-tumour fraction was found to stratify these patients into three clinically useful groups; 5-year CSS 90% versus 83% versus 73% [hazard ratio (HR) = 1.77 (95% confidence interval (95% CI): 1.13-2.77) and HR = 2.95 (95% CI: 1.73-5.03), P < 0.001].ConclusionA novel biomarker, combining estimates of ploidy and stroma-tumour fraction, sampled from FFPE tissue, identifies stage II CRC patients with low, intermediate or high risk of CRC disease specific death, and can reliably stratify clinically relevant patient sub-populations with differential risks of tumour recurrence and may support choice of adjuvant therapy for these individuals.

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