The MMR status of a patient’s tumor provides additional information about a patient’s individualized prognosis. Studies have shown that Stage II colon cancer patients with MMR-deficient (MMR-D) tumors have a lower risk of recurrence compared to patients with MMR-proficient (MMR-P) tumors.4 Knowing their MMR status may help Stage II colon cancer patients and their doctors make more informed decisions about how to best treat their disease.
In MMR-P tumors, an intact MMR pathway corrects errors in DNA replication that occur routinely during cell division. In MMR-D tumors, the MMR pathway is compromised. Approximately 15% of stage II colon cancer patients have tumors that are MMR deficient. MMR deficiency is also observed in Lynch Syndrome, a hereditary form of colon cancer, though the majority of patients with MMR-D tumors do not have Lynch Syndrome. However, patients with MMR-D tumors should speak with their doctors about further testing.
Recent studies have also suggested that patients with MMR-D colon cancer may be resistant to 5-FU based chemotherapy, but this remains an ongoing question of study.5 Taken together, these findings have led to the consideration of MMR testing for assessment of recurrence risk in select stage II colon cancer patients in the NCCN Colon Cancer clinical practice guidelines, although its clinical application to adjuvant treatment decision-making continues to evolve.
Tumor MMR status can be ascertained in two different ways: immunohistochemistry (IHC) to identify protein expression of known proteins in the MMR pathway or DNA-based PCR analysis to assess the presence of microsatellite instability. Both methods have been shown to be highly concordant, with concordance rates of up to 97% reported in the literature.6 Based on recent data, Genomic Health will begin providing MMR testing for recurrence risk assessment as part of the Oncotype DX service in late 2011.
4. Kerr D, Gray R, Quirke P, et al; A quantitative multi-gene RT-PCR assay for prediction of recurrence in stage II colon cancer: selection of the genes in 4 large studies and results of the independent, prospectively-designed QUASAR validation study; American Society of Clinical Oncology (ASCO) Annual Meeting, 2009.
5. Sargent; Journal of Clinical Oncology, 2010
6. Bertagnolli; Journal of Clinical Oncology, 2010