Correlative Science Studies in Colon Cancer a Companion Study to CALGB 9581 and 89803
- To assess the ability of a prognostic gene expression signature to stratify stage II
colorectal cancer patients into those who will experience relapse within five years
post surgery (high risk) and those who will experience five-year disease-free survival
(low risk), without additional treatment.
- To correlate the methylation status of the individual genes, MLH1, WRN, and MGMT with
- To correlate the CIMP status (CIMP vs nonCIMP) of the tumors with survival.
- To correlate the expression status of the individual genes based on the immunostaining
results with survival.
- To correlate the expression of the functional groups of proteins in which survival is
correlated with the expression of the MLH1 functional group (MLH1, PMS2, and MSH2), the
WRN functional group (WRN, MRE11, and MLH1), and the MGMT functional group (MGMT, MYH,
and OGG) with survival (the loss of expression of any member of each functional group
will be scored as indicating loss of function of the functional group).
- To correlate the mutation status of MRE11 in MSI colorectal cancers with disease-free
survival and overall survival.
- To define the association of CIMP and methylated genes with other genetic alterations
and tumor-specific characteristics.
OUTLINE: This is a multicenter, companion study.
Tissue samples from patients are analyzed for K-ras mutations; COX-2, phospho-AKT, and VEGF
overexpression; microvessel density; association of genomic instability with microsatellite
instability and p53 mutations; and methylation status of MLH1, MGMT, and WRN and to identify
prognostic biomarkers by LINE-1 hypomethylation, PIK3CA mutation, BRAF mutation, fatty acid
sysnthase (FASN) expression, and vitamin D receptor (VDR) expression.Techniques used include
immunohistochemistry, PCR, RT-PCR, and gel electrophoresis.
Associate methylated and silenced DNA repair genes, MLH1, WRN, or MGMT, or CIMP colorectal cancers with the clinical endpoints of overall (OS) and disease-free survival (DFS)
Monica M. Bertagnolli, MD
Dana-Farber/Brigham and Women's Cancer Center
United States: Federal Government