Endometrial carcinoma: types and molecular groups
- Topic
Endometrial cancer is two diseases under the microscope and four in the genes. Knowing which one a patient has decides how aggressive it will be.
What it is
Endometrial carcinoma is the most common invasive gynecologic cancer in high-income countries and usually presents with postmenopausal bleeding. Classically it is split into endometrioid carcinoma, estrogen-related, arising from atypical hyperplasia and mostly low grade, and serous carcinoma, arising in atrophic endometrium of older women with TP53 mutation and an aggressive course. Genomic studies refined this into four molecular groups, which are now identified in practice with sequencing of POLE and immunostains for mismatch repair proteins and p53.
Key facts
- The four molecular groups are found with three tests: POLE sequencing, immunostains for MLH1, PMS2, MSH2 and MSH6, and p53 immunostaining.
- Many centres test every endometrial carcinoma for mismatch-repair loss, to find Lynch syndrome and to guide immunotherapy.
- Risk factors: obesity, diabetes, hypertension, nulliparity, early menarche and late menopause, unopposed estrogen, tamoxifen, polycystic ovary syndrome, Lynch syndrome.
- Protective: combined oral contraceptives and pregnancy.
The two classic types of endometrial carcinoma
| Feature | Endometrioid carcinoma | Serous carcinoma |
|---|---|---|
| Age | Peri- and early postmenopausal | Older postmenopausal |
| Background | Unopposed estrogen, atypical hyperplasia | Atrophic endometrium, often a polyp |
| Precursor | Atypical hyperplasia (EIN) | Serous endometrial intraepithelial carcinoma |
| Key mutations | PTEN, PIK3CA, ARID1A, KRAS, CTNNB1, mismatch repair | TP53, often with copy-number changes |
| Microscopy | Glands resembling endometrium, squamous areas | Papillae and slit-like spaces, high-grade nuclei, psammoma bodies |
| Behaviour | Usually confined to the uterus at diagnosis | Spreads to the peritoneum early, even when minimal in the uterus |
Clinical notes
- Postmenopausal bleeding brings most patients early, which is why overall survival is good for endometrioid tumours.
- Surgical stage, histologic type and molecular group together decide adjuvant treatment.
Test yourself
Think of the answer, then tap the question to see it.
Which molecular group of endometrial carcinoma has the best prognosis?
The POLE-ultramutated group, despite often looking high grade.
Why test endometrial carcinomas for mismatch repair proteins?
Loss can reveal Lynch syndrome, for which endometrial cancer is often the first tumour, and it predicts response to immunotherapy.
In what background does serous endometrial carcinoma arise?
In atrophic endometrium of older women, from serous endometrial intraepithelial carcinoma, driven by TP53 mutation.
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Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Endometrial Cancer (StatPearls (NCBI Bookshelf), 2026); Endometrial Cancer Treatment (PDQ®)–Health Professional Version (National Cancer Institute, 2026); Lynch syndrome: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026).
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Representative model, for educational purposes only.