Abstract
Hereditary nonpolyposis colorectal cancer (HNPCC) is an inherited syndrome with a germline mutation in the mismatch repair (MMR) genes. Microsatellite instability is found in most of these tumors, but it also appears in 15% to 20% of all sporadic colorectal cancers. Although the phenotype in both these cancers is the same, the genotype is different. In HNPCC tumors, MMR errors are due to an inherited mutation in the MMR gene, K-ras mutation is frequent, and most arise from villous adenomas. In sporadic colorectal cancers, MMR errors are due to epigenetic silencing of the MMR gene MLH1, the BRAF-V600E mutation is frequent, and most arise from the serrated-polyp pathway. This article reviews the genetic, clinical, and pathologic differences and similarities between these tumor types.
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