Diagnosing Lynch Syndrome

Lynch syndrome dramatically increases the risk for cancer in a person’s lifetime. The genetic condition can have a significant impact on individuals and families—resulting in early onset cancer, multiple cancers, and many generations of a family affected by cancer. As such, it is important to diagnose and manage Lynch syndrome in order to prevent cancer or detect it early when it is most treatable.

The Importance of Diagnosing Lynch Syndrome

Lynch syndrome has a variety of implications for individuals and families. Individuals who have Lynch syndrome have a much higher risk of developing colorectal, uterine, and other cancers than the general population. Furthermore, individuals with Lynch syndrome who already have cancer have a higher risk of developing new cancers in the future. What’s more—because Lynch syndrome is an inherited condition, it can affect other family members. A diagnosis of Lynch syndrome can shine the light on potentially increased risk throughout a family.

Signs of Lynch Syndrome

There are some common features in families with Lynch syndrome and these are sometimes referred to as the Amsterdam II criteria:

1. Three or more relatives have colorectal, uterine, or another Lynch-associated cancer, one of whom is a first-degree relative of the others

2. Two or more successive generations have cancer

3. One or more relative was diagnosed before the age of 50
(Familial adenomatous polyposis (FAP) has been excluded)

The Amsterdam II criteria is simply a starting point for developing suspicion of Lynch syndrome, but it is an imperfect tool for making a clear diagnosis. Some families meet the Amsterdam II criteria, but do not have Lynch syndrome; other families do not meet the criteria, but do have Lynch syndrome.

The National Cancer Institute (NCI) has released a set of recommendations called the Bethesda Guidelines to help identify individuals who may benefit from undergoing initial testing for Lynch syndrome. Some research indicates that the Bethesda guidelines might be more sensitive than the Amsterdam II Criteria in detecting families at risk for Lynch syndrome. The most recent version of the guidelines, published in 2004 are as follows:

-One relative diagnosed with colorectal cancer prior to age 50

-Presence of any synchronous (at the same time) or metachronous (at another time) Lynch-associated tumors, regardless of age

-Colorectal cancer with high microsatellite instability histology diagnosed in a patient under the age of 60

-Colorectal cancer diagnosed in one or more first-degree relatives with a Lynch-associated tumor, with one of those cancer diagnosed before age 50

-Colorectal cancer diagnosed in two or more first-degree or second-degree relatives with Lynch-associated tumors, regardless of age.

Diagnosing Lynch Syndrome

There is a process to diagnosing Lynch syndrome and it typically begins with a comprehensive review of the family medical history, which is sometimes followed by genetic testing.

Family History: A genetic counselor will construct a multi-generational family tree and perform a comprehensive review of a family medical history in order to assess a family’s risk of Lynch syndrome. If the family history indicates the possibility of Lynch syndrome, the counselor might suggest further tests. To find a genetic counselor in your area refer to our How to Find a Genetic Counselor page.

Testing: There are two types of tests used for detecting Lynch syndrome—pathology tests and genetic blood tests.

Pathology tests are tests that are performed on a tumor. When tumors are removed, most hospitals store tissue samples for many years. If Lynch syndrome is suspected, special pathology tests can be used to detect characteristics in tumors that may be caused by Lynch syndrome and can identify which gene may be responsible for Lynch syndrome in the family. There are two pathology tests used to evaluate the possibility of Lynch syndrome:

-Microsatellite instability (MSI) testing: Microsatellites are sequences of cellular DNA. In people with Lynch syndrome, tumors will show changes in the microsatellites and these changes are called microsatellite instability or MSI. Tumors with this instability are referred to as MSI-positive. Approximately 95 percent of colorectal and uterine cancers in Lynch syndrome patients are MSI-positive.

-Immunohistochemistry (IHC) testing: Immunohistochemistry testing uses special dyes to stain tissue samples in order to determine whether the proteins made by the Lynch syndrome genes are present or absent. In patients with a Lynch syndrome gene mutation, the protein will be absent in the tumor. IHC testing can help identify which of the four Lynch syndrome genes to test for.

The results of IHC or MSI tests can indicate that Lynch syndrome might be present, but they don’t provide definitive information because some people can develop these gene mutations only in their cancer cells. The suspicion of Lynch syndrome will be confirmed by blood tests.

Genetic tests are tests that look for changes in your genes that indicate that you have Lynch syndrome. In order to undergo genetic testing, you will need to provide a blood sample. Genetic professionals will then perform a special laboratory analysis on your blood to look at specific gene mutations that cause Lynch syndrome.

Next Section: Managing Lynch Syndrome»