Association between chromosomal instability and prognosis in colorectal cancer: a meta-analysis
- 1Molecular and Population Genetics Laboratory, London Research Institute, Cancer Research UK, London, UK
- 2Section 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;
- Revised 14 February 2008
- Accepted 19 February 2008
- Published Online First 25 March 2008
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.
Funding: This study was supported by grants from Cancer Research UK (AW, IT) and the Association for International Cancer Research (RH)
Competing interests: None.