Summary

MSI or microsatellite instability testing is used to assess whether someone has the genetic mutations or variants that cause Lynch syndrome. Lynch syndrome is the most common inherited form of colon cancer accounting for about three per cent of cases. People with Lynch syndrome usually develop colon cancer at a younger age and if you have it, close family members are at greater risk. MSI testing is performed on a sample of a tumour or polyp taken during surgery. If you have a positive result, you will need to have a further genetic test through a blood test to confirm a diagnosis of Lynch syndrome.

Why get tested?

Lynch syndrome is due to variants in the genes that repair mistakes made when DNA is copied. DNA is present in almost all cells in the body, and it is copied whenever cells replace themselves. 

Genes that repair mutations in DNA are known as mismatch repair genes. They normally protect you from getting certain cancers.

There are four different mismatch repair genes that are responsible for correcting mutations. These genes are MLH1, MSH2, MSH6 and PMS2. If one of these four mismatch repair genes is mutated, small errors in the DNA are not corrected. These errors lead to an expansion or reduction in repetitive sequences in the DNA. This is known as microsatellite instability or MSI.

A physician or surgeon may request MSI testing if you have colorectal cancer at a relatively young age or if you have a family history of colorectal cancer or other tumours associated with Lynch syndrome. Lynch syndrome is associated with a higher risk of developing more than one colorectal cancer as well as an increased risk of developing cancers of the uterus, ovary, stomach, urinary tract, biliary tract, pancreas, small intestine, skin and brain.

When your sample is being investigated in the lab, the tissue pathologist may suggest MSI testing if the appearance of the tumour when viewed through a microscope is suggestive of Lynch syndrome.

How the tests work
There are two different types of tests that can look for defects in the mismatch repair genes. Both are performed on a biopsy of a cancerous polyp or from tissue taken during surgery for colon cancer. 

1. Microsatellite Instability (MSI) testing involves genetic testing of the tumour’s DNA to decide whether MSI is present. 
2. Immunohistochemical staining (IHC) involves staining the tissue samples and investigating it through a microscope. The staining can show up any absence of mismatch repair proteins. This indirectly reflects the presence of MSI. 

MSI testing has been largely replaced by IHC testing in many laboratories, but both tests may be used together in problematic cases.
 

Having the test

Sample 
A sample of the colon cancer tumour or a colon cancer polyp is removed at surgery.

Preparation
None
 

Your result

If MSI and/or IHC testing of the tumour suggests that Lynch syndrome is present a genetic test for mutations or variants in one of the mismatch repair genes is needed to confirm the diagnosis. This is a blood test.

It is important at this point that you are counselled in a genetic clinic before you do this, so that you understand the implications of having a positive, negative or inconclusive gene result. If a genetic variant is found in your DNA, a diagnosis of Lynch syndrome can be made.

Only 20 per cent of people with abnormal MSI or IHC results actually have Lynch syndrome. However, if a variant in a mismatch repair gene is confirmed through a genetic test you are at significantly high risk of developing cancers associated with Lynch syndrome.

People with Lynch syndrome have a 52 - 70 per cent risk of developing colorectal cancer in their lifetime, compared to a six per cent lifetime risk in the general population. Women with Lynch syndrome have a 25 - 71 per cent risk of developing cancer of the uterus, compared to a two to three per cent risk in women without Lynch syndrome.

Having a cancer-causing gene mutation does not always mean that someone will develop cancer. This is known as incomplete penetrance. This is a term used to describe why some people with disease-causing mutations in a gene develop cancer, while others with the same mutation do not. Incomplete penetrance is not fully understood but probably due to a combination of genetic, environmental and lifestyle factors.

If you test positive for Lynch syndrome the diagnosis will enable your doctors to monitor you to make sure any tumour you develop is caught at an early stage. Suggested surveillance measures include a colonoscopy every one to two years, gastroscopy every two years, and annual urine testing. If you are female, this also includes 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 you have completed your family.

If the genetic variant underlying Lynch syndrome is identified your relatives may be at risk of carrying the same genetic variant which would also predispose them to the cancers associated with Lynch syndrome. Your relatives are recommended to have genetic counselling about their options for testing.
 

More information

Pathology and diagnostic imaging reports can be added to your My Health Record. You and your healthcare provider can now access your results whenever and wherever needed.

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