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

Axel Walther ^1*, Richard Houlson ² and Ian Tomlinson ¹

¹ London Research Institute, Cancer Research UK, United Kingdom
² Institure of Cancer Research, Sutton, United Kingdom

^* To whom correspondence should be addressed. E-mail: axel.walther{at}cancer.org.uk.

Accepted 19 February 2008

Abstract

Introduction 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, we have reviewed and pooled data from published studies.

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 hazard ratio for death (HR).

Results Sixty-three 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 of 1.35-1.55, p<0.001). In patients with stage II-III CRCs, the HR was 1.45 (95% CI 1.27-1.65, p<0.001). The effect was similar for progression-free survival (HR=1.71, 95% CI 1.51-1.94, p<0.001). There was no evidence of significant inter-study 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.