Endometrial cancer is the most common cancer of the uterus, making up about 95% of all cases.

It begins in the inner lining of the uterus, called the endometrium. It is the most common gynecological cancer in Canada, with approximately 8,800 Canadians diagnosed each year.

What are the types of endometrial cancer?

There are several different types of endometrial cancers, and they are grouped based on stage, grade, histotype (the type of cells the cancer is made of), and by molecular subtype (specific genetic changes in the cancer).

Does endometrial cancer spread?

Endometrial cancer might spread. Traditional surgical staging is a procedure doctors use to find out how far endometrial cancer has spread.

Staging

Surgical staging usually includes removing the uterus, fallopian tubes, and ovaries, checking nearby lymph nodes, and taking small tissue samples (biopsies). After surgery, a pathologist examines the tissue to determine the stage of the cancer, which ranges from stage I (cancer is only in the uterus) to stage IV (cancer has spread to other parts of the body). Sub-stages give more detail about how far the cancer has spread.

• Stage 1: Cancer is only found in the uterus. Sub-stages (IA, IB) describe how deeply it has grown into the wall of the uterus.
• Stage 2: Cancer is still in the uterus but has also spread to the cervix (the lower part of the uterus).
• Stage 3: The cancer has grown beyond the inside of the uterus and cervix but is still within the pelvic area or in lymph nodes in the pelvis or abdominal area. It may have reached the outer surface of the uterus, the ovaries, fallopian tubes, vagina, or nearby lymph nodes.
• Stage 4: The cancer has moved into nearby organs like the bladder or bowel, or to distant organs such as the lungs or liver.

Grading

Grading describes how different the cancer looks from normal tissue and how likely it is to grow or spread. The more the cancer cells look like normal cells, the more likely they are to behave like normal cells and grow more slowly. Grading also describes how crowded the endometrial glands are. The lining of the uterus is made up of tiny gland-like structures. In healthy tissue, these glands are spaced out. In cancer, they can become packed tightly together, appearing more crowded.

• Grade 1 (low grade): Cells look fairly normal and are only slightly crowded. These cancers usually grow slowly and have a lower risk of spreading.
• Grade 2 (intermediate grade): Cells are more crowded and look a bit more abnormal, but often still behave like low-grade tumors.
• Grade 3 (high grade): Cells look very abnormal and look more like solid layers of tumour cells rather than forming normal gland structures. These cancers are more likely to spread or come back after treatment.

Histotype

Histotype describes the type of endometrial cancer based on how the tumor looks under a microscope.

• Endometrioid: This is the most common type of endometrial cancer (over 70% of cases) and can be grade 1, 2 or 3.
• Other types: Serous, clear cell, carcinosarcoma, dedifferentiated/undifferentiated, mesonephric-like, and gastric-type cancers. These are all less common and are usually high grade (grade 3).

Molecular Classification

Knowing the molecular subtype helps doctors predict how likely the cancer is to come back (recur) and choose the most effective treatment. The four molecular subtypes of endometrial cancer are:

1. POLE mutated: These cancers have specific mutations in a gene called POLE. They often look aggressive under the microscope but have an excellent prognosis and can often be treated with surgery alone, without the need for chemotherapy or radiation.
2. Mismatch Repair Deficient (MMR Deficient, or MMRd): In these cancers, the body’s “DNA repair system” does not work properly. As a result, mistakes in the DNA build up over time, allowing the cancer to grow. MMRd cancers may be linked to an inherited condition called Lynch Syndrome. These cancers have a moderate chance of recurring (they are more likely to come back than POLE cancers, but less likely to come back than p53-abnormal cancers, which are described below). Many patients with MMRd endometrial cancers respond well to immunotherapy, a treatment that helps the immune system recognize and attack cancer cells.
3. p53 Abnormal: These cancers have a change in p53 protein expression or have changes in a gene called TP53, which normally helps control how cells grow and divide. When this gene isn’t working properly, the cancer can grow and spread more quickly. Because of this, p53-abnormal cancers are usually more aggressive and may require more extensive surgery and treatment.
4. No Specific Molecular Profile (NSMP): These cancers don’t have any of the changes seen in the other groups — no POLEmutation, MMR deficiency, or p53 abnormality. They are considered to have a moderate risk of coming back, similar to MMR-deficient cancers. Doctors may also look at estrogen receptor (ER) levels. ER-positive (ER+) means the cancer cells have receptors that respond to estrogen, while ER-negative (ER–) means they do not. This information can help guide treatment decisions. For example, ER-positive cancers may respond to hormone therapy, while ER-negative cancers are often more aggressive and may require additional treatments like chemotherapy or radiation.