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Prognostic/Predictive molecular markers in colorectal cancer.

Clinicopathologic staging often does not provide sufficient prognostic information to determine, for example, which patients with stage II colon cancer have risk of progression sufficient to warrant adjuvant therapy. Strategies to improve prognostic assessment and to provide the ability to determine likelihood of response to therapies include development of molecular prognostic and predictive markers. The effect of chromosome 18q21 loss of heterozygosity (LOH) and microsatellite instability in stage II colon cancer is being evaluated in an adjuvant therapy trial. A number of germline polymorphisms (eg, in genes involved in angiogenesis) have been found to be associated with different degrees of risk of recurrence. Microarray techniques have led to the identification and validation of a number of molecular signatures that appear to discriminate risk within clinicopathologic stages of disease, and candidate gene identification approaches have yielded a large number of genes associated with recurrence risk. A great deal of work remains to be done in validating markers/signatures in larger populations, standardizing analysis procedures, and testing prognostic/predictive accuracy in prospective clinical trials.