Genetic Evaluation and Management of Lynch Syndrome

Testing for MMR deficiency of newly diagnosed CRC should be performed. This can be done for all CRCs, or CRC diagnosed at age 70 years or younger, and in individuals older than 70 years who have a family history concerning for LS. Analysis can be done by IHC testing for the MLH1 / MSH2 / MSH6 / PMS2 proteins and / or testing for MSI. Tumors that demonstrate loss of MLH1 should undergo BRAF testing or analysis of MLH1 promoter hypermethylation. To facilitate surgical planning, tumor testing on suspected CRC should be performed on preoperative biopsy specimens, if possible. (III, B)

Individuals who have a personal history of a tumor showing evidence of MMR deficiency (without evidence of MLH1 promoter methylation); uterine cancer diagnosed at younger than age 50 years; a known family MMR gene mutation; fulfill Amsterdam criteria or revised Bethesda guidelines; and / or have a personal risk of ≥5 % chance of LS based on prediction models should undergo genetic evaluation for LS. (III, B)