Extended Data Fig. 9: Mutation frequencies of RNF43 and APC genes in MSS status and immunohistochemical analysis against human β-catenin of mCRC^BRAF-V600E tumor samples.

A, B) Mutation frequencies of RNF43 and APC genes, and response status from patients with mCRC^BRAF-V600E with MSS tumors from the discovery (A) and validation (B) cohorts. Chi-square test was used for the statistical analysis. Abbreviations: CR, complete response; MSS, microsatellite stable; PD, progressive disease; PR, partial response; SD, stable disease. C–D) Immunohistochemical analysis against human β-catenin was performed in MSS-RNF43^wild-type, MSS-RNF43^mutated, and MSI-RNF43^mutated mCRC^BRAF-V600E tumor samples (n = 33) to search for potential differential pattern in total expression or cellular localization of β-catenin protein. No correlation was found between β-catenin protein expression levels (0, no staining; 1, weak; 2, moderate; and 3, strong) and cellular localization (cytoplasm, membrane, nucleus) with response to anti-BRAF/EGFR ± combinatorial therapies. Representative immunohistochemistry for β-catenin with strong membrane positivity, weak-moderate cytoplasmic positivity, and few weak nucleus positivity (magnification 40x) (C) and strong-moderate nuclear and cytoplasmic positivity (D) (magnification 40x).