Endometrial carcinoma

Last medical review:

Endometrial carcinoma (also called endometrial cancer) begins in the lining of the uterus (endometrium). More than 95% of all uterine cancers are endometrial carcinomas.

Research has shown that classifying endometrial carcinoma into different molecular subtypes and into a cellular substype is the best way to help decide what treatments are used and determine prognosis.

Molecular subtypes

Endometrial carcinoma is classified based on the changes (mutations) that have happened to the genes inside the cancer cells. Doctors use a combination of pathology tests and DNA genetic sequencing to divide endometrial carcinomas into 1 of 4 main molecular subtypes:

POLEmut endometrial carcinoma has the most mutations in the cancer cells of the four molecular subtypes. It often looks very high grade when looked at through a microscope, but usually has an excellent outcome. POLEmut stands for DNA polymerase epsilon mutated.

MMRd endometrial carcinoma is when one of the MMR proteins is missing so the MMR gene is no longer working properly, and genes aren’t repaired as they should be. MMRd endometrial cancer is linked to Lynch syndrome. MMRd stands for mismatch repair deficient. It may be called microsatellite instability (MSI).

p53abn endometrial carcinoma is the most aggressive subtype, which means it can grow fast, is likely to spread, and is at increased risk of coming back (recurring). It happens when the TP53 gene is mutated and causes cells with damaged DNA to grow and divide out of control. p53abn stands for abnormal tumour protein 53.

NSMP endometrial carcinoma makes up about 50% of all endometrial cancers. It includes cancers that have genetic changes that are not POLEmut, MMRd or p53abn. NSMP stands for non-specific molecular profile.

Cellular subtypes

Doctors also look at an endometrial carcinoma through a microscope to find out more about the cancer, including the type of cell and grade. This information can help plan treatment, especially for NSMP endometrial carcinoma.

Endometrioid adenocarcinoma is the most common subtype and makes up about 80% of all endometrial carcinomas. It forms from the glands of the endometrium. Sometimes endometrioid adenocarcinomas can have squamous cells, which look like skin cells (called squamous cell differentiation). When the cancer is made up of both gland cells and squamous cells, it's called adenosquamous carcinoma (or mixed cell carcinoma).

Serous carcinoma looks more like high-grade serous ovarian cancer. It tends to come back (recur). Most serous cancers are p53abn molecular subtype.

Carcinosarcoma has features of both carcinomas and sarcomas and is poorly differentiated. It's also called malignant mixed mesodermal tumour or malignant mixed mullerian tumour (MMMT).

Other rare cellular subtypes of endometrial carcinoma include:

  • clear cell carcinoma
  • mesonephric-like adenocarcinoma
  • gastric-type carcinoma
  • squamous cell carcinoma
  • transitional cell carcinoma
  • small cell carcinoma
  • undifferentiated carcinoma
  • dedifferentiated carcinoma

Expert review and references

  • Tien Le, MD, FRCSC, DABOG
  • Alektiar KM, Abu-Rustum NR, Makker V, et al. Cancer of the uterine body. Devita VT, Lawrence TS, Rosenberg SA, eds. DeVita Hellman and Rosenberg's Cancer: Principles and Practice of Oncology. 12th ed. Philadelphia, PA: Wolters Kluwer; 2023: Kindle version, chapter 50, https://read.amazon.ca/?asin=B0BG3DPT4Q&language=en-CA.
  • Berek JS, Matias-Guiu X, Creutzberg C, et al. FIGO staging of endometrial cancer: 2023. International Journal of Gynecology and Obstetrics. 2023: 162:383–394.
  • Gockley A. Endometrial cancer: special conditions. Chi D, Berchuck A, Dizon DS, Yashar CM. Principles and Practice of Gynecologic Oncology. 8th ed. Philadelphia, PA: Wolters Kluwer Health; 2025: 5.8:181–182.
  • Hacker NF, Friedlander ML. Uterine cancer. Berek J, Hacker NF. Berek and Hacker's Gynecologic Oncology. 7th ed. Philadelphia, PA: Wolters Kluwer; 2021: 10:371–420.
  • PDQ Adult Treatment Editorial Board. Endometrial Cancer Treatment (PDQ®)–Health Professional Version. National Cancer Institute; 2024. https://www.cancer.gov/.

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