Endometrial / Uterine Cancer
Endometrial cancer has been substantially reorganised by molecular classification, which separates it into groups whose prognosis and management discussions differ from what histology alone would suggest.
Disease categories
Major disease categories
- Endometrioid carcinoma
- Serous carcinoma
- Clear cell carcinoma
- Carcinosarcoma
- Uterine sarcoma
Molecular
Molecular considerations
Molecular classification distinguishes POLE-ultramutated, mismatch repair deficient, p53-abnormal and no-specific-molecular-profile groups. This classification is now central to how the disease is discussed.
Markers commonly discussed in endometrial / uterine cancer
- POLE
- MMR / MSI
- TP53 / p53 IHC
- HER2 (serous)
- PD-L1
- ER / PR
Not exhaustive, and not every marker is assessed in every patient. Which of these is relevant depends on the individual case and should be discussed with the treating team.
Testing
Genomic testing considerations
Molecular classification is widely discussed at diagnosis; broader profiling is used in advanced disease.
Germline
Germline considerations
Mismatch repair deficiency raises the question of Lynch syndrome, with implications for relatives.
Molecular monitoring
ctDNA and liquid biopsy considerations
Investigational in this disease.
Single-cell & computation
Single-cell and algorithmic approaches
Single-cell analysis in gynaecological cancer is applied to clonal structure at relapse, where the question is whether resistant disease was present from the outset or emerged under treatment. Single-cell DNA sequencing can identify reversion events in a subpopulation before they are detectable in bulk. Algorithmic work includes homologous recombination deficiency scoring from sequencing data, mutational signature analysis, and molecular classification pipelines.
Decisions
Treatment decision questions
Questions worth raising with a treating team when a decision is being made:
- Has molecular classification been performed?
- Has mismatch repair status been established?
- For serous disease, has HER2 been assessed?
Resistance
Resistance and recurrence questions
- Has the molecular profile been reassessed at recurrence?
Trials
Clinical trial considerations
Molecular class frequently determines the relevant trial set.
When a precision oncology review may help
A review is most useful where the standard pathway has been exhausted or where the picture is more complicated than a protocol accounts for — rare presentations, treatment resistance, complex or apparently contradictory molecular findings, or a decision between several defensible options.
The output is a structured analysis and a set of questions for the treating team. It is not treatment, and it does not replace the treating oncologist.