- Design
- Retrospective single-centre molecular cohort
- Population
- 33 TP53-mutated multiple-classifier endometrial carcinomas
- Primary outcome
- Copy-number status and recurrence
- Effect
- CNA-high 12/33 (36%); 6 recurrences and 3 deaths, all in CNA-high group
A French centre applied shallow whole-genome sequencing to 33 endometrial carcinomas that were both TP53-mutated and POLE-mutated or mismatch repair-deficient. Current algorithms assign these 'multiple classifiers' to the POLE or MMRd group.
Twelve (36%) were copy-number-high. These were more often non-endometrioid, high-grade and advanced stage, and had higher TP53 variant allele fractions. Over a median 12.8 months, all six recurrences and three disease-related deaths occurred in the copy-number-high group; none in the copy-number-low group.
This suggests that some multiple-classifier tumours behave like p53-abnormal cancers despite their assigned class. It is hypothesis-generating: 33 cases, short follow-up and no multivariable analysis.
- Continue to classify multiple-classifier tumours by the current ESGO/FIGO algorithm.
- Report the TP53 variant allele fraction relative to tumour cellularity where available.
- Flag high-grade, non-endometrioid morphology in multiple-classifier tumours to the tumour board.
- Do not order sWGS for routine reporting on the basis of this study.
Why it matters
It questions whether the current rule for multiple-classifier tumours places all of them correctly.
Don't overread it
A small single-centre cohort with a year's follow-up; it does not justify changing classification.
The statistics, in plain English
Six events in 33 patients cannot support a hazard estimate. The clean separation — all events in one group — is striking but fragile at this size.
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