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Genetic and epigenetic classifications define clinical phenotypes and determine patient outcomes in colorectal cancer†
Article first published online: 28 SEP 2009
Copyright © 2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.
British Journal of Surgery
Volume 96, Issue 10, pages 1196–1204, October 2009
How to Cite
Sanchez, J. A., Krumroy, L., Plummer, S., Aung, P., Merkulova, A., Skacel, M., DeJulius, K. L., Manilich, E., Church, J. M., Casey, G. and Kalady, M. F. (2009), Genetic and epigenetic classifications define clinical phenotypes and determine patient outcomes in colorectal cancer. Br J Surg, 96: 1196–1204. doi: 10.1002/bjs.6683
- Issue published online: 28 SEP 2009
- Article first published online: 28 SEP 2009
- Manuscript Accepted: 16 APR 2009
- Cleveland Clinic Crile Foundation
A molecular classification of colorectal cancer has been proposed based on microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and mutations in the KRAS and BRAF oncogenes. This study examined the prevalence of these molecular classes, and differences in clinical presentation and outcome.
Demographics, tumour characteristics and survival were recorded for 391 subjects with colorectal cancer. Tumour DNA was analysed for MSI (high (MSI-H) or microsatellite stable (MSS)), CIMP (high (CIMP-H) or no (CIMP-neg)) and BRAF and KRAS mutations. Clinical differences between four phenotypes were examined.
Most tumours were MSS/CIMP-neg (69·8 per cent), with a nearly equal distribution of MSI-H/CIMP-H, MSI-H/CIMP-neg and MSS/CIMP-H types. MSS/CIMP-neg tumours were less likely to be poorly differentiated (P = 0·009). CIMP-H tumours were more common in older patients (P < 0·001). MSI-H/CIMP-H tumours had a high frequency of BRAF mutation and a low rate of KRAS mutation; the opposite was true for MSS/CIMP-neg tumours (P < 0·001). The four molecular phenotypes tended towards divergent survival (P = 0·067 for stages 1–III). MSI-H cancers were associated with better disease-free survival (hazard ratio 2·00 (95 per cent confidence interval 1·03 to 3·91); P = 0·040).
Colorectal cancers are molecularly and clinically heterogeneous. These different molecular phenotypes may reflect variable prognosis. Copyright © 2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.