Understanding Genetic Screening

Has your healthcare professional told you or a family member that your family meets the screening guidelines called Amsterdam II or Bethesda Guidelines for Lynch Syndrome? If so, the provider may have suggested a member of your family undergo genetic screening. Genetic screening is different from genetic testing.

If you or a family member have been recommended to have formal genetic testing, you should speak with a genetic counselor for detailed information. They will guide you through the process so it does not become overwhelming. You can find additional information on genetic screening below.

Our bodies are made up of many genes, some of which can become abnormal. Mismatch repair (MMR) genes fix mistakes made during DNA replication which prevents cancer development. When MMR genes stop working properly, the mistakes add up and result in cancer formation.

Common Genetic Screening Tests:

In addition to blood and saliva testing, the following screening tests can be done on tumor specimens.

Microsatellite Instability (MSI) Testing

• This screening can be done on a biopsy sample or a surgical tumor specimen. This is done by using tumor tissue to make slides. The slides can be looked at under a microscope. This test can even be done on a previously removed specimen if the hosptial where the operation was done still has the slides.  

• This test evaluates the tumor tissue for areas of repetitive errors in DNA replication sequences.
• The results are classified as high or low instability based on the amount of repetitive areas found in the tumor tissue.
• Approximately 90% of Lynch Syndrome cancers are MSI positive compared to 15% of sporadic colorectal cancer malignancies

Immunohistochemistry (IHC)

• This screening can be done on a surgical tumor specimen and evaluates tumor tissue for loss of mismatch repair (MMR) proteins.
• It is fast, inexpensive, and requires a small amount of tissue.
• This test can help determine specific genes to target if your family is referred for formal genetic testing.

MSI or IHC can be done separately or together. This decision will be made by your healthcare professional and typically varies by institution.  

MMR Genes

• MSH2 is the most commonly mutated gene. MLH1, MSH6, PMS2, and EPCAM can also be mutated in Lynch Syndrome.

The results of your genetic screening can be complex to understand. You should make an appointment with your healthcare provider and/or genetic counselor to discuss and interpret the results. Knowing if you carry a genetic mutation associated with Lynch Syndrome can ensure you receive close interval surveillance for Lynch Syndrome related malignancies.

References

Gibson, J., Lacy, J., Matloff, E., & Robert, M. (2014). Microsatellite instability testing in colorectal carcinoma: a practical guide. Clinical Gastroenterology and Hepatology, 12(2),     171-176.e1. Advance online publication. doi: 10.1016/j.cgh.2013.11.001.

Strafford, J. C. (2012). Genetic testing for lynch syndrome, an inherited cancer of the bowel, endometrium, and ovary. Reviews in Obstetrics & Gynecology,  (1), 42-49. PMCID: PMC3349923