What is the abnormality in MSI unstable sporadic CRCs?
These constitute approximately 12% to 15% of CRCs. The MSI-H is caused by somatic inactivation of hMLH1 mismatch repair gene due to hypermethylation of the promoter region preceding the gene sequence, whereas in HNPCC, the instability is due to germline mutation in the MMR genes. Most of the sporadic ones show BRAF mutations ( V600E mutation of BRAF oncogene). The histologic findings are similar to those seen in HNPCC.