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# 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.

Updated Nov 12, 2026

## Key points

- Endometrioid (the majority): perimenopausal, obesity and estrogen, atypical hyperplasia precursor, PTEN and PIK3CA, good prognosis when low grade.
- Serous: older women, atrophic endometrium, serous intraepithelial carcinoma precursor, TP53, early peritoneal spread, poor prognosis.
- POLE-ultramutated: very many mutations, often high-grade looking but excellent prognosis.
- Mismatch-repair deficient (MSI): MLH1 promoter methylation or Lynch syndrome; endometrial cancer is often the first cancer in Lynch.
- Copy-number low (no specific molecular profile): mostly low-grade endometrioid, intermediate prognosis; p53-abnormal (copy-number high): serous and some high-grade endometrioid, worst prognosis.

## 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.

## Memory aid

Endometrioid is the estrogen child that grows slowly at home; serous is the p53 runaway that leaves the uterus early.

## 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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## Elsewhere in DurgiPedia

- [Oncogenes and tumour suppressor genes](https://durgical.com/en/biochemistry/topics/oncogenes-and-tumour-suppressor-genes/)

## Connections

## Related 8

- [Endometrioid endometrial carcinoma](https://durgical.com/en/general-pathology/endometrioid-endometrial-carcinoma/)
- [High-grade endometrial cancers: serous, clear cell, carcinosarcoma](https://durgical.com/en/general-pathology/high-grade-endometrial-cancers-serous-clear-cell-carcinosarcoma/)
- [Endometrial polyps and hyperplasia](https://durgical.com/en/general-pathology/endometrial-polyps-and-hyperplasia/)
- [Genomic instability: mismatch repair, BRCA and xeroderma pigmentosum](https://durgical.com/en/general-pathology/genomic-instability-mismatch-repair-brca-and-xeroderma-pigmentosum/)
- [Hereditary cancer syndromes: the table to know](https://durgical.com/en/general-pathology/hereditary-cancer-syndromes-the-table-to-know/)
- [Molecular pathology: PCR, FISH, sequencing and liquid biopsy](https://durgical.com/en/general-pathology/molecular-pathology-pcr-fish-sequencing-and-liquid-biopsy/)
- [Immunohistochemistry: the principle and the markers to know](https://durgical.com/en/general-pathology/immunohistochemistry-the-principle-and-the-markers-to-know/)
- [Obesity: leptin, adipokines and its consequences](https://durgical.com/en/general-pathology/obesity-leptin-adipokines-and-its-consequences/)

## Related conditions 6

- [Endometrial cancer](https://durgical.com/en/conditions/endometrial-cancer/)
- [Lynch syndrome (hereditary non-polyposis colorectal cancer)](https://durgical.com/en/conditions/lynch-syndrome/)
- [Obesity](https://durgical.com/en/conditions/obesity/)
- [Endometrial hyperplasia](https://durgical.com/en/conditions/endometrial-hyperplasia/)
- [Polycystic ovary syndrome](https://durgical.com/en/conditions/polycystic-ovary-syndrome/)
- [Type 2 diabetes mellitus](https://durgical.com/en/conditions/type-2-diabetes-mellitus/)

[← All of general pathology](https://durgical.com/en/general-pathology/)

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](https://www.ncbi.nlm.nih.gov/books/NBK525981/) (StatPearls (NCBI Bookshelf), 2026); [Endometrial Cancer Treatment (PDQ®)–Health Professional Version](https://www.cancer.gov/types/uterine/hp/endometrial-treatment-pdq) (National Cancer Institute, 2026); [Lynch syndrome: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/lynch-syndrome/) (MedlinePlus, US National Library of Medicine, 2026).

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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/endometrial-carcinoma-types-and-molecular-groups/