BRAFV600E immunohistochemistry in conjunction with mismatch repair status predicts survival in patients with colorectal cancer
Open accessAbstract
Immunohistochemistry has recently been validated for the detection of the BRAFV600E mutation across a range of tumor types. In colorectal carcinoma, the presence of the BRAFV600E mutation can be used to virtually exclude Lynch syndrome in mismatch repair-deficient tumors. In mismatch repair-proficient tumors, BRAFV600E mutation assessed by molecular methods has been proposed as a poor prognostic factor. We investigated whether combined BRAFV600E and mismatch repair status assessment by immunohistochemistry alone can be used as a prognostic marker in the routine clinical setting. We performed immunohistochemistry for BRAFV600E, MLH1, PMS2, MSH2, and MSH6 on 1426 consecutive unselected colorectal carcinomas. Ninety-one (6.4%) carcinomas were mismatch repair-proficient and BRAFV600E mutant, and these tumors demonstrated a significantly worse 5-year survival of 49.7% compared with mismatch repair-proficient BRAF wild type (74.1% of tumors, 65.4% survival), mismatch repair-deficient BRAFV600E mutant (12.9% of tumors, 70.1% survival), and mismatch repair-deficient BRAF wild type (6.6% of tumors, 73.6% survival). The poor survival was confirmed by univariate analysis (P<0.01) but fell away in multivariate analysis (P=0.68) because of the strong effect of tumor stage and age on overall survival. We conclude that in addition to its utility in screening for Lynch syndrome, reflex BRAFV600E and mismatch repair assessment by immunohistochemistry can be used as a powerful predictor of all-cause survival.
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dMMR/BRAFV600E-negative tumors exhibit improved overall survival compared to dMMR/BRAFV600E-positive and proficient MMR/BRAFV600E-negative or proficient MMR/BRAFV600E-positive tumors.
“Despite growing evidence indicating that dMMR/BRAFV600E(−) tumors exhibit improved overall survival (OS) compared to dMMR/BRAFV600E(+) and proficient MMR (pMMR)/BRAFV600E(−) or pMMR/BRAFV600E(+) tumors [49,51]”
From Current and Future Trends of Colorectal Cancer Treatment: Exploring Advances in Immunotherapy (2024) · cites this paper as [49]
The presence of the BRAFV600E mutation predicts an unfavorable prognosis in right-sided microsatellite stable colorectal cancer and undervalued effects of systemic treatment regardless of targeted therapy use.
“Specifically, the presence of the BRAFV600E mutation predicts an unfavorable prognosis in right-sided microsatellite stable (MSS) CRC and undervalued effects of systemic treatment regardless of the use of targeted therapy [49].”
From Current and Future Trends of Colorectal Cancer Treatment: Exploring Advances in Immunotherapy (2024) · cites this paper as [49]
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Current and Future Trends of Colorectal Cancer Treatment: Exploring Advances in Immunotherapy
Nikolouzakis, T. K., Chrysos, E., Docea, A. O., Fragkiadaki, P., Souglakos, J., Tsiaoussis, J., & Tsatsakis, A. (2024) · Cancers · doi:10.3390/cancers16111995 · Cited by 37 · see citing works
- Authors
- Toon, C. W., Chou, A., DeSilva, K., Chan, J., Patterson, J., Clarkson, A., Sioson, L., Jankova, L., & Gill, A. J.
- Affiliations
- The University of Sydney (AU)
- St Vincent's Hospital Sydney (AU)
- Royal North Shore Hospital (AU)
- Corresponding author
- Gill, Anthony J
- Venue
- Modern Pathology
- Publisher
- Elsevier BV
- Published
- 2014-05
- Volume
- 27
- Issue
- 5
- Pages
- 644-650
- ISSN
- 0893-3952 (ISSN-L)
- PMC
- PMC4021849
- OpenAlex
- W2124101136
- Cited by
- 59
- References
- 31
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2022: 3 · 2021: 3 · 2020: 5 · 2019: 7 · 2018: 6 · 2017: 5 · 2016: 9 · 2015: 8 · 2014: 8
- FWCI
- 6.23
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Modern Pathology (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- 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
- BRAF V600E mutation, mismatch repair deficiency, colorectal cancer, Lynch syndrome screening, MLH1, PMS2, MSH2, MSH6, prognostic factors, overall survival, immunohistochemistry
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Carcinoma, Colorectal Neoplasms, Hereditary Nonpolyposis, Female, Humans, Immunohistochemistry, Male, Middle Aged, Mutation, Colorectal Neoplasms, Survival Rate, Proto-Oncogene Proteins B-raf, Microsatellite Instability, DNA Mismatch Repair, Young Adult
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