If either the BRAF V600E mutation or MLH1 promoter methylation is found in a microsatellite unstable tumor, then the tumor is probably sporadic and further work-up for HNPCC may not be warranted.
If no BRAF mutation or MLH1 methylation is found, then the tumor may be either sporadic or inherited, and further work-up for HNPCC is recommended. It is known now that the BRAF p.V600E mutation is detected in more than 70% tumors with loss of MLH1 due to promoter hypermethylation but is rarely detected in tumors with a germline MLH1 gene mutation. Thus, a germline mutation within the MLH1 gene is very unlikely in this case.
When testing is performed for therapeutic selection, especially for the efficacy of EGFR-targeted therapies in colorectal cancer, tumors lacking KRAS and BRAF might not be the best choice and may have limited therapeutic value for this patient.
Detection of BRF V600 mutation in melanoma might indicate good respond to BRAF targeted therapy.