Endometrial Cancer Facts
Endometrial Cancer Facts
Cancer begins when cells in the body start to grow out of control. Endometrial cancer starts in the cells that line the inside of the uterus, called the endometrium. The endometrium is the inner layer of the uterus and is the tissue that sheds each month during menstruation.
When you have endometrial cancer, cells in the endometrium do not follow the normal cell cycle. Healthy cells grow, copy themselves, and then die. Cancer cells change, grow faster than normal, and do not die the way they should.
THE BASICS: Endometrial cancer is the most common cancer of the female reproductive system in the United States. It begins in the lining of the uterus called the endometrium. Most endometrial cancers are adenocarcinomas which are cancers that start in gland cells. The most important risk factors are conditions that increase exposure to estrogen without adequate progesterone, including obesity, hormone therapy with estrogen alone, and certain medical conditions. When caught at an early stage, endometrial cancer is highly curable.
What is the uterus?
The uterus is a hollow, pear-shaped organ in the pelvis where a fetus develops during pregnancy. It has two main layers:
The endometrium. The inner lining of the uterus that grows and sheds each menstrual cycle.t
The myometrium. The thick outer muscular wall of the uterus.
The uterus is connected to the fallopian tubes, which carry eggs from the ovaries, and to the cervix, which connects the uterus to the vagina. Endometrial cancer begins in the endometrium and should not be confused with uterine sarcoma, a much rarer cancer that starts in the muscle layer called the myometrium.
How endometrial cancer starts
Most endometrial cancers develop when changes build up in the DNA of cells in the endometrium. These genetic changes can be driven by prolonged exposure to estrogen without enough progesterone to balance it. This hormonal imbalance causes the endometrium to grow thicker than normal, which is called endometrial hyperplasia. Over time, some of these abnormal cells can become cancerous.
Some endometrial cancers, particularly higher-grade types, are not driven by estrogen but by other genetic changes, including changes in the mismatch repair genes (which also cause Lynch syndrome) and mutations in the POLE gene.
How does endometrial cancer affect the body?
As endometrial cancer grows, it can affect many parts of the body:
How endometrial cancer affects the uterus
Endometrial cancer begins in the inner lining of the uterus and may grow into the muscular wall of the uterus. It can cause abnormal uterine bleeding, pelvic pain, and other symptoms. As it grows deeper, it may eventually spread beyond the uterus.
How endometrial cancer affects the lymph nodes
Endometrial cancer can spread to lymph nodes in the pelvis and around the aorta, the large blood vessel in the abdomen. The presence or absence of lymph node involvement is an important factor in staging and treatment planning.
How endometrial cancer affects other organs
When cancer spreads to other parts of the body, it has metastasized. Endometrial cancer most commonly spreads first to the cervix, ovaries, fallopian tubes, vagina, and pelvic lymph nodes. When it spreads further, it may travel to the lungs, liver, bones, and brain.
Types of endometrial cancer
Endometrial cancers are classified by the type of cell in which they begin and by how abnormal the cells look under a microscope:
Endometrioid adenocarcinoma. The most common type, making up about 80% of endometrial cancers. These cancers start in gland cells of the endometrium. Lower-grade endometrioid cancers tend to be associated with estrogen exposure and have a better prognosis.
Uterine serous carcinoma. A high-grade, aggressive type that accounts for about 10% of cases. Serous carcinomas behave more aggressively and are treated more intensively even when diagnosed at an early stage.
Clear cell carcinoma. Another less common, high-grade type with an aggressive behavior similar to serous carcinoma.
Carcinosarcoma (malignant mixed Müllerian tumor). A rare, very aggressive type that has features of both carcinoma and sarcoma. It is now classified and treated as a high-grade endometrial carcinoma.
Mucinous and other rare subtypes. Several other rare types make up a small fraction of endometrial cancers.
Molecular subtypes of endometrial cancer
The Cancer Genome Atlas (TCGA) identified four molecular subtypes of endometrial cancer that help predict prognosis and guide treatment decisions:
POLE ultramutated. Cancers with mutations in the POLE gene. These have a very large number of mutations but have an excellent prognosis despite often being high grade.
Mismatch repair deficient (MMRd). Cancers with defects in the mismatch repair system, which can be caused by Lynch syndrome or by a process called promoter hypermethylation. These cancers respond well to immunotherapy.
Copy number low (no specific molecular feature). Cancers that do not fall into the other categories. Outcomes are intermediate.
Copy number high/TP53 mutant. Cancers with TP53 mutations, including most serous carcinomas. These have the worst prognosis.
Related conditions
Certain conditions can be associated with a higher risk of developing endometrial cancer:
Endometrial hyperplasia. A thickening of the endometrium that can progress to cancer, particularly atypical hyperplasia.
Lynch syndrome. An inherited condition caused by mutations in mismatch repair genes that significantly increases lifetime risk of endometrial and colorectal cancers.
Polycystic ovary syndrome (PCOS). A hormonal condition associated with irregular ovulation and estrogen excess that increases endometrial cancer risk.