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What Is Endometrial Cancer?
Endometrial cancer is a type of uterine cancer. It starts in the inner lining of the uterus, known as the endometrium. Uterine cancer and endometrial cancer are often used interchangeably, since endometrial cancer makes up the majority–about 90%–of cancers in the body, or corpus, of the uterus. Endometrial cancer is the most commonly diagnosed type of cancer that affects the gynecologic organs in the United States.
What Does the Endometrium Do?
The endometrium is the lining of the uterus. Throughout each menstrual cycle, the endometrium changes. Typically, once a month, it thickens to prepare for a possible pregnancy. If there is no pregnancy, the lining thins and sheds as a menstrual period. If there is a pregnancy, the lining stays to support it.
What Are the Signs and Symptoms of Endometrial Cancer?
There are a few signs and symptoms that can point to endometrial cancer. As the cancer develops and spreads, these symptoms may become more noticeable. Recognizing the potential signs and symptoms of endometrial cancer may lead to an earlier diagnosis, when it may be more easily treated. This can sometimes be difficult because some of these symptoms are similar to other more common health conditions. Therefore, it is very important to listen to your body and share anything unusual with your healthcare team.
Being persistent and proactive in communicating your signs and symptoms to your healthcare team may help lead to an earlier diagnosis.
What are the most common signs of endometrial cancer?
- Abnormal bleeding or spotting from the vagina (bleeding between periods, bleeding after menopause, or abnormal vaginal discharge)
Are there other signs and symptoms of endometrial cancer I should know about?
- Non-bloody vaginal discharge
- Pain in the pelvis
- Feeling a mass (tumor) in the pelvic area
- Sudden weight loss
These are not all of the possible signs and symptoms of endometrial cancer, so it is important to talk to your healthcare team if you notice anything unusual.
Hear From Real Endometrial Cancer Patients
"I was noticing an increase in lack of bladder control to the point of needing to have a restroom nearby. A few months later, I would also notice a small amount of vaginal discharge. As a post-menopausal woman, I thought this was strange, but it didn’t worry me. When the discharge changed color and increased in volume, I called my primary care doctor to schedule an appointment the next day. " – Cheryl, endometrial cancer survivor, 70 years old
"I started to notice my hair was falling out. Things took a turn a few months later when I started to use the restroom a lot and had really bad acid reflux. The fatigue worsened, and I started to feel abdominal fullness and pain. When I finally went back to the doctor, she told me to go to the ER. That's when they discovered I had watermelon sized tumor pressing on my kidney and causing a lot of my symptoms." – Casey, endometrial cancer survivor, 30 years old
Cheryl and Casey are paid spokespeople for GSK’s Our Way Forward. These are their personal patient experiences, and yours may be different.
What Are the Risk Factors for Endometrial Cancer?
Several factors may increase or decrease the chances of developing endometrial cancer.
How Do Family History and Biomarkers Play a Role in Endometrial Cancer?
Is Endometrial Cancer a Genetic Disease?
Endometrial cancer can have a genetic component. A family history of endometrial cancer may be associated with an increased risk of developing the disease. Read on to learn how your family history plays a role, what to ask your healthcare team about, and how to get tested.
Family History
Your genes can determine many characteristics about you, such as the color of your hair, how tall you are, and whether you may be at increased risk of developing certain diseases, such as endometrial cancer. Families with a history of Lynch syndrome, a genetic condition inherited from a parent, have a higher risk of developing endometrial cancer.
How do I learn more about my family history?
To understand your own health risks, it’s helpful to talk to your family members. Here are some key pieces of information to gather:
- Their sex, date of birth, and ethnicity
- Any medical conditions they know of, and the age they were diagnosed
- Any complications they had during pregnancy or other reproductive issues
- Their lifestyle habits, such as diet, exercise, and tobacco use
It’s also important to understand the health history of any immediate relatives who have passed away.
Other places you can look for information are:
- Public records (birth certificates, death certificates)
- Obituaries
- Baby books
Having these conversations can be challenging. If you’re unsure about discussing health history with your family, consider these tips:
- Don’t go at this alone – ask a sibling or close family member to join you
- Explain why you want to gather this information
- Respect your relatives’ privacy
- Listen without judgment
In addition to talking with family, healthcare professionals can perform molecular testing and look for biomarkers that can help determine cancer risk, prognosis, and potential treatment options.
Endometrial Cancer Biomarkers
What is a biomarker?
Biomarkers are specific characteristics found in cells, such as proteins or DNA, which can help assess your cancer risks (both of developing or disease prognosis) and treatment options. Like many other cancers, endometrial cancer has biomarkers that can be identified through testing. Key endometrial cancer biomarkers include Mismatch Repair (MMR) and Microsatellite Instability (MSI).
MMR and MSI in Endometrial Cancer
- In normal cells, mismatch repair (MMR) is a process that fixes errors in the short, repeating pieces of DNA, called microsatellites, when DNA is copied in a cell. This process helps keeps the genes in a cell stable.
- When this process is working correctly, it is referred to as proficient mismatch repair (pMMR). Approximately (or about) 70% of endometrial cancer tumors are pMMR or microsatellite stable (MSS).
- When this repair system does not work correctly, the tumor has deficient mismatch repair (dMMR).
- Eventually, the errors left behind do not get fixed and cause more errors within the microsatellites. This is known as microsatellite instability (MSI), which is common in cancer cells.
- Tumors that are dMMR or MSI-H are more common in endometrial cancer than other cancer types and are found in about 30% of patients with endometrial cancer.
- Understanding the MMR or MSI status of your tumor may help your healthcare team learn more about the cancer and determine appropriate treatment options. Tumors with dMMR/MSI-H biomarkers are more likely to respond to immunotherapy.
Determining MMR/MSI Status Through Testing
Immunohistochemistry (IHC)
- IHC is a testing method to determine MMR status. A piece, or sample, of the cancer tissue is taken out during a biopsy or surgery.
- IHC is completed in a lab that tests by adding a dye to the tissue sample.
- Once the dye is added to the sample, the lab technician takes a closer look through a microscope to determine biomarker status.
Polymerase Chain Reaction (PCR)
- Like IHC, PCR is completed in a lab to measure MSI by quickly making millions to billions of copies of a piece of DNA, so that it can be studied more closely.
Next-Generation Sequencing (NGS)
- NGS testing is also done in a lab, looking at DNA and RNA fragments like they are building blocks. This kind of test puts together the fragments to identify any changes in certain areas as they are placed together.
- Healthcare professionals can then choose medications that target these genetic changes in the tumor.
MMR and MSI are important endometrial cancer biomarkers, but there are other ones you may have. Below are other biomarkers associated with endometrial cancer:
- Estrogen and progesterone receptors (ER/PR)
ER/PR are hormone receptors found in about 57% of endometrial tumors. They may help predict how well a patient might respond to hormone therapy.
- Tumor mutational burden (TMB)
TMB measures the number of mutations within a tumor. About 15% of endometrial cancers have high TMB, which may be associated with both a better prognosis and better responses to immunotherapy.
- Polymerase epsilon (POLE) mutations
POLE mutations occur in about 10% of all endometrial cancers. These patients may be less likely to experience the cancer returning, tend to survive longer and appear to benefit less from chemotherapy and radiation.
- Human epidermal growth factor receptor 2 (HER2) proteins
Certain types of endometrial cancer have high levels of HER2 and are more likely to respond to therapies that target this biomarker. Lower HER2 levels have been associated with better survival rates.
- Phosphatase and tensin homolog (PTEN) gene mutations
PTEN mutations occur in about 45% of endometrial cancers. PTEN loss can serve as a warning sign that precancerous tissue is at higher risk of developing into endometrial cancer.
- Neurotrophic tyrosine receptor kinase (NTRK)
NTRK is a less common biomarker in endometrial tumors, but it can be useful for making treatment decisions. For patients who test positive for NTRK gene fusion, tyrosine kinase inhibitors (TKI) can be used to target cancer cells.
- P53 gene mutations
P53 mutations occur in about 15-25% of all patients with endometrial cancer but are responsible for 50-70% of endometrial cancer deaths. While these patients tend to have poor prognosis, they are also more likely to benefit from combined chemotherapy and radiation.
Knowing your biomarker status can help you and your healthcare team learn about your prognosis and help you find the treatment option that may be right for you.
How Is Endometrial Cancer Diagnosed?
Endometrial cancer is most often diagnosed after a person visits their doctor because they are experiencing symptoms.
There is currently no standard or routine screening test for endometrial cancer for early diagnosis in patients who are at average risk and have no symptoms. Because of this, it’s important to pay attention to any changes in your body that do not feel normal and talk to your doctor if you notice anything unusual. You should also talk to your doctor about when to get pelvic exams and pap smears. These tests are not specifically used to screen for endometrial cancer, but may be helpful in discovering some cases of endometrial cancer.
Examples of Endometrial Cancer Tests:
- Pelvic ultrasound
- Transvaginal ultrasound (TVUS)
- Endometrial biopsy and tissue sampling
- Dilation and Curettage (D&C)
- Hysteroscopy
- Molecular profile tests (i.e., biomarker tests)
- Additional scans or blood tests as recommended by your healthcare professional
Endometrial Cancer Grading
Following a biopsy, if cancer cells are identified, they will be graded. Grading helps doctors understand how fast the cancer may grow and spread. The grading scale looks at the cancer cells to see how much they look like normal cells, on a scale from 1 to 3. Grading helps doctors determine the best treatment approach for you.
Grade I (1) and Grade II (2)
| Likely referred to as “lower grade” |
| Cancer cells look more like normal cells |
| Cells grow and spread to other parts of the body more slowly (less aggressive) |
| Less likely to return (recur) |
Grade III (3)
| Likely referred to as “high grade” |
| Cells look very abnormal |
| Cells grow and spread to other parts of the body more quickly (more aggressive) |
| Cells look very abnormal and grow more quickly |
Endometrial Cancer Stages
After receiving a diagnosis of endometrial cancer, your healthcare professional will assign a stage to your cancer. The stage describes the amount of cancer in the body, how far it has spread, and how best to treat it. Staging is typically determined by imaging tests and blood tests. Lower numbers mean the cancer has spread less and higher numbers mean the cancer has spread more.
FIGO Staging
The following staging is called the FIGO system since it was developed by the International Federation of Gynecology and Obstetrics. Refer to the diagrams on this page to identify the locations of the body impacted by the staging.
Stage I
Cancer is found in the body (also called the corpus) of the uterus only
- Stage IA – cancer is in the endometrium (inner lining of the uterus), either less than or up to halfway through the muscle layer of the uterus (called the myometrium)
- Stage IB – cancer has spread more than halfway through the myometrium
Stage II
Cancer has spread into the connective tissues of the cervix but not outside the uterus
Stage III
Cancer has spread beyond the uterus body and cervix but not beyond the pelvis
- Stage IIIA – cancer has spread to the outer layer of the uterus and/or to the fallopian tubes and ovaries
- Stage IIIB – cancer has spread to the vagina and/or the tissues around the uterus (called the parametrium)
- Stage IIIC1 – cancer has spread to lymph nodes in the pelvis but not the bladder or rectum
- Stage IIIC2 – cancer has spread to the lymph nodes around the aorta (the largest artery of the body, which carries blood away from the heart) but not to distant sites
Stage IV
Cancer has spread beyond the pelvis
- Stage IVA – cancer has spread to the bladder and/or inner lining of the rectum
- Stage IVB – cancer has spread to other parts of the body beyond the pelvis, including the upper abdomen (belly), lymph nodes in the groin, or to more distant areas, such as the lungs, liver or bones
Types of Endometrial Cancer
Endometrial cancers are usually classified by how they look under a microscope, which offers clues about how the cancer might behave in the body. There are four main types of endometrial cancer.
Endometrioid Carcinoma
- Is the most common type of endometrial cancer, accounting for about 75% of cases
- Usually diagnosed at an earlier stage and has a high survival rate
- Depends on estrogen for growth
Serous Carcinoma
- Accounts for about 10% of endometrial cancer cases
- Tends to be more aggressive
- Usually diagnosed in later stages
- Does not depend on estrogen
Clear Cell Carcinoma
- Accounts for about 4% of endometrial cancer cases
- Tends to be more aggressive
- Usually diagnosed in later stages
- Does not depend on estrogen
Carcinosarcoma
- Also known as malignant mixed Müllerian tumors
- Accounts for 3% of endometrial cancer cases
- Most aggressive type
- Usually diagnosed in later stages
- Does not depend on estrogen
Learn Common Gynecologic Terms
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