Replication error phenotype, clinicopathological variables, and patient outcome in Dukes' B stage II (T3,N0,M0) colorectal cancer
- B Currana,
- K Lenehanb,
- H Mulcahyc,
- O Tigheb,
- M A Bennettb,
- E W Kaya,
- D P O'Donoghuec,
- M Leadera,
- D T Crokeb
- aDepartment of Pathology, Royal College of Surgeons in Ireland, Dublin, Republic of Ireland, bDepartment of Biochemistry, cGastroenterology and Liver Unit, St Vincent's University Hospital, Dublin, Republic of Ireland
- Dr D T Croke, Department of Biochemistry, The Royal College of Surgeons in Ireland, 123, St Stephen's Green, Dublin 2, Republic of Ireland.
- Accepted 18 August 1999
AIMS To examine the relation between the replication error (RER) phenotype and other genetic events, clinical features, and long term survival in patients with Dukes' B stage II (T3,N0,M0) colorectal cancer.
METHODS RER phenotype was investigated in 159 patients by PCR amplification of microsatellite marker loci on chromosomes 5q, 17p, 17q, and 18q from tumour DNA extracted from archival tissue. Data on activating c-Ki-ras mutations were available from a previous study. Immunohistochemical detection of p53 and c-erbB-2 expression was performed on paraffin wax embedded tissue.
RESULTS Of 159 colorectal cancers studied, 22 (14%) were RER+ while 137 (86%) were RER− for two or more loci. RER+ tumours were more commonly located in the right colon, tended to be larger than RER− tumours, and were more often poorly differentiated than RER− cancers. No significant associations were seen between RER status and the presence of a mutant c-Ki-ras gene, or between RER status and p53, c-erbB-2, or c-myc gene expression. Univariate survival analysis showed that outcome was similar in RER+ and RER− cases. Multivariate survival analysis showed that the relative risk of death for patients with RER+ cancers was 0.95 that of patients with RER− cancers.
CONCLUSIONS The results suggest that, while the RER phenotype may be associated with some differences in tumour pathology (site, size, differentiation), it is not associated with the genetic alterations studied or with significant differences in long term survival.
- colon cancer
- replication error phenotype
- microsatellite instability
- p53 expression
- Abbreviations used in this paper:
- hereditary non-polyposis colorectal cancer
- replication error