Tumor Microsatellite-Instability Status as a Predictor of Benefit from Fluorouracil-Based Adjuvant Chemotherapy for Colon Cancer
Open accessAbstract
BACKGROUND: Colon cancers with high-frequency microsatellite instability have clinical and pathological features that distinguish them from microsatellite-stable tumors. We investigated the usefulness of microsatellite-instability status as a predictor of the benefit of adjuvant chemotherapy with fluorouracil in stage II and stage III colon cancer. METHODS: Tumor specimens were collected from patients with colon cancer who were enrolled in randomized trials of fluorouracil-based adjuvant chemotherapy. Microsatellite instability was assessed with the use of mononucleotide and dinucleotide markers. RESULTS: Of 570 tissue specimens, 95 (16.7 percent) exhibited high-frequency microsatellite instability. Among 287 patients who did not receive adjuvant therapy, those with tumors displaying high-frequency microsatellite instability had a better five-year rate of overall survival than patients with tumors exhibiting microsatellite stability or low-frequency instability (hazard ratio for death, 0.31 [95 percent confidence interval, 0.14 to 0.72]; P=0.004). Among patients who received adjuvant chemotherapy, high-frequency microsatellite instability was not correlated with increased overall survival (hazard ratio for death, 1.07 [95 percent confidence interval, 0.62 to 1.86]; P=0.80). The benefit of treatment differed significantly according to the microsatellite-instability status (P=0.01). Adjuvant chemotherapy improved overall survival among patients with microsatellite-stable tumors or tumors exhibiting low-frequency microsatellite instability, according to a multivariate analysis adjusted for stage and grade (hazard ratio for death, 0.72 [95 percent confidence interval, 0.53 to 0.99]; P=0.04). By contrast, there was no benefit of adjuvant chemotherapy in the group with high-frequency microsatellite instability. CONCLUSIONS: Fluorouracil-based adjuvant chemotherapy benefited patients with stage II or stage III colon cancer with microsatellite-stable tumors or tumors exhibiting low-frequency microsatellite instability but not those with tumors exhibiting high-frequency microsatellite instability.
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MSI phenotype has been proofed to have relative better survival.
“which has been proofed to have relative better survival43.”
From A tumor microenvironment-specific gene expression signature predicts chemotherapy resistance in colorectal cancer patients (2021) · cites this paper as [43]
SFM-C's better survival is probably because of enrichment of MSI phenotype.
“Moreover, although SFM-C displayed nonresponsive to FOLFIRI and FOLFOX, which was also consistent with previous studies suggesting MSI tumors barely responded to fluorouracil-based therapy42, it had better survival in this combined dataset probably because of the enrichment of MSI phenotype, which has been proofed to have relative better survival43.”
From A tumor microenvironment-specific gene expression signature predicts chemotherapy resistance in colorectal cancer patients (2021) · cites this paper as [43]
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- Authors
- Ribic, C. M., Sargent, D. J., Moore, M. J., Thibodeau, S. N., French, A. J., Goldberg, R. M., Hamilton, S. R., Laurent-Puig, P., Gryfe, R., Shepherd, L. E., Tu, D., Redston, M., & Gallinger, S.
- Affiliations
- Lunenfeld-Tanenbaum Research Institute (CA)
- Queen's University (CA)
- The University of Texas MD Anderson Cancer Center (US)
- Mount Sinai Hospital (CA)
- Brigham and Women's Hospital (US)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2003-07-17
- Volume
- 349
- Issue
- 3
- Pages
- 247-257
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC3584639
- OpenAlex
- W2127951115
- Cited by
- 2,160
- References
- 2
- Citations by year
- 2026: 35 · 2025: 40 · 2024: 80 · 2023: 67 · 2022: 86 · 2021: 96 · 2020: 119 · 2019: 115 · 2018: 118 · 2017: 92 · 2016: 97 · 2015: 110 · 2014: 112 · 2013: 107 · 2012: 115
- FWCI
- 52.24
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5u01ca060100-02)
- National Cancer Institute (CA-23318, (CA-25224, U10CA025224, CA60100, U10CA023318, U10CA021115, P50CA062924, CA 21115, CA 62924)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Oncology › Colorectal Cancer Surgical Treatments
- Keywords
- microsatellite instability, colon cancer, 5-fluorouracil, adjuvant chemotherapy, predictive biomarkers, stage II colon cancer, stage III colon cancer, overall survival, treatment response prediction
- MeSH terms
- Analysis of Variance, Antimetabolites, Antineoplastic, DNA Repair, DNA, Neoplasm, Fluorouracil, Follow-Up Studies, Humans, Neoplasm Staging, Prognosis, Colorectal Neoplasms, Survival Analysis, Chemotherapy, Adjuvant, Microsatellite Repeats, Base Pair Mismatch
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