Prognostic impact of genomic instability in colorectal cancer

T S Hveem; M A Merok; M E Pretorius; M Novelli; M S Bævre; O H Sjo; N Clinch; K Liestøl; A Svindland; R A Lothe; A Nesbakken; H E Danielsen

doi:10.1038/bjc.2014.133

Prognostic impact of genomic instability in colorectal cancer

Br J Cancer. 2014 Apr 15;110(8):2159-64. doi: 10.1038/bjc.2014.133. Epub 2014 Mar 18.

Authors

T S Hveem¹, M A Merok², M E Pretorius³, M Novelli⁴, M S Bævre³, O H Sjo⁵, N Clinch⁶, K Liestøl⁷, A Svindland⁸, R A Lothe², A Nesbakken⁹, H E Danielsen¹⁰

Affiliations

¹ 1] Institute for Cancer Genetics and Informatics, Oslo University Hospital, PO Box 4950 Nydalen, 0424 Oslo, Norway [2] Centre for Cancer Biomedicine, University of Oslo, PO Box 4950 Nydalen, 0424 Oslo, Norway [3] Department of Informatics, University of Oslo, PO Box 1080 Blindern, 0316 Oslo, Norway.
² 1] Centre for Cancer Biomedicine, University of Oslo, PO Box 4950 Nydalen, 0424 Oslo, Norway [2] Department of Cancer Prevention, Institute for Cancer Research, Oslo University Hospital, PO Box 4953 Nydalen, 0424 Oslo, Norway [3] Institute of Clinical Medicine, University of Oslo, PO Box 1171 Blindern, 0318 Oslo, Norway.
³ 1] Institute for Cancer Genetics and Informatics, Oslo University Hospital, PO Box 4950 Nydalen, 0424 Oslo, Norway [2] Centre for Cancer Biomedicine, University of Oslo, PO Box 4950 Nydalen, 0424 Oslo, Norway.
⁴ 1] Centre for Cancer Biomedicine, University of Oslo, PO Box 4950 Nydalen, 0424 Oslo, Norway [2] Department of Pathology, University College Hospital, London WC1E 6JJ, UK.
⁵ Department of Gastrointestinal Surgery, Oslo University Hospital, PO Box 4950 Nydalen, 0424 Oslo, Norway.
⁶ Institute for Cancer Genetics and Informatics, Oslo University Hospital, PO Box 4950 Nydalen, 0424 Oslo, Norway.
⁷ 1] Centre for Cancer Biomedicine, University of Oslo, PO Box 4950 Nydalen, 0424 Oslo, Norway [2] Department of Informatics, University of Oslo, PO Box 1080 Blindern, 0316 Oslo, Norway.
⁸ 1] Institute of Clinical Medicine, University of Oslo, PO Box 1171 Blindern, 0318 Oslo, Norway [2] Department of Pathology, Oslo University Hospital, PO Box 4950 Nydalen, 0424 Oslo, Norway.
⁹ 1] Centre for Cancer Biomedicine, University of Oslo, PO Box 4950 Nydalen, 0424 Oslo, Norway [2] Institute of Clinical Medicine, University of Oslo, PO Box 1171 Blindern, 0318 Oslo, Norway [3] Department of Gastrointestinal Surgery, Oslo University Hospital, PO Box 4950 Nydalen, 0424 Oslo, Norway.
¹⁰ 1] Institute for Cancer Genetics and Informatics, Oslo University Hospital, PO Box 4950 Nydalen, 0424 Oslo, Norway [2] Centre for Cancer Biomedicine, University of Oslo, PO Box 4950 Nydalen, 0424 Oslo, Norway [3] Department of Informatics, University of Oslo, PO Box 1080 Blindern, 0316 Oslo, Norway [4] Nuffield Division of Clinical Laboratory Sciences, University of Oxford, Oxford, UK.

Abstract

Background: The prognostic impact of an indication of chromosomal instability (CIN) is evaluated in a consecutive series of 952 colorectal cancer patients treated at Aker University Hospital, Norway, during 1993-2003. Microsatellite instability (MSI) in this case series has recently been reported and made it possible to find the co-occurrence and compare the prognostic significance of CIN and MSI.

Methods: Data sets for overall survival (OS; n=855) and time to recurrence (TTR; n=579) were studied. To reveal CIN we used automated image cytometry (ICM). Non-diploid histograms were taken as indicative of the presence of CIN. PCR-based measures of MSI in this material have already been described.

Results: As with MSI, CIN was found to be an independent predictor of early relapse and death among stage II patients (TTR: n=278: HR 2.19 (95% CI: 1.35-3.55), P=0.002). Of the MSI tumours (16%), 71% were found to be DNA diploid, 21% were DNA tetraploid and 8% were DNA aneuploid. Among microsatellite stable tumours, 24% were DNA diploid, 15% were DNA tetraploid and 61% were DNA aneuploid.

Conclusion: For patients presenting with stage II disease, genomic instability as detected by DNA image cytometry has the potential to provide a useful biomarker for relapse and cancer-related death following surgery with curative intent.

MeSH terms

Adult
Aged
Aged, 80 and over
Aneuploidy
Colorectal Neoplasms / diagnosis*
Colorectal Neoplasms / genetics*
Colorectal Neoplasms / pathology
DNA, Neoplasm / genetics
Disease-Free Survival
Female
Humans
Kaplan-Meier Estimate
Male
Microsatellite Instability*
Middle Aged
Neoplasm Recurrence, Local / genetics
Neoplasm Staging
Norway
Prognosis*

Substances

DNA, Neoplasm