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Background Microsatellite instability (MSI) is a key marker for predicting the response of immune checkpoint inhibitors (ICIs) and for screening Lynch syndrome (LS). Aim This study aimed to see the characteristics of cancers with high level of MSI (MSI-H) in genetic medicine and precision medicine. Methods This study analyzed the incidence of MSI-H in 1000 cancers and compared according to several clinical and demographic factors. Results The incidence of MSI-H was highest in endometrial cancers (26.7%, 20/75), followed by small intestine (20%, 3/15) and colorectal cancers (CRCs)(13.7%, 64/466); the sum of these three cancers (15.6%) was significantly higher than that of other types (2.5%)( P  &lt; 0.0001). MSI-H was associated with LS-related cancers ( P  &lt; 0.0001), younger age ( P  = 0.009), and family history, but not with smoking, drinking, or serum hepatitis virus markers. In CRC cases, MSI-H was significantly associated with a family history of LS-related cancer ( P  &lt; 0.0001), Amsterdam II criteria [odds ratio (OR): 5.96], right side CRCs (OR: 4.89), and multiplicity (OR: 3.31). However, MSI-H was very rare in pancreatic (0.6%, 1/162) and biliary cancers (1.6%, 1/64) and was null in 25 familial pancreatic cancers. MSI-H was more recognized in cancers analyzed for genetic counseling (33.3%) than in those for ICI companion diagnostics (3.1%)( P  &lt; 0.0001). Even in CRCs, MSI-H was limited to 3.3% when analyzed for drug use. Conclusions MSI-H was predominantly recognized in LS-related cancer cases with specific family histories and younger age. MSI-H was limited to a small proportion in precision medicine especially for non-LS-related cancer cases.

bmc cancer

Microsatellite instability is biased in Amsterdam II-defined Lynch-related cancer cases with family history but is rare in other cancers: a summary of 1000 analyses