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Updated: Jul 5, 2026
Evaluation of Colorectal Cancer Risk and Prevalence by Stool DNA Integrity Detection
Published on: June 8, 2020
Cost analysis of biomarker testing for mismatch repair deficiency in node-positive colorectal cancer
E Barrow1, R McMahon, D G Evans
1Department of General Surgery, Manchester Royal Infirmary, St Mary's Hospital, Manchester, UK. emma.barrow@doctors.org.uk
Background:
Microsatellite instability (MSI) in colorectal cancer is caused by defective DNA mismatch repair (MMR). It is present in 15 per cent of sporadic colorectal cancers owing to epigenetic mutL homologue 1 (MLH1) inactivation. The evidence suggests that patients with tumours caused by defective DNA MMR do not benefit from 5-fluorouracil (5-FU)-based chemotherapy.
Methods:
The proportion of cancers with defective DNA MMR identified by MSI analysis or immunohistochemistry was calculated from published data. The cost of analysis was compared with the potential savings if 5-FU-based chemotherapy was not administered to these patients.
Results:
Some 16.3 per cent of sporadic colorectal cancers had defective DNA MMR. Immunostaining for MLH1 and mutS homologue 2 (MSH2) had a sensitivity of 92.4 per cent and a specificity of 99.6 per cent for identifying MSI-high tumours. The strongest predictive variable was right-sidedness, with positive and negative predictive values of 0.329 and 0.948 respectively. If 5-FU-based chemotherapy were not administered, potential savings of up to pound 1.2 million per 1000 patients tested could be made. Costs would be higher if alternative chemotherapeutic regimens were substituted as a result of testing.
Conclusion:
Knowledge of MMR status may enable participation in trials of non-5-FU-based chemotherapy. The cost of MMR testing may be offset by more efficient use of chemotherapy.
Insights
Microsatellite instability (MSI) in colorectal cancer, caused by DNA mismatch repair (MMR) defects, means patients may not benefit from 5-fluorouracil (5-FU) chemotherapy. MMR testing can identify these cases, potentially saving costs and guiding treatment choices.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Microsatellite instability (MSI) in colorectal cancer arises from deficient DNA mismatch repair (MMR).
- Approximately 15% of sporadic colorectal cancers exhibit MSI due to epigenetic silencing of the MLH1 gene.
- Evidence indicates that patients with MMR-deficient tumors do not benefit from 5-fluorouracil (5-FU)-based chemotherapy.
Purpose of the Study:
- To determine the prevalence of defective DNA MMR in sporadic colorectal cancers.
- To evaluate the cost-effectiveness of MMR testing by comparing analysis costs with potential savings from avoiding ineffective 5-FU chemotherapy.
Main Methods:
- Systematic review of published data to calculate the proportion of colorectal cancers with defective DNA MMR.
- Comparison of the costs associated with MSI analysis or immunohistochemistry (IHC) versus potential chemotherapy savings.
Main Results:
- Defective DNA MMR was identified in 16.3% of sporadic colorectal cancers.
- Immunohistochemistry for MLH1 and MSH2 demonstrated high sensitivity (92.4%) and specificity (99.6%) for detecting MSI-high tumors.
- Potential savings of up to £1.2 million per 1000 patients tested could be achieved by withholding 5-FU chemotherapy from patients with MMR-deficient tumors.
Conclusions:
- MMR status testing can identify colorectal cancer patients unlikely to benefit from 5-FU chemotherapy.
- MMR testing may facilitate enrollment in clinical trials for alternative, non-5-FU-based chemotherapy regimens.
- The cost of MMR testing can be offset by optimizing chemotherapy utilization and avoiding ineffective treatments.
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