Lynch syndrome testing: tumour tests, genetic tests and what results mean

East Genomics describes Lynch syndrome as a rare condition that can run in families and can lead to a higher risk of certain cancers, including those of the bowel, womb (endometrium), stomach and pancreas. It is the most common cause of hereditary colorectal cancer. People with Lynch syndrome are more likely to get colorectal cancer and other cancers, including endometrial, stomach, liver, kidney, brain and certain skin cancers, and at a younger age, often before 50.

RM Partners explains that in most people colorectal and endometrial cancers are not inherited. In about 5 to 10 in 100 of those who develop colorectal or endometrial cancer the cancer is caused by a genetic alteration, and in about 3 in 100 the genes affected are DNA mismatch repair genes, which protect against certain cancers by repairing errors when cells are made. That is the situation in Lynch syndrome, which affects 1 in 278 people.

In the UK, testing is built into the care of people diagnosed with bowel or womb cancer. East Genomics notes that NICE has recommended Lynch syndrome testing for people with colorectal cancer since 2017 using immunohistochemistry (IHC) or microsatellite instability (MSI) testing, and since October 2020 for people diagnosed with endometrial cancer using IHC. RM Partners says that every person diagnosed with colorectal or endometrial cancer has IHC performed on their tumour.

The aim is to find the small proportion of cancers caused by Lynch syndrome. East Genomics says that around 95% of people in the UK who have Lynch syndrome have not been identified through testing and so cannot enter monitoring or treatment. Identifying them means they can be monitored from a younger age, tumours could be caught sooner and treatment could be more effective.

RM Partners describes the initial tumour tests as follows. Because they are done on tissue already removed or biopsied, you do not need a separate procedure for them.

• Immunohistochemistry (IHC) looks at the expression of the proteins produced by the mismatch repair genes. If there is a loss of expression of any of these proteins, you may be offered genetic testing to find out whether you have Lynch syndrome.

• Microsatellite instability (MSI) testing is another test on the tumour to find out whether you are likely to have Lynch syndrome. RM Partners says it is only used for colorectal cancer, and that a positive result means you might have Lynch syndrome and will be offered genetic testing.

• MLH1 promoter hypermethylation may be used after an IHC test in some cases. If the tumour sample is methylated, that clarifies that the cancer is sporadic and arose in the tumour cells. If it is not, it is possible that you might have Lynch syndrome and you will be offered genetic testing.

If the tumour tests show that there is a possibility of Lynch syndrome, you will be offered genetic testing, which RM Partners says can confirm whether you have it. East Genomics adds that if both IHC or MSI and MLH1 tests show a person may have Lynch syndrome, genetic testing of the person's non-tumour DNA should be done to confirm it. In practice that is a blood sample analysed by a genetics laboratory, and you are usually offered an appointment with a genetics service to discuss it.

People who were diagnosed with bowel or womb cancer in the past and were never tested can ask their GP or cancer team whether a referral to a genetics service is appropriate, taking account of their personal and family history of cancer.

A confirmed Lynch syndrome result means a pathogenic variant has been found in one of the mismatch repair genes. It matters for you, because preventative treatment and screening are available, and for relatives, who can be offered testing for the same variant. Because it is inherited, close relatives each have a chance of carrying the same variant, and the genetics team will explain this and help you talk to your family.

If the tumour tests were abnormal but no gene variant was found, or the MLH1 methylation result shows a sporadic cancer, the diagnosis of Lynch syndrome is not made. That does not mean the family history is irrelevant, and your genetics team may still advise on the family's cancer risk and any extra screening based on the history. Ask the team to explain precisely which category your result falls into.

East Genomics says there are new Lynch syndrome expert networks in the East Midlands and East of England providing multidisciplinary care, with preventative treatment and screening for patients and at-risk relatives. Care is arranged through genetics and cancer services, and details vary by region. The charities Lynch Syndrome UK, Macmillan Cancer Support, Bowel Cancer UK and the Eve Appeal provide patient information.

Emotional reactions to a result vary, and genetics services usually offer counselling. Speak to the genetics team about how to share the result with relatives, including those who are younger and may be offered testing.