by Jason Wasserman MD PhD FRCPC
January 20, 2026
Endometrial endometrioid adenocarcinoma is a type of cancer that starts in the endometrium, the inner lining of the uterus. It is the most common type of endometrial cancer and typically affects women over the age of 50 years. Endometrial endometrioid adenocarcinoma is believed to develop from a pre-cancerous condition called atypical endometrial hyperplasia.

The most common symptoms of endometrial endometrioid adenocarcinoma include:
If you experience any of these symptoms, it’s important to consult a doctor for further evaluation.
The exact cause of endometrial endometrioid adenocarcinomais not fully understood, but several risk factors may contribute to its development, including:
A biopsy is used to diagnose endometrial endometrioid adenocarcinoma. A small tissue sample is taken from the endometrium and examined under a microscope by a pathologist. The pathologist looks for abnormal cells and their growth patterns, which helps confirm the diagnosis.
When examined under a microscope, endometrial endometrioid adenocarcinoma displays a variety of growth patterns, reflecting the abnormal way the tumour cells are organized. The tumour typically shows a combination of glandular, papillary, and solid growth:
In addition to these patterns, squamous differentiation is common in endometrial endometrioid carcinoma. This means that some areas of the tumour start to look like squamous cells, which are flat cells that typically line the surface of certain tissues, such as the skin. Squamous differentiation can give parts of the tumour a more solid appearance and is a feature frequently observed in this type of cancer.

The FIGO grade is a system pathologists use to assess how much the tumour cells in endometrial endometrioid carcinoma differ from normal endometrial cells. This assessment is done by examining the tumour under a microscope and determining the percentage of non-squamous solid growth (areas where the tumour cells form solid clusters rather than the organized glands seen in healthy tissue).
The FIGO grade is important because it helps guide treatment decisions and provides information about the tumour’s likely behaviour. Higher-grade tumours grow more quickly and have a greater chance of spreading (metastasizing), while lower-grade tumours are generally less aggressive.
The FIGO system divides tumours into two main categories:
Biomarkers are tests performed on tumour tissue to better understand how a cancer behaves and which treatments may be most effective. These tests may include immunohistochemistry (to look for specific proteins in tumour cells) and molecular testing (to look for changes in DNA). Not all biomarkers are tested in every case.
Mismatch repair proteins help normal cells fix small mistakes that occur when DNA is copied. The four most commonly tested proteins are MLH1, PMS2, MSH2, and MSH6, which work together in pairs.
Pathologists usually test MMR proteins using immunohistochemistry. Results are reported as either retained expression (normal) or loss of expression (abnormal).
Loss of one or more MMR proteins means the tumour is MMR-deficient. This is important because MMR-deficient tumours may respond well to immunotherapy. MMR testing is also used to identify patients who may have Lynch syndrome, a hereditary condition associated with an increased risk of several cancers, including endometrial cancer.
ER and PR are proteins that allow tumour cells to respond to the hormones estrogen and progesterone. These markers are tested using immunohistochemistry and are reported as positive or negative, sometimes with a percentage showing how many tumour cells express the receptor.
Endometrial endometrioid adenocarcinomas are often ER- and PR-positive, especially low-grade tumours. Tumours that express these receptors generally have a better prognosis and may respond to hormone-based therapies in certain clinical settings.
p53 is a tumour suppressor protein that helps control cell growth and repair damaged DNA. In most low-grade endometrial endometrioid adenocarcinomas, p53 shows a wild-type pattern, meaning the protein behaves normally. This is reported as p53 wild type and is associated with more typical, less aggressive tumour behaviour.
An abnormal p53 result indicates that the TP53 gene is altered. This is usually reported as aberrant, mutant-type, or abnormal p53 expression. Tumours with abnormal p53 tend to behave more aggressively and may be treated similarly to serous carcinoma, even if they appear endometrioid under the microscope.
CTNNB1 is a gene involved in cell signaling and growth. Mutations in CTNNB1 are commonly found in low-grade endometrial endometrioid adenocarcinoma.
When present, CTNNB1 mutations may be associated with a higher risk of recurrence, even in early-stage disease. Results are usually reported as mutated or wild-type (normal).
KRAS is a gene involved in pathways that regulate cell growth. Mutations in KRAS are found in a subset of endometrial endometrioid adenocarcinomas.
These mutations may be associated with more aggressive tumour behaviour and may influence how the tumour responds to certain targeted treatments.
PIK3CA plays a role in regulating cell growth and survival. Mutations in this gene are common in endometrial endometrioid adenocarcinoma.
PIK3CA mutations may influence tumour growth and, in some cases, help guide decisions about targeted therapies, particularly in advanced or recurrent disease.
POLE mutations occur in a small subset of endometrial endometrioid adenocarcinomas. These tumours typically have many DNA mutations but behave in a less aggressive way.
Tumours with POLE mutations are associated with an excellent prognosis and a very low risk of recurrence, even when other high-risk features are present.
PTEN is a tumour suppressor gene that helps regulate cell growth. Loss or mutation of PTEN is very common in endometrial endometrioid adenocarcinoma and is often an early event in tumour development.
Although PTEN mutations are frequent, they are not usually used alone to predict prognosis or guide treatment decisions.
Many endometrial cancers can be grouped into four molecular subtypes, based on large genomic studies such as those from The Cancer Genome Atlas (TCGA). The biomarkers described above help place a tumour into one of these categories, which can provide important prognostic information.
Understanding which molecular subtype a tumour belongs to helps doctors better estimate prognosis and choose the most appropriate treatment.
The myometrium is the thick muscular layer of the uterus. Myometrial invasion occurs when the cancer spreads from the inner lining of the uterus (the endometrium) into the myometrium. The depth of myometrial invasion is important because the more deeply the tumour invades, the higher the risk of spreading to other body parts.
Most pathology reports for endometrial endometrioid adenocarcinoma will describe the amount of myometrial invasion in millimetres and as a percentage of the total myometrial thickness. This information is used to stage the tumour and to plan treatment.
Cervical stromal invasion means that the cancer has spread from the body of the uterus into the cervix, which is the lower part of the uterus that connects to the vagina. This type of invasion indicates a more advanced stage of cancer and may influence treatment decisions, such as the need for more extensive surgery or radiation therapy.
The uterus is closely connected to several other organs and tissues, such as the ovaries, fallopian tubes, vagina, bladder, and rectum. The term “adnexa” refers to the fallopian tubes, ovaries, and ligaments directly linked to the uterus. As a tumour grows, it can spread into any of these organs or tissues. In such cases, some parts of these organs or tissues may have to be removed along with the uterus. A pathologist will thoroughly examine these organs or tissues for tumour cells, and the findings will be detailed in your pathology report. The presence of tumour cells in other organs or tissues is significant, as it raises the pathologic tumour stage and is linked with a poorer prognosis.
Lymphatic invasion occurs when cancer cells enter the lymphatic system, a network of vessels that helps fight infection. Vascular invasion refers to cancer cells entering the blood vessels. Both lymphatic and vascular invasion are important because they indicate that the cancer is more likely to spread (metastasize) to other body parts, including lymph nodes and distant organs. These findings are often included in a pathology report to help guide treatment decisions.

A margin refers to the edge of the tissue removed during surgery, such as a hysterectomy. After the surgery, pathologists examine the margins of the tissue under a microscope to check for any remaining cancer cells. In the case of endometrial endometrioid carcinoma, several specific margins are carefully evaluated:
If any of these margins contain cancer cells, it is referred to as a positive margin, which may mean that some tumour cells were left behind after surgery. A negative margin means no cancer cells were found at the edges, suggesting that the tumour was completely removed. Clear margins are important for reducing the risk of the cancer returning, and positive margins may lead to recommendations for additional treatments, such as radiation therapy.
Lymph nodesLymph nodes are small, bean-shaped structures that are part of the lymphatic system, which helps fight infection and remove waste from the body. Lymph nodes contain immune cells that filter lymph fluid, which travels through lymphatic vessels, and help trap harmful substances like bacteria or cancer cells. Lymph nodes are located throughout the body, including in the pelvis and abdomen, close to the uterus.
In the context of endometrial endometrioid carcinoma, lymph nodes are examined because this type of cancer has a higher risk of spreading beyond the uterus, particularly to nearby lymph nodes. For this reason, your surgeon may remove lymph nodes from the pelvis or abdomen, which are then sent to the pathologist for examination under a microscope. This is done to check for the presence of metastatic cancer (cancer that has spread from the primary tumour to other areas of the body).
Examining lymph nodes is important for several reasons:

Pathologists use the term ‘isolated tumour cells’ to describe a group of tumour cells that measures 0.2 mm or less and is found in a lymph node. If only isolated tumour cells are found in all the lymph nodes examined, the pathologic nodal stage is pN1mi.
A ‘micrometastasis’ is a group of tumour cells measuring from 0.2 mm to 2 mm that is found in a lymph node. If only micrometastases are found in all the lymph nodes examined, the pathologic nodal stage is pN1mi.
A ‘macrometastasis’ is a group of tumour cells measuring more than 2 mm and found in a lymph node. Macrometastases are associated with a worse prognosis and may require additional treatment.
The pathologic stage for endometrial endometrioid adenocarcinoma is based on the TNM staging system, an internationally recognized system created by the American Joint Committee on Cancer. This system uses information about the primary tumour (T), lymph nodes (N), and distant metastatic disease (M) to determine the complete pathologic stage (pTNM). Your pathologist will examine the tissue submitted and give each part a number. In general, a higher number means a more advanced disease and a worse prognosis.
Endometrial endometrioid adenocarcinoma is given a tumour stage between T1 and T4 based on the depth of myometrial invasion and growth of the tumour outside of the uterus.
Based on the examination of lymph nodes from the pelvis and abdomen, endometrial endometrioid carcinoma is given a nodal stage from N0 to N2.
The FIGO staging system, developed by the International Federation of Gynecology and Obstetrics, is a standardized way of classifying endometrial cancers based on how far they have spread. This system is important because it helps doctors determine the extent of the cancer, plan appropriate treatment, and estimate the prognosis (the likely disease outcome).