How is Lynch syndrome diagnosed?

Screening tests and genetic testing are used to diagnose Lynch syndrome. A biopsy of the tumor is used for two screening tests. One test looks for changes that indicate the gene that affects DNA repairs is not working. These changes are called microsatellite instability or MSI. Tumors that have microsatellite instability are called MSI-high (MSI-H). Some 90 to 95 percent of colorectal cancers (and many endometrial cancers) from individuals with Lynch syndrome are MSI-H. This means that the cancer in the family is likely due to Lynch syndrome. However, since about 5 to 10 percent of Lynch syndrome tumors do not show instability, a negative MSI-H test cannot completely rule out the possibility of a Lynch syndrome diagnosis.

There is a second type of screening test for Lynch syndrome that uses a technique called immunohistochemistry (IHC). IHC testing is a screening test done on the tumor that looks for the expression of Lynch syndrome gene products (proteins). If one or more of the proteins are missing in the tumor, it suggests that there is a mutation in that gene, which could then be found through genetic testing. Approximately 88 percent of individuals with Lynch syndrome will have an abnormal IHC result.

Ideally, MSI and/or IHC testing should be done before genetic testing is ordered. However, there are occasions where MSI or IHC cannot be done, in which case genetic testing can be performed. Genetic counseling is recommended before ordering genetic testing. Genetic testing, which involves a blood draw or obtaining a brushing from the inside of the mouth (buccal swab), helps determine if a MLH1, MSH2, MSH6, PMS2, or EPCAM gene mutation is present in the family.

If genetic testing reveals a mutation, a diagnosis of Lynch syndrome is confirmed. Other family members can then be tested. Any other family members who have a mutation would also be at an increased risk for developing cancers associated with Lynch syndrome and should be monitored. If no mutation is found, Lynch syndrome is not necessarily excluded. A genetic counselor can further discuss the meaning of negative genetic test results and cancer risk.

How is Lynch syndrome inherited?

Lynch syndrome is an autosomal dominant disorder. This means that if only one parent carries the mutation for Lynch syndrome, there’s a 50 percent chance a child of the parents will inherit the mutation.

Individuals diagnosed with Lynch syndrome should tell their family members and encourage them to undergo genetic counseling. Counseling includes an evaluation of their personal and family history as well as and genetic testing for the Lynch syndrome gene mutation.

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