Cancer Dictionary · Gynaecological

Endometrial Cancer

Endometrial cancer is one of the clearest examples of a disease reorganised by molecular classification. Four groups defined by POLE status, mismatch repair status, TP53 status and the absence of these features carry distinct outlooks and different management discussions. Lynch syndrome screening is a routine part of the pathway.

Also called Uterine cancer, Cancer of the womb lining.

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The governing idea

Endometrial cancer has been reclassified around four molecular groups, and that classification now carries more prognostic weight than histology alone, which makes molecular testing part of the diagnosis rather than an addition to it.

01Before any molecular question

How it usually presents

Usually established first: histological type and grade, stage, and depth of myometrial invasion. Increasingly, molecular classification is performed alongside this rather than after it.

Usually already established

Histological type and grade
Stage and depth of invasion
Mismatch repair status by immunohistochemistry, which is often done reflexively
Whether molecular classification has been performed

Major disease categories

The divisions below are not labels. Each one changes what the treatment discussion is actually about.

POLE ultramutated

Defined by a specific type of POLE alteration. Associated with a notably favourable outlook despite features that would otherwise look concerning.

Mismatch repair deficient

Also described as MSI-high. Relevant to immunotherapy discussions and to Lynch syndrome screening.

p53 abnormal

Associated with a less favourable outlook and often managed more intensively.

No specific molecular profile

The group defined by the absence of the other three features. Managed largely on conventional features.

03What is discussed

Molecular considerations

The four-group classification uses POLE exonuclease domain mutations, mismatch repair protein loss or microsatellite instability, and TP53 abnormality. Beyond classification, PIK3CA, PTEN, ARID1A, CTNNB1 and ERBB2 are commonly altered. ERBB2 amplification is particularly relevant in serous histology. Mismatch repair deficiency here is both a treatment-relevant finding and a trigger for considering Lynch syndrome.

Biomarkers commonly discussed

POLE

Specific exonuclease domain mutations define a favourable group. Not every POLE variant counts.

MMR / MSI

Both a treatment-relevant marker and a Lynch syndrome screening trigger.

TP53

Abnormality defines the less favourable molecular group.

ERBB2 (HER2)

Amplification is particularly relevant in serous histology.

PTEN, PIK3CA, ARID1A

Commonly altered. Part of the broader molecular picture.

Oestrogen receptor

Relevant to hormonal approaches in some settings.

This is not an exhaustive list, and which markers are relevant depends on the individual case. Not every marker listed is assessed in every patient.

04What is tested, and from what

Testing, inherited risk and blood-based monitoring

Genomic testing considerations

Molecular classification is now part of how the disease is characterised, and in many pathways mismatch repair immunohistochemistry is performed reflexively on the surgical specimen. Comprehensive profiling is more often discussed in advanced or recurrent disease. Because classification affects decisions made shortly after surgery, timing is part of the discussion.

Germline considerations

Endometrial cancer is frequently the first cancer to appear in a family with Lynch syndrome, which makes it a sentinel diagnosis. Mismatch repair deficiency on the tumour prompts further evaluation to distinguish an inherited cause from a much more common non-inherited one. Where Lynch syndrome is confirmed, it changes surveillance for the patient and opens a cascade pathway for relatives, with implications for colorectal and other cancers.

Cancer genetics and hereditary risk

ctDNA and liquid biopsy considerations

ctDNA is under study in endometrial cancer rather than being established practice, with interest in residual disease detection after surgery in higher-risk molecular groups.

When molecular information matters

Testing that arrives after the decision it was meant to inform has already been made is a common and avoidable problem. This is the sequence in which molecular information tends to become relevant.

At diagnosis and surgeryMolecular classification is increasingly performed on the surgical specimen, because it informs what follows.
When mismatch repair deficiency is foundThe Lynch syndrome question follows, with implications well beyond this cancer.
Before adjuvant treatment decisionsMolecular group carries weight here, so the result needs to arrive before that discussion.
In advanced or recurrent diseaseComprehensive profiling and immune markers become more prominent.

06Take these to your team

Questions worth raising

When a decision is being made

Questions worth raising with a treating team.

Has molecular classification been performed, and which of the four groups does this cancer fall into?
If a POLE mutation is reported, is it specifically an exonuclease domain mutation of the type that defines the favourable group?
If mismatch repair deficiency is found, has the Lynch syndrome question been formally addressed rather than assumed?
In serous histology, has HER2 status been assessed?

At progression, recurrence or resistance

The molecular picture at diagnosis is not always the molecular picture later.

Has the molecular profile been reviewed at recurrence, particularly where the original assessment predated routine classification?

07What shapes eligibility

Clinical trial considerations

Molecular group and mismatch repair status are frequently written into eligibility criteria. Serous histology with HER2 amplification has its own distinct trial landscape.

Ask about trial matching

Plain-language glossary for this entry (5 terms)

Term	What it means
Molecular classification	Sorting a cancer into groups by its molecular features rather than by appearance alone.
POLE	A gene involved in copying DNA accurately. Certain mutations in it produce an enormous number of mutations and, unexpectedly, a favourable outlook.
Mismatch repair	A DNA proofreading system. When it fails, characteristic errors accumulate in repetitive stretches of DNA.
Lynch syndrome	An inherited condition affecting mismatch repair, raising the risk of several cancers.
Sentinel diagnosis	A cancer that, by appearing first, reveals an inherited condition affecting the whole family.

Where OnKommon fits

These are the services most often relevant to this cancer. Which of them applies is a clinical question, not an automatic one.

Signature STt OProfiling from an existing FFPE tissue block.See how it works HeritageInherited-risk testing, and a tested pathway for relatives.See how it works Signature STb O+The 523-gene comprehensive panel, with TMB and MSI.See how it works ClearMolecular residual disease surveillance after curative-intent treatment.See how it works

This entry is educational. It describes what is commonly discussed in this cancer, not what should happen for any individual. Which of it applies depends on the specific diagnosis, stage, prior treatment and the person themselves. Nothing here is a recommendation, and no list of biomarkers here is exhaustive. Decisions belong with a treating team who know the whole case.

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