A Walther1, R Houlston, I Tomlinson. 1. Molecular and Population Genetics Laboratory, London Research Institute, Cancer Research UK, London, UK. axel.walther@cancer.org.uk
Abstract
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.
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.
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