Endometrioid adenocarcinoma is the most common type of uterine (endometrial) cancer, accounting for about 80% of all cases. It develops from the glandular cells that line the inside of the uterus. The name describes what the cancer cells look like under a microscope: they form round or oval glands lined by column-shaped cells, resembling normal endometrial tissue. Because it tends to cause noticeable symptoms early, most cases are caught before the cancer has spread.
How It Develops
This cancer typically arises in a setting of excess estrogen that isn’t balanced by progesterone. Estrogen stimulates the uterine lining to grow. When that stimulation goes on too long without the counterbalancing effect of progesterone, the lining can develop abnormal overgrowth (called endometrial hyperplasia), which over time can progress to cancer.
Several factors create that hormonal imbalance. Obesity is one of the strongest: fat tissue produces estrogen, and the risk increases with higher BMI. Postmenopausal women who used estrogen-only hormone therapy have roughly 1.6 times the risk compared to those who didn’t, and being overweight on top of that compounds the effect. Other risk factors include early first periods, late menopause, and never having been pregnant, all of which increase lifetime estrogen exposure.
A smaller but important group of cases is linked to Lynch syndrome, an inherited condition caused by mutations in DNA repair genes (most often MLH1, MSH2, or MSH6). Women with Lynch syndrome have a significantly higher lifetime risk of endometrial cancer. If you’ve been diagnosed at a young age or have a strong family history of colon, ovarian, or uterine cancers, genetic testing may be worth discussing.
Common Symptoms
The most common early sign is abnormal vaginal bleeding. For postmenopausal women, that means any bleeding at all. For premenopausal women, it can show up as bleeding between periods or unusually heavy periods. Pelvic pain is another possible symptom, though it’s less common in early stages. Because bleeding tends to prompt a visit to the doctor relatively early, most endometrioid adenocarcinomas are diagnosed before they’ve spread beyond the uterus.
How It’s Diagnosed
Ultrasound is usually the first step when a woman reports abnormal bleeding. A transvaginal ultrasound can measure the thickness of the uterine lining and flag anything unusual. If the lining looks abnormally thick or irregular, the next step is an endometrial biopsy, a brief office procedure where a thin tube is used to collect a small sample of tissue from the uterine lining.
The biopsy is what confirms the diagnosis. A pathologist examines the tissue under a microscope, looking for those characteristic glandular structures and abnormal cells. This examination also determines the cancer’s grade and type, both of which are critical for treatment planning. If cancer is confirmed, imaging with MRI or additional ultrasound helps assess how far the tumor extends before surgery.
Grading: What the Numbers Mean
Endometrioid adenocarcinoma is graded from 1 to 3 using the FIGO system, which is based on how much of the tumor grows in disorganized, solid sheets rather than forming recognizable gland structures. The more solid growth, the more aggressive the cancer tends to be.
- Grade 1: 5% or less of the tumor is solid. These are well-differentiated, meaning the cells still look a lot like normal tissue. This is the most common and generally has the best outlook.
- Grade 2: 6% to 50% solid growth. Moderately differentiated.
- Grade 3: More than 50% solid growth. These are considered high-grade and behave more aggressively. Grade 3 tumors often develop from pre-existing endometrial hyperplasia, just like lower-grade tumors, but the cells have become significantly more abnormal.
A pathologist can also upgrade a tumor if the cells themselves look especially abnormal (marked nuclear atypia), even if the overall architecture would otherwise suggest a lower grade.
Molecular Subtypes
Beyond the microscope-based grading, researchers have identified four molecular subtypes of endometrial cancer that help predict how the disease will behave. These are increasingly used alongside traditional grading to guide treatment decisions.
Two of these subtypes are especially relevant to endometrioid adenocarcinoma. The “copy number low” subtype is the classic profile: few large-scale genetic changes, frequent mutations in genes like PTEN (lost in up to 69% of sporadic cases and 86% of Lynch syndrome cases) and KRAS, and relatively few mutations in TP53. These tumors tend to be lower grade with a favorable prognosis. The “POLE ultramutated” subtype carries an enormous number of mutations but, paradoxically, has an excellent prognosis, likely because the immune system recognizes and attacks these highly abnormal cells.
The other two subtypes, “microsatellite instability hypermutated” and “copy number high,” have intermediate and poor prognoses respectively. Some endometrioid tumors that look low-risk under the microscope turn out to have the copy-number-high profile more typical of aggressive serous cancers, which is one reason molecular testing is becoming standard practice.
Ovarian Endometrioid Adenocarcinoma
The same cell type can also give rise to cancer in the ovary. Ovarian endometrioid adenocarcinoma is less common than the uterine version but has a notable connection to endometriosis, a condition where tissue similar to the uterine lining grows outside the uterus. Endometriosis is found in 30% to 40% of ovarian endometrioid cancers, and women with endometriosis have a two- to three-fold increased risk of ovarian cancer overall. Research has identified mutations in a gene called ARID1A as a major molecular driver of both endometrioid and clear-cell ovarian cancers that arise from endometriosis.
Treatment
Surgery is the cornerstone of treatment. For early-stage disease, the standard approach is removal of the uterus along with both ovaries and fallopian tubes, typically done through a minimally invasive (laparoscopic) procedure. Most women with early-stage, low-grade endometrioid adenocarcinoma are treated with surgery alone and need no further therapy.
Whether additional treatment is recommended after surgery depends on specific findings from the pathology report. The key factors are grade, how deeply the tumor has grown into the muscular wall of the uterus, and whether cancer cells are found in lymph nodes or other tissues. For tumors that have invaded more than halfway through the uterine wall, or for grade 3 tumors with any invasion, radiation therapy is typically added. This may involve internal radiation (brachytherapy) delivered directly to the top of the vagina, external beam radiation, or both.
Chemotherapy enters the picture for higher-risk situations: grade 3 tumors, cancer that has spread to the cervix or beyond the uterus, and recurrent disease. For advanced-stage cancers, the approach is usually surgery followed by a combination of chemotherapy and radiation. Women who cannot undergo surgery for medical reasons may be treated with radiation alone, though outcomes are generally better when surgery is part of the plan.
Prognosis by Stage
The outlook for endometrioid adenocarcinoma is strongly tied to stage at diagnosis, and the news is generally encouraging because most cases are caught early. Roughly 75% of endometrial cancers are diagnosed at stage I, when the cancer is still confined to the uterus. Five-year survival for stage I disease is above 90% for grade 1 and grade 2 tumors.
Survival decreases with more advanced stages. Stage II (cancer extending into the cervix) and stage III (spread to nearby tissues or lymph nodes) carry progressively lower but still meaningful survival rates, especially with combined treatment. Stage IV disease, where cancer has spread to distant organs, has a significantly worse prognosis. Grade matters at every stage: a grade 1 tumor caught at stage III will generally do better than a grade 3 tumor at the same stage. The molecular subtype adds another layer of information, with POLE-mutated tumors doing well even at higher stages and copy-number-high tumors requiring more aggressive treatment regardless of how they look under the microscope.