Lynch Syndrome/Hereditary Non-Polyposis Colon Cancer – HNPCC
Lynch syndrome, also called hereditary non-polyposis colon cancer (HNPCC), is characterized by an increased risk of colon cancer and other cancers (e.g., of the endometrium, ovary, stomach, small intestine, hepatobiliary tract, upper urinary tract, brain, and skin). Lynch syndrome is inherited in an autosomal dominant manner and it is associated with germline mutations in the mismatch repair (MMR) genes MLH1, MSH2, MSH6 and PMS2. Mutation carriers have a lifetime risk of up to 80% for colorectal cancer, 20-60% risk of endometrial cancer, as well as other tumors. Lynch syndrome is associated with early onset of cancer, the average age of diagnosis is 45 years.
Referral for molecular testing of Lynch syndrome:
- Tumour tissue analysis to evaluate the MMR proteins expression by immunohistochemical analysis (IHC) and DNA microsatellite instability (MSI) testing is suggested for the individuals meeting Amsterdam II/Bethesda criteria.
- If absence of the MLH1/PMS2 proteins expression is observed by IHC, methylation analysis of the MLH1 gene promoter and/or testing of the somatic BRAF V600E mutation is recommended in order to exclude sporadic colorectal cancer cases.
- If tumour with MMR deficiency and MSI high is detected, further mutation analysis from peripheral blood/normal tissue of the MMR genes is indicated.
Indications for mutation analysis:
- Testing of individuals meeting Amsterdam II/Bethesda criteria
- Testing of individuals with family history of colorectal cancer or other Lynch syndrome-related cancers
- Testing of at-risk family members for known mutations
- Genetic counseling