Prognostic markers for colorectal cancer: estimating ploidy and stroma.,Annals of Oncology

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Prognostic markers for colorectal cancer: estimating ploidy and stroma.
Annals of Oncology ( IF 56.7 ) Pub Date : 2018-03-01 , DOI: 10.1093/annonc/mdx794
H E Danielsen ₁ , T S Hveem ₂ , E Domingo ₃ , M Pradhan ₄ , A Kleppe ₂ , R A Syvertsen ₄ , I Kostolomov ₅ , J A Nesheim ₄ , H A Askautrud ₄ , A Nesbakken ₆ , R A Lothe ₇ , A Svindland ₈ , N Shepherd ₉ , M Novelli ₁₀ , E Johnstone ₁₁ , I Tomlinson ₁₂ , R Kerr ₁₁ , D J Kerr ₁₃

Affiliation

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.
Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway; Centre for Cancer Biomedicine, University of Oslo, Oslo, Norway; Department of Informatics, University of Oslo, Oslo, Norway.
Department of Oncology, University of Oxford, Oxford, UK; Molecular and Population Genetics Laboratory, University of Oxford, Oxford, UK; Oxford NIHR Comprehensive Biomedical Research Centre, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway; Centre for Cancer Biomedicine, University of Oslo, Oslo, Norway.
Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway.
Centre for Cancer Biomedicine, University of Oslo, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo; Department of Gastrointestinal Surgery, Oslo University Hospital, Oslo; K.G. Jebsen Colorectal Cancer Research Centre, Oslo University Hospital, Oslo.
Centre for Cancer Biomedicine, University of Oslo, Oslo, Norway; K.G. Jebsen Colorectal Cancer Research Centre, Oslo University Hospital, Oslo; Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital - Norwegian Radium Hospital, Oslo; Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo.
Institute of Clinical Medicine, University of Oslo, Oslo; Department of Pathology, Oslo University Hospital, Oslo, Norway.
Gloucestershire Cellular Pathology Laboratory, Cheltenham General Hospital, Cheltenham.
Research Department of Pathology, University College London Medical School, London, UK.
Department of Oncology, University of Oxford, Oxford, UK.
Molecular and Population Genetics Laboratory, University of Oxford, Oxford, UK.
Nuffield Division of Clinical Laboratory Sciences, University of Oxford, Oxford, UK.

Background We 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 methods DNA 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. Results Ploidy 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]. Conclusion A 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.

中文翻译：

结直肠癌的预后标志物：估计倍性和基质。

背景我们在此报告了倍性和数字肿瘤基质形态测量分析的预后价值，使用的材料来自 2624 名早期结直肠癌 (CRC) 患者。患者和方法使用自动数字成像系统估计 DNA 含量（倍性）和基质肿瘤分数，并从福尔马林固定石蜡包埋 (FFPE) 组织切片中提取 DNA，用于分析微卫星不稳定性。样本来自 QUASAR 2 试验和两个大型观察系列招募的 1092 名患者（格洛斯特，n = 954；奥斯陆大学医院，n = 578）。使用 5 年癌症特异性生存 (CSS) 作为临床终点，分析所得生物标志物的预后影响。结果在调整了 II 期患者年龄、辅助治疗和病理 T 分期的多变量模型中，倍性和基质肿瘤分数具有显着的预后作用，并且发现倍性和基质肿瘤分数的组合将这些患者分为三类临床有用的团体； 5 年 CSS 90% 与 83% 与 73% [风险比 (HR) = 1.77（95% 置信区间 (95% CI)：1.13-2.77）和 HR = 2.95（95% CI：1.73-5.03），P < 0.001]。结论一种新型生物标志物，结合从 FFPE 组织中取样的倍性和基质肿瘤分数的估计，可以识别具有低、中或高 CRC 疾病特异性死亡风险的 II 期 CRC 患者，并且可以可靠地对具有差异性的临床相关患者亚群进行分层。肿瘤复发的风险，可能支持这些个体选择辅助治疗。

更新日期：2017-12-27

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