ArticleThe American journal of surgical pathology2013
BRAFV600E immunohistochemistry facilitates universal screening of colorectal cancers for Lynch syndrome.
Article in The American journal of surgical pathology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 2 of them syntheses that pooled it.
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Who cites it
51 citing papers in PubMed, 2 syntheses or guidelines pooled it, 146 citations in OpenAlex.
- Rate of dissemination and prognosis in early and advanced stage colorectal cancer based on microsatellite instability status: systematic review and meta-analysis.International journal of colorectal disease · 2021Pooled it
- Diagnostic Accuracy of BRAF Immunohistochemistry in Colorectal Cancer: a Meta-Analysis and Diagnostic Test Accuracy Review.Pathology oncology research : POR · 2016Pooled it
- Proficiency test of BRAF immunohistochemistry as a surrogate marker of p.V600E mutation: Assessment of staining and interpretation quality in Taiwan.Virchows Archiv : an international journal of pathology · 2026Article
- Canadian consensus for the assessment and testing of Lynch syndrome.Journal of medical genetics · 2025Article
- Unveiling pembrolizumab effectiveness in diverse subtypes of MSI-high endometrial cancers.Journal of gynecologic oncology · 2024Article
- Current and Future Trends of Colorectal Cancer Treatment: Exploring Advances in Immunotherapy.Cancers · 2024Review
- Identifying primary and secondary MLH1 epimutation carriers displaying low-level constitutional MLH1 methylation using droplet digital PCR and genome-wide DNA methylation profiling of colorectal cancers.Clinical epigenetics · 2023Article
- Article
- A Focused Clinical Review of Lynch Syndrome.Cancer management and research · 2023Review
- Usefulness of BRAF VE1 immunohistochemistry in non-small cell lung cancers: a multi-institutional study by 15 pathologists in Korea.Journal of pathology and translational medicine · 2022Article
- Identifying patients with Lynch syndrome using a universal tumor screening program in an integrated healthcare system.Hereditary cancer in clinical practice · 2022Article
- Clinicopathological characteristics of high microsatellite instability/mismatch repair-deficient colorectal cancer: A narrative review.Frontiers in immunology · 2022Review
- Real-world outcome of universal screening for Lynch syndrome in Japanese patients with colorectal cancer highlights the importance of targeting patients with young-onset disease.Molecular and clinical oncology · 2021Article
- BRAF V600E and Mismatch Repair Proteins Expression in Sporadic Young-onset Colorectal Cancer in Kelantan, Malaysia.Oman medical journal · 2021Article
- Enhancing the landscape of colorectal cancer using targeted deep sequencing.Scientific reports · 2021Article
- Diagnosis of Lynch Syndrome and Strategies to Distinguish Lynch-Related Tumors from Sporadic MSI/dMMR Tumors.Cancers · 2021Review
- NTRK gene rearrangements are highly enriched in MLH1/PMS2 deficient, BRAF wild-type colorectal carcinomas-a study of 4569 cases.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2020Article
- Multiplex detection of ctDNA mutations in plasma of colorectal cancer patients by PCR/SERS assay.Nanotheranostics · 2020Article
- Report from the 20th annual Western Canadian Gastrointestinal Cancer Consensus Conference; Saskatoon, Saskatchewan; 28-29 September 2018.Current oncology (Toronto, Ont.) · 2019Article
- Off-label use of common predictive biomarkers in gastrointestinal malignancies: a critical appraisal.Diagnostic pathology · 2019Review
Corrections and comments
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Authors and funding
19 authors at 4 institutions in 1 country.
Funding
Abstract
BRAFV600E mutation in microsatellite-unstable (MSI) colorectal carcinomas (CRCs) virtually excludes Lynch syndrome (LS). In microsatellite-stable (MSS) CRCs it predicts poor prognosis. We propose a universal CRC LS screening algorithm using concurrent reflex immunohistochemistry (IHC) for BRAFV600E and mismatch-repair (MMR) proteins. We compared BRAFV600E IHC with multiplex polymerase chain reaction (PCR) and matrix-assisted laser desorption/ionization-time of flight mass spectrometry in 216 consecutive CRCs from 2011. Discordant cases were resolved with real-time PCR. BRAFV600E IHC was performed on 51 CRCs from the Australasian Colorectal Cancer Family Registry (ACCFR), which were fully characterized for BRAF mutation by allele-specific PCR, MMR status (MMR IHC and MSI), MLH1 promoter methylation, and germline MLH1 mutation. We then assessed MMR and BRAFV600E IHC on 1403 consecutive CRCs. By matrix-assisted laser desorption/ionization-time of flight mass spectrometry 15 cases did not yield a BRAF result, whereas 38/201 (19%) were positive. By IHC 45/216 (20%) were positive. Of the 7 discordant cases, real-time PCR confirmed the IHC result in 6. In the 51 CRCs from the ACCFR, IHC was concordant with allele-specific PCR in 50 cases. BRAFV600E and MSI IHC on 1403 CRCs demonstrated the following phenotypes: BRAF/MSS (1029 cases, 73%), BRAF/MSS (98, 7%), BRAF/MSI (183, 13%), and BRAF/MSI (93, 7%). All 11/1403 cancers associated with proven LS were BRAF/MSI. We conclude that BRAF IHC is highly concordant with 2 commonly used PCR-based BRAFV600E assays; it performed well in identifying MLH1 mutation carriers from the ACCFR and identified all cases of proven LS among the 1403 CRCs. Reflex BRAFV600E and MMR IHC are simple cheap tests that facilitate universal LS screening and identify the poor prognosis of the BRAFV600E-mutant MSS CRC phenotype.
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