Gene profiling in early stage disease.

Although we have made steady progress in the adjuvant chemotherapy of colorectal cancer, it is clear that any population benefits accrued stem from overtreatment of the majority of patients. For example, we have to treat 100 stage II patients to cure 3 or 4, while accepting that up to 40% of those treated will suffer significant toxicity and all will face the distinct social (and often financial) inconvenience of outpatient chemotherapy for 6 months. This has prompted much effort in the field of molecular diagnostics to develop "tools," which may allow selection of patients who will benefit most (or least) from chemotherapy. The majority of translational research to identify prognostic and/or predictive biomarkers has been somewhat confounded by studies of small sample size, insufficient statistical power, variable methodology, and incomplete clinical data sets, so other than conventional histopathological staging, there are no widely accepted molecular markers of prognosis and prediction. A novel reverse transcriptase polymerase chain reaction multigene assay, performed on RNA extracted from paraffin-embedded tumor tissue has been validated in a series of 1436 patients with stage II colon cancer and was found to be predict recurrence risk (HR/25 units = 1.58; 95% CI, 1.15-2.15; P = 0.004). This may become established as a prognostic tool of choice for stage II colon cancer.