Microsatellite instability (MSI)

The tests for MSI use immunohistochemical stains on samples of the colon cancer tumour removed at surgery to look for abnormal proteins resulting from mutations of one or more of the four mismatch repair genes associated with Lynch syndrome (MLH1, MSH2, MSH6 and PMS2). If an abnormal staining pattern is found, this is highly suggestive of microsatellite instability and a sample of the tumour will be referred for genetic testing to look for the specific gene mutation in that patient.

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 perform immunohistochemistry for MSI on a colon cancer tumour if the microscopic appearance of the tumour is suggestive of Lynch syndrome.

The result of immunohistochemical staining of the tumour may suggest that Lynch syndrome is present, but requires further genetic testing to prove this. The patient will be counselled prior to having a blood sample collected and sent for analysis of the possible gene mutations associated with Lynch syndrome. If a gene mutation is found, 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. A MSI positive result means that there is a high probability of one or more close family members of the patient carrying the faulty gene(s) which would predispose them to developing these cancers.

Early detection of the mutation and hence diagnosis of Lynch syndrome 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 of the uterus and consideration for a prophylactic surgical removal of the uterus, fallopian tubes and ovaries once an affected woman has completed her family.