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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.

Original publication

DOI

10.1136/gut.2007.135004

Type

Journal article

Journal

Gut

Publication Date

07/2008

Volume

57

Pages

941 - 950

Keywords

Chromosomal Instability, Colorectal Neoplasms, Humans, Neoplasm Staging, Prognosis, Publication Bias, Survival Analysis, Treatment Outcome