BRAF V600E-specific immunohistochemistry for the exclusion of Lynch syndrome in MSI-H colorectal cancer.

摘要: The differentiation between hereditary and sporadic microsatellite-unstable (MSI-H) colorectal cancer is a crucial step in Lynch syndrome diagnostics. Within MSI-H cancers, the BRAF V600E mutation strongly associated with origin. Here, we asked whether V600E-specific immunohistochemistry (clone VE1) helpful separating from syndrome-associated cancers. To that end, performed VE1 sequencing series of 91 specimens patients tested for syndrome. Concordance molecular status was observed 90 (98.9%) samples. All 11 tumors classified as mutation-positive by Sanger were immunopositive, 79 (98.8%) 80 wild type showed negative staining. VE1-positive MLH1- PMS2-negative immunohistochemistry. None mismatch repair (MMR) gene germline carriers (n = 28) displayed positive staining, indicating mutation-specific immunostaining has low risk excluding analysis. In conclusion, implementation able to detect BRAF-mutated cancers sensitivity 100% specificity 98.8%. Among MLH1-negative rate lesions 21%, offering exclusion these MMR testing. Therefore, suggest integration into diagnostic panel