Offer testing to all people with colorectal cancer, when first diagnosed, using immunohistochemistry for mismatch repair proteins or microsatellite instability testing to identify tumours with deficient DNA mismatch repair, and to guide further sequential testing for Lynch syndrome (see 1.2 and 1.3). Do not wait for the results before starting treatment.
If using immunohistochemistry, follow these steps:
Do an immunohistochemistry 4‑panel test for MLH1, MSH2, MSH6 and PMS2.
If the MLH1 immunohistochemistry result is abnormal, use sequential BRAF V600E and MLH1 promoter hypermethylation testing to differentiate sporadic and Lynch syndrome-associated colorectal cancers. First do a BRAF V600E test. If the MSH2, MSH6 or PMS2 immunohistochemistry results are abnormal, confirm Lynch syndrome by genetic testing of germline DNA.
If the BRAF V600E test is negative, do an MLH1 promoter hypermethylation test. If the MSH2, MSH6 or PMS2 immunohistochemistry results are abnormal, confirm Lynch syndrome by genetic testing of germline DNA.
If the MLH1 promoter hypermethylation test is negative, confirm Lynch syndrome by genetic testing of germline DNA. If the MSH2, MSH6 or PMS2 immunohistochemistry results are abnormal, confirm Lynch syndrome by genetic testing of germline DNA.
If using microsatellite instability testing, follow these steps:
Do a microsatellite instability test.
If the microsatellite instability test result is positive, use sequential BRAF V600E and MLH1 promoter hypermethylation testing to differentiate sporadic and Lynch syndrome-associated colorectal cancers. First do a BRAF V600E test.
If the BRAF V600E test is negative, do an MLH1 promoter hypermethylation test.
If the MLH1 promoter hypermethylation test is negative, confirm Lynch syndrome by genetic testing of germline DNA.
Healthcare professionals should ensure that people are informed of the possible implications of test results for both themselves and their relatives, and ensure that relevant support and information is available. Discussion of genetic testing should be done by a healthcare professional with appropriate training.
Laboratories doing microsatellite instability testing or immunohistochemistry for mismatch repair proteins should take part in a recognised external quality assurance programme.