Microsatellite Instability in Colorectal Cancer and Its Link to Thymidylate Synthase and Dihydropyrimidine Dehydrogenase Expression
Author Information
Author(s): Søren A. Jensen, Ben Vainer, Mogens Kruhøffer, Jens B. Sørensen
Primary Institution: Rigshospitalet, Copenhagen University Hospital
Hypothesis
The study evaluates the association of microsatellite instability (MSI) and mismatch repair (MMR) status with outcomes and with thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) expression in colorectal cancer.
Conclusion
MSI colorectal carcinomas have a favorable outcome mainly due to tumor biology and less so to the response to 5-fluorouracil therapy.
Supporting Evidence
- MSI was found in 43 (13.8%) tumors.
- Absence of repair protein expression was assessed in 52 (17.0%) tumors.
- MSI tumors had a significantly lower risk of recurrence and death compared to MSS tumors.
- A direct relationship between MSI and TS intensity was found (P = 0.001).
Takeaway
This study found that colorectal cancer with microsatellite instability tends to do better than stable cancer, mostly because of how the tumor behaves, not just because of treatment.
Methodology
The study assessed MSI in tumor specimens and analyzed the expression of MMR proteins, TS, and DPD in relation to patient outcomes.
Potential Biases
Potential biases in treatment groups and the retrospective design may influence the findings.
Limitations
The study's retrospective nature and potential biases in treatment allocation may affect the results.
Participant Demographics
The study included 340 patients with colorectal cancer stages II-IV, with a bimodal age distribution favoring older patients.
Statistical Information
P-Value
0.0007
Confidence Interval
95% CI: 0.2–0.7
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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