Abstract / Summary
Background and Objectives: BRAF p.V600E status has diagnostic, prognostic, and therapeutic relevance in colorectal carcinoma. Molecular assays remain the reference methods, whereas mutation-specific BRAF (VE1 clone) immunohistochemistry offers a rapid tissue-based alternative. We evaluated VE1–molecular concordance and factors affecting diagnostic performance. Materials and Methods: PubMed/MEDLINE, Scopus, and Web of Science were searched in August 2025 and updated on 27 July 2026 for English-language original studies published from 2014 through the update date. Eligible reports applied VE1 and a recognized molecular reference method to the same colorectal carcinoma specimens or a defined overlapping cohort. Study selection and data extraction were performed by one reviewer and independently verified by a second reviewer. Risk of bias and applicability were assessed at the estimate level with QUADAS-3. Because of substantial clinical and methodological heterogeneity, no meta-analysis was performed, and the findings were synthesized descriptively. Results: Of 704 database records, 358 unique records were screened; 38 full-text reports were assessed and 28 were included. Twenty-three reports or defined subcohorts provided complete or clearly reconstructible 2 × 2 comparisons. Sensitivity ranged from 74.6% to 100% and specificity from 66.7% to 100%. Most optimized protocols exceeded 90% for both measures, whereas selected sampling, weak or focal staining, post hoc thresholds, protocol effects, and selective molecular verification reduced reliability. Conclusions: VE1 immunohistochemistry may provide a rapid, locally validated triage method for detecting BRAF p.V600E in colorectal carcinoma. However, substantial heterogeneity and recurrent risk-of-bias concerns limit the generalizability of the available estimates and do not support universal substitution for molecular testing. Equivocal, technically inadequate, or clinically discordant results require molecular clarification.