# p53-abnormal endometrial cancer, including uterine serous carcinoma

Source: https://onco.cc/cancers/endometrial-p53-abnormal/  
OnCo record `endometrial-p53-abnormal` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

p53-abnormal endometrial cancer is the aggressive class, dominated by serous carcinoma, whose cells have lost the p53 guardian gene and carry scrambled chromosomes. It is the one group that clearly gains from adding chemotherapy to radiotherapy after surgery, and about a quarter of serous tumours overexpress HER2, which trastuzumab and trastuzumab deruxtecan can target.

## Summary

Abnormal p53 immunohistochemistry, either strong diffuse nuclear staining or complete absence, marks a TP53 mutation and defines the copy-number-high class of the TCGA. Uterine serous carcinoma is its archetype: a tumour of older, often thinner women that arises from atrophic endometrium through serous endometrial intraepithelial carcinoma, spreads through the peritoneum like ovarian cancer and is p53-abnormal in almost every case. Carcinosarcoma, clear cell carcinoma and a fifth of grade 3 endometrioid tumours also fall into the class. HER2 is amplified or overexpressed in about a quarter to a third of serous carcinomas, PIK3CA and PPP2R1A mutations are common, and there are no POLE or mismatch-repair defects. Even stage IA disease confined to a polyp can recur at a distance, so full staging with omental sampling is standard.

PORTEC-3 randomised women with high-risk endometrial cancer to pelvic radiotherapy alone or chemoradiation followed by four cycles of carboplatin-paclitaxel; overall survival at five years was 81.4 percent against 76.1 percent, with a hazard ratio of 0.70, and the molecular analysis showed the benefit was concentrated in p53-abnormal tumours, which had the worst outcome of the four classes and the largest absolute gain from chemotherapy. The ESGO/ESTRO/ESP guideline therefore recommends chemotherapy with or without radiotherapy for p53-abnormal disease from stage I with myometrial invasion onwards. For HER2-positive serous carcinoma a randomised phase 2 trial added trastuzumab to carboplatin-paclitaxel and improved progression-free and overall survival, which the NCCN adopted for advanced and recurrent disease. In DESTINY-PanTumor02 trastuzumab deruxtecan produced responses in 57.5 percent of HER2-expressing endometrial cancers and 84.6 percent of those with 3+ staining, earning a tumour-agnostic approval for HER2 3+ tumours in 2024.

The RAINBO p53abn-RED trial is testing adjuvant chemoradiation with or without the PARP inhibitor olaparib, on the grounds that p53-abnormal tumours share homologous recombination defects with high-grade serous ovarian cancer. DESTINY-Endometrial01 is testing trastuzumab deruxtecan with pembrolizumab or rilvegostomig in the first line for HER2-expressing disease, and WEE1 and ATR inhibitors are in earlier trials because p53-null cells depend on the remaining cell-cycle checkpoints. Checkpoint inhibitors have modest activity in the class, and these are the tumours that most need new drugs.

## Fields

- Kind: Cancer
- Last checked: 2026-09-17
- Also known as: p53abn endometrial cancer; Copy-number-high endometrial cancer; Uterine serous carcinoma; Uterine papillary serous carcinoma; Serous-like endometrial cancer
- Tags: subtype-page
- Group: gynaecologic
- Burden: About fifteen percent of endometrial cancers but more than half of the deaths; the class includes most serous carcinomas, most carcinosarcomas and a share of grade 3 endometrioid and clear cell tumours, and it recurs distantly even when caught at an early stage.
- Subtypes: Uterine serous carcinoma (p53-abnormal in nearly all cases); HER2-positive serous carcinoma (about a quarter to a third); Serous endometrial intraepithelial carcinoma (precursor); p53-abnormal grade 3 endometrioid carcinoma; p53-abnormal clear cell carcinoma; Carcinosarcoma (biphasic, usually p53-abnormal); Stage I to III p53abn (RAINBO p53abn-RED, chemoradiation with or without olaparib)
- Biomarkers: p53 immunohistochemistry (mutant-pattern staining or null); TP53 sequencing where staining is equivocal; HER2 immunohistochemistry and in situ hybridisation (serous and carcinosarcoma); Copy-number burden and homologous recombination deficiency; CA-125 for monitoring; PIK3CA, PPP2R1A and FBXW7 mutations

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/endometrial-p53-abnormal/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/endometrial-p53-abnormal/#overview [3 state-of-the-art points]
- Types and stages (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/endometrial-p53-abnormal/#what-it-is [7 subtypes]
- Symptoms and diagnosis (on the hub): How this cancer shows itself, how the diagnosis is confirmed, and the biomarkers clinicians test for. https://onco.cc/cancers/endometrial-p53-abnormal/#finding-it [6 biomarkers]
- Treatment (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/endometrial-p53-abnormal/#treating-it [4 settings, 4 decisions with options]
- Trials and papers (on the hub): Trials recruiting now, the landmark trials, the trials held by this cancer's subtypes, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/endometrial-p53-abnormal/#evidence [6 trials, 6 key papers, 6 milestones]
- Biology and targets (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/endometrial-p53-abnormal/#science [8 targets]
- Countries and centres (own page): Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes. https://onco.cc/cancers/endometrial-p53-abnormal/where-you-are/
- Decisions and support (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/endometrial-p53-abnormal/#living-with-it [19 questions, 6 red cards]
- Pipeline and open problems (own page): Everything in development, the medicines held by this cancer's subtypes, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/endometrial-p53-abnormal/coming/ [8 medicines, 3 trials, 1 idea, 3 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/endometrial-p53-abnormal/data/ [55 connected records]

## Standard of care

- Surgery and staging: Hysterectomy with bilateral salpingo-oophorectomy, sentinel node mapping and omental sampling, with peritoneal assessment because serous tumours spread like ovarian cancer. ([Hysterectomy](https://onco.cc/terms/hysterectomy/), [Sentinel lymph node biopsy](https://onco.cc/technologies/sentinel-node/), [Robotic & minimally invasive surgery](https://onco.cc/technologies/robotic-surgery/), [Histopathology & immunohistochemistry](https://onco.cc/technologies/histopathology-ihc/))
- Adjuvant, stage I to III: Carboplatin-paclitaxel chemotherapy, with pelvic radiotherapy and vaginal brachytherapy as in PORTEC-3; chemotherapy is recommended for all p53-abnormal tumours with myometrial invasion. ([PORTEC-3](https://onco.cc/trials/portec-3/), [Carboplatin](https://onco.cc/drugs/carboplatin/), [Paclitaxel / nab-paclitaxel](https://onco.cc/drugs/paclitaxel/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [Brachytherapy](https://onco.cc/technologies/brachytherapy/), [TP53](https://onco.cc/targets/tp53/))
- Advanced or recurrent HER2-positive serous: Trastuzumab added to carboplatin-paclitaxel and continued as maintenance; trastuzumab deruxtecan for HER2-expressing disease after chemotherapy (DESTINY-PanTumor02). ([Trastuzumab](https://onco.cc/drugs/trastuzumab/), [Trastuzumab deruxtecan](https://onco.cc/drugs/trastuzumab-deruxtecan/), [DESTINY-PanTumor02](https://onco.cc/trials/destiny-pantumor02/), [HER2](https://onco.cc/targets/her2/))
- Advanced or recurrent HER2-negative: Carboplatin-paclitaxel with dostarlimab or pembrolizumab as for other endometrial cancers, though the immunotherapy gain is smaller in mismatch-repair-proficient disease; lenvatinib-pembrolizumab after platinum. ([Carboplatin](https://onco.cc/drugs/carboplatin/), [Paclitaxel / nab-paclitaxel](https://onco.cc/drugs/paclitaxel/), [Dostarlimab](https://onco.cc/drugs/dostarlimab/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [RUBY / ENGOT-EN6 / GOG-3031](https://onco.cc/trials/ruby/), [KEYNOTE-775 / Study 309](https://onco.cc/trials/keynote-775/))

## State of the art

- PORTEC-3 molecular analysis showed chemotherapy's benefit is concentrated in p53-abnormal tumours, which drives current adjuvant guidelines.
- HER2 is the first targetable driver in serous carcinoma, with trastuzumab in the first line and trastuzumab deruxtecan afterwards.
- RAINBO p53abn-RED is testing olaparib on the ovarian-cancer analogy.

## Open problems

- Distant relapse after early-stage disease despite chemotherapy.
- Whether PARP inhibition helps p53-abnormal tumours as it does ovarian cancer.
- Low response to immunotherapy in a class that accounts for most deaths.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Uterine_serous_carcinoma
- Wikipedia: https://en.wikipedia.org/wiki/Uterine_serous_carcinoma

## Connected records

- cancers: [Advanced or recurrent endometrial cancer](https://onco.cc/cancers/advanced-recurrent-endometrial-cancer/), [Endometrial cancer](https://onco.cc/cancers/endometrial/), [Endometrial cancer with no specific molecular profile](https://onco.cc/cancers/endometrial-nsmp/), [Mismatch-repair-deficient endometrial cancer](https://onco.cc/cancers/endometrial-mmr-deficient/), [POLE-ultramutated endometrial cancer](https://onco.cc/cancers/endometrial-pole-ultramutated/), [Uterine carcinosarcoma](https://onco.cc/cancers/uterine-carcinosarcoma/)
- key papers: [Carboplatin-paclitaxel with or without trastuzumab in HER2-positive advanced or recurrent uterine serous carcinoma](https://onco.cc/key-papers/paper-fader-trastuzumab-uterine-serous-jco-2018/), [Confirmation of ProMisE: a genomics-based clinical classifier for endometrial cancer](https://onco.cc/key-papers/paper-promise-talhouk-cancer-2017/), [DESTINY-PanTumor02: trastuzumab deruxtecan in HER2-expressing solid tumours](https://onco.cc/key-papers/paper-destiny-pantumor02-jco-2024/), [Integrated genomic characterisation of endometrial carcinoma (The Cancer Genome Atlas)](https://onco.cc/key-papers/paper-tcga-endometrial-nature-2013/), [Molecular classification of the PORTEC-3 trial: prognosis and benefit from adjuvant chemotherapy by molecular group](https://onco.cc/key-papers/paper-portec-3-molecular-leon-castillo-jco-2020/), [PORTEC-3: adjuvant chemoradiotherapy versus radiotherapy alone for high-risk endometrial cancer](https://onco.cc/key-papers/paper-portec-3-lancet-oncol-2018/)
- terms: [Endometrial cancer molecular classes (POLEmut, MMRd, p53abn, NSMP)](https://onco.cc/terms/endometrial-molecular-classes/), [Hysterectomy](https://onco.cc/terms/hysterectomy/)
- targets: [ATR](https://onco.cc/targets/atr/), [HER2](https://onco.cc/targets/her2/), [TP53](https://onco.cc/targets/tp53/), [WEE1](https://onco.cc/targets/wee1/)
- trials: [DESTINY-Endometrial01: A Phase III Study of Trastuzumab Deruxtecan Plus Rilvegostomig or Pembrolizumab as First-Line Treatment of HER2-Expressing (IHC](https://onco.cc/trials/nct06989112/), [DESTINY-PanTumor02](https://onco.cc/trials/destiny-pantumor02/), [KEYNOTE-775 / Study 309](https://onco.cc/trials/keynote-775/), [PORTEC-3](https://onco.cc/trials/portec-3/), [RUBY / ENGOT-EN6 / GOG-3031](https://onco.cc/trials/ruby/), [The Evaluation of PC14586 in Patients With Advanced Solid Tumors Harboring a TP53 Y220C Mutation (PYNNACLE)](https://onco.cc/trials/nct04585750/)
- drugs: [Carboplatin](https://onco.cc/drugs/carboplatin/), [Dostarlimab](https://onco.cc/drugs/dostarlimab/), [Olaparib](https://onco.cc/drugs/olaparib/), [Paclitaxel / nab-paclitaxel](https://onco.cc/drugs/paclitaxel/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Sacituzumab tirumotecan](https://onco.cc/drugs/sacituzumab-tirumotecan/), [Trastuzumab](https://onco.cc/drugs/trastuzumab/), [Trastuzumab deruxtecan](https://onco.cc/drugs/trastuzumab-deruxtecan/)
- ideas: [HER2 ADCs as standard for HER2-positive serous endometrial cancer](https://onco.cc/ideas/idea-her2-adc-serous-endometrial/)
- technologies: [Brachytherapy](https://onco.cc/technologies/brachytherapy/), [Histopathology & immunohistochemistry](https://onco.cc/technologies/histopathology-ihc/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [Robotic & minimally invasive surgery](https://onco.cc/technologies/robotic-surgery/), [Sentinel lymph node biopsy](https://onco.cc/technologies/sentinel-node/)
- people: [Amanda Nickles Fader](https://onco.cc/people/amanda-fader/)
- biomarkers: [TP53 mutation and del(17p)](https://onco.cc/biomarkers/tp53-del17p/)

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JSON: https://onco.cc/api/v1/entities/endometrial-p53-abnormal.json