NICE Issues Diagnostics Guidance on Molecular Testing Strategies for Lynch Syndrome in Patients with Colorectal Cancer

Evidence-based recommendations on using immunohistochemistry or microsatellite instability testing to guide further testing for Lynch syndrome

In February 2017, NICE published evidence-based recommendations on using immunohistochemistry or microsatellite instability testing to guide further testing for Lynch syndrome in patients with colorectal cancer. The recommendations consider offering testing to all patients 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. The guidance emphasizes: Do not wait for the results before starting treatment.

Steps in the immunohistochemistry testing strategy

Step 1: Do an immunohistochemistry 4‑panel test for MLH1, MSH2, MSH6 and PMS2.

Step 2: 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.

Step 3: If the BRAF V600E test is negative, do an MLH1 promoter hypermethylation test.

Step 4: If the MLH1 promoter hypermethylation test is negative, confirm Lynch syndrome by genetic testing of germline DNA.

In term of steps 2-4, if the MSH2, MSH6 or PMS2 immunohistochemistry results are abnormal, confirm Lynch syndrome by genetic testing of germline DNA.

Steps in the microsatellite instability testing strategy

Step 1: Do a microsatellite instability test.

Step 2: 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.

Step 3: If the BRAF V600E test is negative, do an MLH1 promoter hypermethylation test.

Step 4: If the MLH1 promoter hypermethylation test is negative, confirm Lynch syndrome by genetic testing of germline DNA.

Healthcare professionals should ensure that patients 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.

About clinical need and practice, the diagnostic tests, evidence, committee discussion and implementation of this guidance you can find more here