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Molecular Genetic Testing

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Molecular Testing and Endometrial Cancer 

The role of genetic testing in endometrial cancer is growing. Genetic testing helps to personalize cancer therapies and also understand family cancer risk. It is a broad term to describe both testing patients for inherited cancer risk as well as testing the tumor itself for genetic mutations. 

Direct testing of the tumor is called somatic gene testing.  Testing of your DNA to see if there is an inherited genetic difference is called germline testing.  Some aspects of genetic testing are part of standard of care, others are used in certain circumstances. We will get into the details below. 


Somatic testing is testing of the tumor itself and this can occur in a few different ways. 


One type of tumor testing is called immunohistochemistry chemistry testing or IHC - this is a staining process that stains for certain proteins in the tumor, and can tell your doctor if you have certain mutations in the tumor or in your entire body that may have predisposed you to developing this cancer. IHC is now the standard of care for everyone diagnosed with endometrial cancer. It is done when your surgery or endometrial biopsy is first done and takes usually less than 1 week. This helps your doctor to determine two things: 


First - It will help your doctor determine if your cancer is caused by an inherited condition called Lynch Syndrome. If your proteins are abnormal, your doctor may recommend you undergo germline testing (a blood or saliva test) to see if you have those same genetic differences in all your cells. 


Second - It will help your doctor determine if your cancer is more susceptible to certain therapies, specifically immunotherapy. Patients with missing proteins have what is called ‚Äėmicrosatellite instability‚Äô and tend to respond well to immunotherapy. Immunotherapy is generally used if your cancer does not completely go away with surgery, radiation and chemotherapy, or if it comes back.¬†

IHC testing is standard of care for all patients with endometrial cancer when they are first diagnosed.

Make sure you ask your doctor what your test showed - if there were any abnormalities you will need follow up tests. 

Another type of tumor testing is called ‚Äúnext generation sequencing‚ÄĚ or ‚Äúmolecular sequencing.‚ÄĚ This compares the DNA mutations in your tumor to a panel of known endometrial cancer mutations in a database. This is sometimes performed at your hospital or sent out to special molecular sequencing company. Your doctor gets a printed report of genes that are mutated in your tumor. This can be helpful in two instances:¬†


First - it is recommended this be done for all patients with relapsed (recurrent) endometrial cancers. Depending on the mutations that are found in your tumor, you may be eligible for special targeted drugs that work best in tumors with a specific mutation. It can also be helpful to see if you are eligible for clinical trials that are exploring the use of certain drugs for patients with specific mutations. 


Second - For some patients, it can be helpful to have this information when you are first diagnosed, especially if your tumor is ‚Äėintermediate‚Äô risk and your doctor is trying to decide what therapies will be best for you after your initial surgery (radiation alone vs chemotherapy and radiation). Sometimes, for advanced stage or aggressive cancers, it can be good to have this information early so that if your cancer does not respond well to initial therapy, you can more easily get on a clinical trial or start a targeted drug.¬†¬†


Ask your doctor when you should have next generation sequencing or molecular sequencing and what this would mean for your cancer treatment. 



Some endometrial cancers (5-15%) develop from inherited genetic differences, meaning that families can pass down genes from generation to generation that increase the risk of developing endometrial cancer, colon cancer, ovarian cancers, and other cancers. 


Germline testing is done by sampling DNA through a cheek swab or by a blood sample. It is recommended for patients who have abnormalities in their IHC staining (as above) of their tumors. It is also recommended for patients who have several members of their family who have related cancers such as endometrial, colon and ovarian cancer. 


Lynch Syndrome 


One of the most common inherited forms of endometrial cancer comes from Lynch syndrome. Families affected by Lynch syndrome often are more likely to develop colon cancer, endometrial cancer, or ovarian cancer. Lynch syndrome is the cause of 3% of all endometrial cancers, and 9% of endometrial cancers in people under 50 years old.  Lynch syndrome is caused by genetic mutations that affect proteins that help to repair DNA.


How do I know if I am at risk for Lynch Syndrome? 

Talk to your doctor about your family medical history. If you have endometrial cancer - your tumor will be screened for Lynch Syndrome with IHC testing (as above) and you may need to have a confirmatory saliva or blood test. If you do not have endometrial cancer, your primary care doctor or gynecologist should be asking you annually about family cancer histories. If you have several family members with colon, endometrial, or ovarian cancers, you likely meet criteria for germline genetic testing. 


What if I have tested positive for Lynch syndrome? 

You will need screenings for the associated cancers - this includes colonoscopies, endometrial biopsies. Discuss with your doctor about when to start and how frequently these tests should occur. A hysterectomy is recommended for those with Lynch syndrome, and the timing of this surgery is a decision you make with your doctor based on national recommendations. If you have children, they should be tested for lynch syndrome. 


Make sure to check out our other article on Lynch Syndrome!

Ask your doctor if you should have genetic testing by blood or saliva to determine if your cancer is from an inherited condition.

Make sure to bring up any family history of cancer. 

Why genetic testing matters 

In summary, genetic testing is important for two main reasons. First, molecular sequencing of the tumor itself can help determine if you are eligible for specific targeted treatments like immunotherapies or some clinical trials. Second, germline testing for inherited conditions like Lynch syndrome can help to determine if you or your family members are at risk of developing other cancers (like colon or ovary). With this diagnosis, you and your family members can take steps to screen for cancer more closely, and reduce the risk of developing cancers with preventative surgeries. 

We are at a special time in cancer treatment as the research into targeted cancer drugs becomes more exciting. Remember to discuss with your doctor what genetic testing and molecular sequencing can mean for you and your family. 

For more information check out this 7 minute video