- Design
- Retrospective single-institution molecular study
- Population
- 33 TP53-mutated multiple-classifier endometrial carcinomas
- Primary outcome
- Copy-number status and clinical events
- Effect
- CNA-high 36.4%; recurrences 6/12 CNA-high vs 0/21 CNA-low at median 12.8 months
A single-institution study in Modern Pathology (published 17 September) examined 33 endometrial carcinomas with a TP53 mutation alongside a POLE mutation or mismatch repair deficiency, the so-called multiple classifiers, using shallow whole-genome sequencing.
Twelve (36%) had high copy-number alteration and 21 low. Copy-number-high tumours were more often non-endometrioid, high grade and advanced stage, and had higher TP53 variant allele fractions. Over a median follow-up of only 12.8 months, all six recurrences and three disease-related deaths occurred in the copy-number-high group.
Current ESGO and FIGO algorithms assign these tumours to their POLE or mismatch repair category, treating the TP53 mutation as secondary. This study suggests a subset behaves more like p53-abnormal disease. It is hypothesis-generating, with small numbers and very short follow-up, and does not justify departing from the current classification.
- Continue to classify multiple-classifier endometrial carcinomas by the current algorithm, with POLE or mismatch repair status taking precedence.
- Report the TP53 status and its variant allele fraction in multiple-classifier cases.
- Flag high-grade, non-endometrioid morphology in a multiple-classifier tumour for multidisciplinary discussion.
- Consider these cases for research cohorts where copy-number profiling is available.
Why it matters
It raises the question of whether a POLE or mismatch repair label is always reassuring when TP53 is also mutated.
Don't overread it
Thirty-three patients and about a year of follow-up cannot establish prognosis; current guidelines are unchanged.
The statistics, in plain English
With six recurrences in total, the observation that all fell in one group is striking but could partly reflect chance and the higher stage in that group.
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