If IHC is abnormal with loss of MLH1, or loss of both MLH1 and PMS2 protein expression, do MLH1 promoter hypermethylation testing of tumour DNA. If MLH1 promoter hypermethylation is not detected, offer germline genetic testing to confirm Lynch syndrome.
If IHC is abnormal with loss of MSH2, MSH6 or isolated PMS2 protein expression, offer germline genetic testing to confirm Lynch syndrome.
1.2 Healthcare professionals should inform people about the possible implications of test results for both themselves and their relatives, and give support and information. Discussion of genetic testing and obtaining consent should be done by a healthcare professional with appropriate training.
1.3 Laboratories doing IHC for MMR proteins, MLH1 promoter hypermethylation testing or germline genetic testing should take part in a recognised external quality assurance programme.
Why the committee made these recommendations
Lynch syndrome is an inherited condition that increases the risk of certain types of cancer, including endometrial and colorectal cancer. NICE recommends testing for Lynch syndrome after a colorectal cancer diagnosis. But endometrial cancer is often the first cancer that people with Lynch syndrome will have. So, Lynch syndrome could be identified earlier if tests are done after a diagnosis of endometrial cancer.
If Lynch syndrome is diagnosed, treatment and surveillance can be offered to reduce the risk of having another Lynch syndrome-associated cancer (in particular colorectal cancer) or identify it earlier. Genetic testing for Lynch syndrome can also be offered to relatives with the aim of preventing Lynch syndrome-associated cancer developing or detecting it at an early stage.
Several types of tests can be done in different orders and combinations to see if endometrial cancer is likely to have been caused by Lynch syndrome. Economic modelling has shown that IHC testing then MLH1 promoter testing is likely to be the most cost-effective approach. If both these tests show that a person may have Lynch syndrome, genetic testing of a person's non-tumour DNA should be done to confirm this.
It is important that support and information are available for people deciding to be tested for Lynch syndrome.