Tools and resources

1 Introduction

1 Introduction

This resource has been developed to provide practical information and advice on NICE diagnostics guidance on molecular testing strategies for Lynch syndrome in people with colorectal cancer (CRC).

NICE's adoption team worked with contributors who use molecular testing strategies in NHS trusts to gather learning and experiences.

The purpose of this resource is to support the NHS in adopting and evaluating the impact of adopting these testing strategies as part of a specialist service. It is aimed at providers and commissioners of colorectal cancer services, clinical genetics services and laboratories responsible for doing the molecular tests. It is complementary to the guidance and was not considered by the diagnostics advisory committee when developing its recommendations.

Lynch syndrome is an inherited predisposition to some cancers, including CRC. People with Lynch syndrome also have an increased risk of other cancers, such as endometrial, ovarian, stomach, small intestine, hepatobiliary tract, urinary tract, brain and skin cancer. This is caused by mutations in mismatch repair (MMR) genes which normally correct mistakes when DNA is being replicated. In a person with Lynch syndrome, these mismatch errors happen more often which may result in the development of cancer.

Offering testing of colorectal tumours after surgical resection or biopsy using either microsatellite instability (MSI) or immunohistochemistry (IHC) testing for MMR deficiency can be used to screen for people in whom the cancer may have occurred because of Lynch syndrome. MSI testing is usually carried out in accredited specialist clinical laboratories. The tissue specimens are first assessed by a histopathologist or a molecular pathologist (within molecular or molecular genetic laboratories, or a local histopathology laboratory), who marks out the tumour areas in the tissue and determines the neoplastic cell content. IHC testing can be done in local histopathology laboratories. Further sequential testing for those tumours with a positive MSI result or an abnormal IHC result is needed to make a Lynch syndrome diagnosis. This is usually done in specialist clinical laboratories, although some of these further tests may take place in local laboratories. Further testing includes BRAF V600E and MLH1 promoter hypermethylation (both carried out on tumour tissue) but the final diagnosis, if a negative result is received for these tests, can only be confirmed after genetic testing of germline DNA (carried out on a blood sample).


The benefits of using molecular testing strategies as reported by the NHS staff involved in producing this resource may include:

  • Earlier identification of people with Lynch syndrome.

  • A more consistent patient pathway to identify all people with CRC who also have Lynch syndrome.

  • Reassurance for patients and relatives when testing rules out a diagnosis of Lynch syndrome.

  • Prevention or early detection of some of the other types of cancers which people with Lynch syndrome are at higher risk of, through earlier surveillance and preventive treatment.

  • Cascade genetic testing of relatives after a positive diagnosis of Lynch syndrome. Identifying other family members with Lynch syndrome will prompt earlier colonoscopy for detecting CRC and other cancer screening, as well as preventive treatment with aspirin. Both of these interventions significantly reduce the risk of developing CRC.

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