Insulin-like growth factor 2 messenger RNA binding protein 3 (IGF2BP3) is a marker of unfavourable prognosis in colorectal cancer
European Journal of Cancer, 08/01/2012
Lochhead P et al. – IGF2BP3 expression in colorectal cancer is associated with adverse clinical outcome. Our findings support a role for IGF2BP3 as a diagnostic and/or prognostic biomarker in colorectal cancer.Methods
- We evaluated IGF2BP3 expression by immunohistochemistry in 671 rectal and colon cancer cases that form part of a molecular pathological epidemiology database.
- Cox proportional hazards regression models were used to compute mortality hazard ratio (HR), adjusting for clinical, pathological and molecular features, including microsatellite instability, the CpG island methylator phenotype, LINE-1 methylation and KRAS, BRAF and PIK3CA mutations.
- Among 671 colorectal cancers, 234 (35%) tumours were positive for IGF2BP3.
- In contrast, normal colorectal epithelium was negative for IGF2BP3 in all 403 specimens of normal mucosa adjacent to carcinoma.
- IGF2BP3 positivity was associated with poor differentiation (p=0.0003), stage III-IV disease (p=0.0081), BRAF mutation (p=0.031), and LINE-1 hypomethylation (p=0.020). IGF2BP3 positivity was significantly associated with shorter colorectal cancer-specific [log-rank p<0.0001; multivariate HR, 1.37; 95% confidence interval (CI), 1.02–1.84] and overall survival (log-rank p=0.0004; multivariate HR, 1.32; 95% CI, 1.05–1.66).