Colorectal cancer

Association between chromosomal instability and prognosis in colorectal cancer: a meta-analysis

A Walther¹, R Houlston², I Tomlinson¹

¹ Molecular and Population Genetics Laboratory, London Research Institute, Cancer Research UK, London, UK
² Section of Cancer Genetics, Institute of Cancer Research, Sutton, UK

Dr A Walther, Molecular and Population Genetics, London Research Institute, Cancer Research UK, 44 Lincoln’s Inn Fields, London WC2A 3PX, UK; axel.walther{at}cancer.org.uk

Background: Several studies have suggested that microsatellite instability (MSI) resulting from defective DNA mismatch repair confers a better prognosis in colorectal cancer (CRC). Recently, however, data have suggested this is secondary to the effects of ploidy/chromosomal instability (CIN). To estimate the prognostic significance of CIN for survival, data from published studies have been reviewed and pooled.

Methods: Studies stratifying survival in CRC by CIN status were identified by searching PubMed and hand-searching bibliographies of identified studies. Two reviewers confirmed study eligibility and extracted data independently, and data were pooled using a fixed-effects model. The principal outcome measure was the HR for death.

Results: 63 eligible studies reported outcome in 10 126 patients, 60.0% of whom had CIN+ (aneuploid/polyploid) tumours. The overall HR associated with CIN was 1.45 (95% CI 1.35 to 1.55, p<0.001). In patients with stage II–III CRCs, the HR was 1.45 (95% CI 1.27 to 1.65, p<0.001). The effect was similar for progression-free survival (HR = 1.71, 95% CI 1.51 to 1.94, p<0.001). There was no evidence of significant interstudy heterogeneity.

Conclusion: CIN is associated with a worse prognosis in CRC, and should be evaluated as a prognostic marker, together with MSI status, in all clinical trials, particularly those involving adjuvant therapies.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

Relevant Article

Digest

Robin Spiller and Magnus Simren
Gut 2008 57: i. [Extract] [Full Text] [PDF]

This article has been cited by other articles:

• TRIANTAFILLIDIS, J. K., NASIOULAS, G., KOSMIDIS, P. A. (2009). Colorectal Cancer and Inflammatory Bowel Disease: Epidemiology, Risk Factors, Mechanisms of Carcinogenesis and Prevention Strategies. Anticancer Res 29: 2727-2737 [Abstract] [Full Text]  
• Ogino, S., Nosho, K., Kirkner, G. J, Kawasaki, T., Meyerhardt, J. A, Loda, M., Giovannucci, E. L, Fuchs, C. S (2009). CpG island methylator phenotype, microsatellite instability, BRAF mutation and clinical outcome in colon cancer. Gut 58: 90-96 [Abstract] [Full Text]  
• Corver, W. E., Middeldorp, A., ter Haar, N. T., Jordanova, E. S., van Puijenbroek, M., van Eijk, R., Cornelisse, C. J., Fleuren, G. J., Morreau, H., Oosting, J., van Wezel, T. (2008). Genome-wide Allelic State Analysis on Flow-Sorted Tumor Fractions Provides an Accurate Measure of Chromosomal Aberrations. Cancer Res. 68: 10333-10340 [Abstract] [Full Text]