There are two different types of tests which can look for defects in the mismatch repair genes. Both types of tests are performed on a biopsy of a cancerous polyp or from tissue taken during surgery for colon cancer. The first type of testing is called Microsatellite Instability (MSI) testing. This involves genetic testing of the tumour DNA to  determine whether MSI is present. The second type of testing is immunohistochemical staining (IHC) which is performed on samples of the colon cancer tumour to look for the absence of mismatch repair proteins. There are four mismatch repair proteins which can be tested with IHC. These four proteins are the products of the four mismatch repair genes (MLH1, MSH2, MSH6 and PMS2) associated with Lynch syndrome. If absent staining is found for one of the mismatch repair proteins, this indirectly reflects the presence of MSI and this may be due to a mutation in the corresponding gene which the person was born with. MSI testing has been largely replaced by IHC testing in many laboratories, but both tests may be used together in problematic cases. If MSI and/or IHC testing on the tumour is abnormal, a blood test would then be required to determine if a mutation in one of the mismatch repair genes is present. If a gene mutation is identified in the blood sample, the patient has Lynch syndrome and their relatives are also at risk. Their relatives would be recommended to have genetic counselling about their options for testing.

The physician or surgeon may request MSI testing in a patient with colorectal cancer who is less than 50 years old, or who has a family history of colorectal cancer at less than 50 years of age or of any other tumour associated with Lynch syndrome.

A pathologist may suggest MSI or IHC testing on a colon cancer tumour if the microscopic appearance of the tumour is suggestive of Lynch syndrome.

The result of MSI and/or IHC testing of the tumour may suggest that Lynch syndrome is present, but genetic testing for mutations in one of the mismatch repair genes is required to prove this. Only 20% of people with abnormal MSI or IHC results actually have Lynch syndrome. To explore the possibility of Lynch syndrome, a blood sample is collected from the patient and sent for mutation analysis of the mismatch repair genes.  The patient should be counselled in a Genetic Clinic prior to having a blood sample collected and sent for testing, so that they understand the implications of having a positive, negative or inconclusive gene result. If a gene mutation is found in the blood, a diagnosis of Lynch syndrome can be made.

Lynch syndrome is associated with a higher risk of developing more than one colorectal cancer. It is also associated with an increased risk of developing cancers of the uterus, ovary, stomach, urinary tract, biliary tract, pancreas, small intestine, skin and brain. If the gene mutation underlying Lynch syndrome is identified in an individual, their relatives may be at risk of carrying the same gene mutation which would also predispose them to the cancers associated with Lynch syndrome. Other family members can be referred to a Genetic Clinic to discuss their risks and they can be tested for the gene mutation which has been identified in their relative, if they wish.

The detection of a mutation in a mismatch repair gene in the blood of an individual confirms the diagnosis of Lynch syndrome. Making this diagnosis allows for close surveillance of the affected individual to detect possible tumour development at an early stage. Suggested surveillance measures include a colonoscopy every one to two years, gastroscopy every two years, annual urine testing and referral to a gynaecologist for annual ultrasound scan of the uterus and consideration for prophylactic surgical removal of the uterus, fallopian tubes and ovaries once an affected woman has completed her family.

Most people with MSI-positive tumours do not have Lynch syndrome. However, if a mutation in a mismatch repair gene has been detected in the blood of the individual, the patient is at significantly high risk of developing cancers associated with Lynch syndrome. Patients with Lynch syndrome have a 52-70% risk of developing colorectal cancer in their lifetime, compared to a 6% lifetime risk in the general population. Women with Lynch syndrome have a 25-71% risk of developing cancer of the uterus, compared to a 2 – 3% risk in women without Lynch syndrome.

The test is requested by a registered medical practitioner if they consider it appropriate. Genetic counselling is recommended if the MSI or IHC results on the tumour suggest a defect in the mismatch repair genes. The Genetic Counselling clinic can assess the patient and determine if a blood test to check for mutations in the relevant mismatch repair gene(s) is indicated.