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


CONCLUSIONS
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.
Walther
A
A
Molecular and Population Genetics Laboratory, London Research Institute, Cancer Research UK, London, UK. axel.walther@cancer.org.uk
Houlston
R
R
Tomlinson
I
I
D043171:Chromosomal Instability; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D006801:Humans; D009367:Neoplasm Staging; D011379:Prognosis; D017594:Publication Bias; D016019:Survival Analysis; D016896:Treatment Outcome