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Prognostic markers for colorectal cancer: estimating ploidy and stroma.
Danielsen, H E; Hveem, T S; Domingo, E; Pradhan, M; Kleppe, A; Syvertsen, R A; Kostolomov, I; Nesheim, J A; Askautrud, H A; Nesbakken, A; Lothe, R A; Svindland, A; Shepherd, N; Novelli, M; Johnstone, E; Tomlinson, I; Kerr, R; Kerr, D J.
Afiliação
  • Danielsen HE; 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.
  • Hveem TS; 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.
  • Domingo E; 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.
  • Pradhan M; Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway; Centre for Cancer Biomedicine, University of Oslo, Oslo, Norway.
  • Kleppe A; 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.
  • Syvertsen RA; Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway; Centre for Cancer Biomedicine, University of Oslo, Oslo, Norway.
  • Kostolomov I; Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway.
  • Nesheim JA; Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway; Centre for Cancer Biomedicine, University of Oslo, Oslo, Norway.
  • Askautrud HA; Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway; Centre for Cancer Biomedicine, University of Oslo, Oslo, Norway.
  • Nesbakken A; 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.
  • Lothe RA; 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, Facu
  • Svindland A; Institute of Clinical Medicine, University of Oslo, Oslo; Department of Pathology, Oslo University Hospital, Oslo, Norway.
  • Shepherd N; Gloucestershire Cellular Pathology Laboratory, Cheltenham General Hospital, Cheltenham.
  • Novelli M; Research Department of Pathology, University College London Medical School, London, UK.
  • Johnstone E; Department of Oncology, University of Oxford, Oxford, UK.
  • Tomlinson I; Molecular and Population Genetics Laboratory, University of Oxford, Oxford, UK.
  • Kerr R; Department of Oncology, University of Oxford, Oxford, UK.
  • Kerr DJ; Nuffield Division of Clinical Laboratory Sciences, University of Oxford, Oxford, UK. Electronic address: david.kerr@ndcls.ox.ac.uk.
Ann Oncol ; 29(3): 616-623, 2018 03 01.
Article em En | MEDLINE | ID: mdl-29293881
ABSTRACT

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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Colorretais Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Ann Oncol Assunto da revista: NEOPLASIAS Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Noruega
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Colorretais Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Ann Oncol Assunto da revista: NEOPLASIAS Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Noruega