Molecular testing strategies for Lynch syndrome in people with colorectal cancer

3 Current practice

Testing strategies for Lynch syndrome in people with colorectal cancer (CRC) varies widely (estimated 50% of centres currently providing tests) and some trusts still need to establish a strategy within their service. Contributors to this resource reported that the criteria commonly used to identify people to test include a diagnosis of CRC in people aged under 50 years and a strong family or personal history according to the Bethesda and Amsterdam criteria. Reasons for using such criteria, as stated by contributors to this resource, include alignment with the Royal College of Pathology dataset for CRC histopathology reports, prevention of unnecessary testing and the likelihood of having Lynch syndrome.

Four out of the 5 trusts that helped to develop this document use immunohistochemistry (IHC) testing as the first test to identify tumours with mismatch repair (MMR) deficiency. This can be carried out in local histopathology laboratories. The other trust uses microsatellite instability (MSI) testing as the first test. This test is usually carried out in accredited specialist clinical laboratories.

If the IHC result is abnormal or the MSI result is positive referral to clinical genetics may be needed. Further sequential tests are likely to be requested by clinical genetics, and done at specialist clinical laboratories. Systems must be in place to request sequential tests, transport samples (either tumour tissue for BRAF and MLH1 hypermethylation tests or blood for genetic testing of germline DNA), and to follow-up results. Because of the challenges in setting up robust systems, even those trusts that have a testing strategy do not consistently refer people who need further sequential tests to clinical genetics services to either confirm or rule out Lynch syndrome.