Hereditary nonpolyposis colorectal cancer screening

Screening strategy for colon cancer patients
Genetic testing for mutations in DNA mismatch repair genes is expensive and time-consuming, so researchers have proposed techniques for identifying cancer patients who are most likely to be HNPCC carriers as ideal candidates for genetic testing. The Amsterdam Criteria (see below) are useful, but do not identify up to 30% of potential Lynch syndrome carriers. In colon cancer patients, pathologists can measure microsatellite instability in colon tumor specimens, which is a surrogate marker for DNA mismatch repair gene dysfunction. If there is microsatellite instability identified, there is a higher likelihood for a Lynch syndrome diagnosis. Recently, researchers combined microsatellite instability (MSI) profiling and immunohistochemistry testing for DNA mismatch repair gene]] expression and identified an extra 32% of Lynch syndrome carriers who would have been missed on MSI profiling alone. Currently, this combined immunohistochemistry and MSI profiling strategy is the most advanced way of identifying candidates for genetic testing for the Lynch syndrome.

Genetic counseling and genetic testing are recommended for families that meet the Amsterdam criteria, preferably before the onset of colon cancer.

Amsterdam criteria
The following are the Amsterdam criteria in identifying high-risk candidates for molecular genetic testing:

Amsterdam Criteria:
 * Three or more family members with a confirmed diagnosis of colorectal cancer, one of whom is a first degree (parent, child, sibling) relative of the other two
 * Two successive affected generations
 * One or more colon cancers diagnosed under age 50 years
 * Familial adenomatous polyposis (FAP) has been excluded

Amsterdam Criteria II:
 * Three or more family members with HNPCC-related cancers 3, one of whom is a first degree relative of the other two
 * Two successive affected generations
 * One or more of the HNPCC-related cancers diagnosed under age 50 years
 * Familial adenomatous polyposis (FAP) has been excluded