Low density of FOXP3-positive T cells in normal colonic mucosa is related to the presence of beta2-microglobulin mutations in Lynch syndrome-associated colorectal cancer.

Microsatellite instability (MSI-H) is caused by DNA mismatch repair deficiency and occurs in 15% of colorectal cancers. MSI-H cancers generate highly immunogenic frameshift peptide (FSP) antigens, which elicit pronounced local immune responses. A subset of MSI-H colorectal cancers develops in frame of Lynch syndrome, which represents an ideal human model for studying the concept of immunoediting.

Mismatch repair-deficient crypt foci in Lynch syndrome--molecular alterations and association with clinical parameters.

Lynch syndrome is caused by germline mutations of DNA mismatch repair (MMR) genes, most frequently MLH1 and MSH2. Recently, MMR-deficient crypt foci (MMR-DCF) have been identified as a novel lesion which occurs at high frequency in the intestinal mucosa from Lynch syndrome mutation carriers, but very rarely progress to cancer. To shed light on molecular alterations and clinical associations of MMR-DCF, we systematically searched the intestinal mucosa from Lynch syndrome patients for MMR-DCF by immunohistochemistry.

Clinical significance of microsatellite instability in colorectal cancer.

Introduction: Colorectal cancer is a heterogeneous tumor type with regard to molecular pathogenesis and genetic instability. The majority of colorectal cancers display chromosomal instability and follow the classical adenoma-carcinoma sequence of tumor progression. A subset of about 15 % of colorectal cancers, however, displays DNA mismatch repair (MMR) deficiency and the high-level microsatellite instability (MSI-H) phenotype.