Prognostic significance of defective mismatch repair and BRAF V600E in patients with colon cancer
Open accessAbstract
Purpose: Colon tumors with defective DNA mismatch repair (dMMR) have a well-characterized phenotype and accounts for ∼15% to 20% of sporadic colon cancer as well as those colon cancer patients with Lynch syndrome. Although the presence of dMMR seems to be a favorable prognostic marker, data suggest that these patients do not respond as well to adjuvant chemotherapy. Experimental Design: In this study, we examined the prognostic significance of tumor MMR deficiency and the presence of a specific mutation in BRAF (V600E) in a group of patients (n = 533) who participated in a randomized prospective clinical trial through the North Central Cancer Treatment Group. Results: Tumors with dMMR were found to be associated with higher tumor grade (P = 0.001), proximal location (P < 0.0001), and improved overall and disease-free survival (P = 0.05 and 0.04, respectively). Among all cases examined, evaluation of the BRAF V600E mutation status revealed no statistically significant differences in either disease-free or overall survival. Patients were then grouped into four categories for further analysis: dMMR/BRAF(−), dMMR/BRAF(+), pMMR/BRAF(−), and pMMR/BRAF(+). The dMMR/BRAF(−) group had a significantly improved overall survival (5-year overall survival of 100% versus 73%, P = 0.002) compared with all others. The remaining three groups had very similar survival outcomes. An additional cohort of tumors previously classified as having dMMR were also tested for the BRAF V600E alteration. Results remained significant (P = 0.006) when the two groups were combined for analysis. Conclusions: Overall, these data suggest that the underlying molecular etiology of those tumors having dMMR may influence the disease outcome in these patients.
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Identifying the BRAFV600E mutation indicates a poorer outcome in both stage II and stage III colorectal cancer cases.
“Additionally, identifying this mutation indicates a poorer outcome in both stage II and III CRC cases [48]”
From Current and Future Trends of Colorectal Cancer Treatment: Exploring Advances in Immunotherapy (2024) · cites this paper as [48]
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- Authors
- French, A. J., Sargent, D. J., Burgart, L. J., Foster, N. R., Kabat, B. F., Goldberg, R., Shepherd, L., Windschitl, H. E., & Thibodeau, S. N.
- Affiliations
- 1Laboratory Medicine and Pathology and
- Mayo Clinic (US)
- Abbott Northwestern Hospital (US)
- University of North Carolina at Chapel Hill (US)
- Queen's University (CA)
- CentraCare Health System (US)
- ORCID
- Venue
- Clinical Cancer Research
- Published
- 2008-06-01
- Volume
- 14
- Issue
- 11
- Pages
- 3408-3415
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- PMC
- PMC2674786
- OpenAlex
- W2140728431
- Cited by
- 251
- References
- 41
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 15 · 2023: 14 · 2022: 8 · 2021: 12 · 2020: 13 · 2019: 9 · 2018: 15 · 2017: 9 · 2016: 17 · 2015: 19 · 2014: 22 · 2013: 21 · 2012: 26
- FWCI
- 9.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (CA-25224)
- National Cancer Institute (CA 60117, (CA-25224, U10CA025224, R01CA060117)
- 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
- colon cancer, BRAF V600E mutation, prognostic factors, Lynch syndrome, overall survival, disease-free survival, tumor grade, proximal colon tumors, adjuvant chemotherapy response
- MeSH terms
- Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Colonic Neoplasms, Female, Humans, Immunohistochemistry, Male, Middle Aged, Mutation, Prognosis, Biomarkers, Tumor, Polymerase Chain Reaction, Clinical Trials, Phase III as Topic, Drug Resistance, Neoplasm, Proto-Oncogene Proteins B-raf, Kaplan-Meier Estimate, DNA Mismatch Repair
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