A team from the USA investigated the molecular predictors of survival after adjuvant chemotherapy for colon cancer.
Loss of chromosomal material from chromosomes 18q, 17p, and 8p; cellular levels of p53 and p21WAF1/CIP1 proteins; and microsatellite instability as molecular markers were all evaluated.
The researchers analyzed tumor tissue from 460 patients with Stage III and high-risk Stage II colon cancer to determine the ability of these markers to predict survival. All patients had been treated with various combinations of adjuvant fluorouracil, leucovorin, and levamisole
Loss of heterozygosity at 18q was present in 155 of 319 cancers (49%).
High levels of microsatellite instability were found in 62 of 298 tumors (21%), and 38 of these 62 tumors (61%) had a mutation of the gene for the Type II receptor for transforming growth factor-beta1.
|Loss of heterozygosity at 18q in 49% of tumors.|
High levels of microsatellite instability in 21%.
|New England Journal of Medicine|
Five-year overall survival rates after fluorouracil-based chemotherapy were calculated.
Among patients with microsatellite-stable Stage III cancer, the survival rate was 74% in those whose cancer retained 18q alleles. The overall survival was 50% in those with loss of 18q alleles. The relative risk of death with loss at 18q was found to be 2.75.
The five-year survival rate among patients whose cancer had high levels of microsatellite instability was 74% in the presence of a mutated gene for the Type II receptor for TGF-beta1. If the tumor did not have this mutation, the survival rate was 46% (relative risk of death, 2.90).
Researcher Toshiaki Watanabe, of the Johns Hopkins University School of Medicine, Baltimore, concluded on behalf of the group, "Retention of 18q alleles in microsatellite-stable cancers point to a favorable outcome after adjuvant chemotherapy with fluorouracil-based regimens for Stage III colon cancer.
"Mutation of the gene for the Type II receptor for TGF-beta1 in cancers with high levels of microsatellite instability also increases survival rates."