QUASAR results: The prognostic validity of a colon cancer recurrence score and the role of multigene profiles in determining risk

Great effort is being made in the field of molecular diagnostics to develop "tools" that may allow selection of patients who would benefit most (or least) from chemotherapy. Several molecular approaches have been used in attempts to develop clinically meaningful indices, ranging from immunohistochemical assessment of individual protein expression (eg, KRAS, p53, thymidylate synthase), DNA mutations as measured by chromosomal and microsatellite instability (MSI), and genome-wide association studies searching for single nucleotide polymorphisms, to exploration of RNA expression using modern chip-based technology. There now are data that shift the paradigm for management of stage II colon cancer, and a novel reverse transcriptase polymerase chain reaction multigene assay, which may be performed in paraffin-embedded tumor tissue, may become established as a prognostic tool of choice. In the context of stage, grade, nodes examined, and MSI status, the QUASAR study yielded 18 genes (seven prognostic, six predictive, and five reference genes), and separate prognostic recurrence score and predictive treatment score signatures have been developed. We believe the recurrence score provides an individualized assessment of recurrence risk and will have the greatest clinical utility when used in conjunction with T stage and mismatch repair status, particularly for most patients (70%) for whom those markers are uninformative. © Springer Science+Business Media, LLC 2010.