p53-abnormal endometrial cancer, including uterine serous carcinoma
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.
Overview
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.
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.
Red cards
From the labels and guidelines behind the standard of care. Your team's thresholds win.- Emergency services nowBleeding or bruising
Bleeding that will not stop, black or bloody stools, or unexplained bruising when platelets are expected to be low.
- Emergency services nowHypophysitis or adrenal crisis
Persistent headache with extreme tiredness, nausea, dizziness on standing or low blood pressure. Vomiting, severe weakness or collapse is adrenal crisis.
- Emergency services nowSkin reaction
Blisters, peeling, or sores in the mouth or eyes with a rash. Enfortumab vedotin carries a boxed warning for Stevens-Johnson syndrome and toxic epidermal necrolysis, mostly in the first cycle.
- Call the 24-hour line nowInterstitial lung disease or pneumonitis
Any new or worsening cough, breathlessness or fever. The label says to interrupt treatment for any suspected ILD and to permanently discontinue for grade 2 or higher.
- Check before combiningFood and drink: Pembrolizumab
No pharmacokinetic interactions expected (antibody). See the irAE guide for toxicity management.
- Check before combiningFood and drink: Trastuzumab deruxtecan
Interstitial lung disease in 10-15%: hold for any respiratory symptom and image; permanently discontinue for grade 2 or above. Moderately emetogenic: three-drug prophylaxis.
See all on the product pages:CarboplatinDostarlimabPaclitaxel / nab-paclitaxelPembrolizumabTrastuzumab deruxtecan·Printable cards in the navigator
Anatomy and lymph node drainage
- Fallopian tube fimbria (origin of high-grade serous)
- Ovary (other histologies, germ cell)
- Endometrium
- Myometrium (uterine sarcoma)
- Placental site (gestational trophoblastic)
- Cervix, transformation zone
- Vulva
- Nodes: obturator and external iliac
- Nodes: internal iliac
- Nodes: para-aortic (ovary, high uterus)
- Nodes: inguinal (vulva)
Most high-grade ovarian cancers begin at the tip of the fallopian tube; endometrial cancer lines the uterus, cervical cancer starts at the transformation zone; each drains to a different node group.
- Fallopian tube fimbria (origin of high-grade serous)Uterine serous carcinoma (p53-abnormal in nearly all cases) · HER2-positive serous carcinoma (about a quarter to a third) · Serous endometrial intraepithelial carcinoma (precursor)
- Ovary (other histologies, germ cell)p53-abnormal grade 3 endometrioid carcinoma · p53-abnormal clear cell carcinoma
- EndometriumUterine 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)
- Myometrium (uterine sarcoma)Carcinosarcoma (biphasic, usually p53-abnormal)
- Placental site (gestational trophoblastic)
- Cervix, transformation zone
- Vulva
- obturator and external iliac
- internal iliac
- para-aortic (ovary, high uterus)
- inguinal (vulva)
Same organ: High-grade serous ovarian cancer, Low-grade serous ovarian cancer, Clear cell ovarian cancer, Mucinous ovarian cancer, Adult granulosa cell tumour of the ovary, Ovarian cancer, Endometrial cancer, Cervical cancer, Vulvar cancer, Gestational trophoblastic neoplasia, Uterine sarcoma, Vaginal cancer, POLE-ultramutated endometrial cancer, Mismatch-repair-deficient endometrial cancer, Endometrial cancer with no specific molecular profile, Advanced or recurrent endometrial cancer, Uterine carcinosarcoma, Early cervical cancer and fertility-sparing surgery, Locally advanced cervical cancer, Recurrent or metastatic cervical cancer, Platinum-sensitive ovarian cancer, Platinum-resistant ovarian cancer
Show survival figures (1)
Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
- 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.
Cases by country
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
Hysterectomy with bilateral salpingo-oophorectomy, sentinel node mapping and omental sampling, with peritoneal assessment because serous tumours spread like ovarian cancer.
Carboplatin-paclitaxel chemotherapy, with pelvic radiotherapy and vaginal brachytherapy as in PORTEC-3; chemotherapy is recommended for all p53-abnormal tumours with myometrial invasion.
Trastuzumab added to carboplatin-paclitaxel and continued as maintenance; trastuzumab deruxtecan for HER2-expressing disease after chemotherapy (DESTINY-PanTumor02).
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.
Subtypes & biomarkers
top- 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)
- 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
How often this target appears
- 1982Hendrickson describes uterine papillary serous carcinoma as a distinct aggressive type
- 2013TCGA defines the copy-number-high, serous-like class
- 2018PORTEC-3: chemoradiation plus chemotherapy improves survival in high-risk disease
- 2018Randomised phase 2: trastuzumab with carboplatin-paclitaxel improves survival in HER2-positive serous carcinoma
- 2020PORTEC-3 molecular analysis: chemotherapy benefit concentrated in p53-abnormal tumours
- 2024Trastuzumab deruxtecan approved for HER2 3+ solid tumours after DESTINY-PanTumor02
Dated changes read from the records linked to this cancer: approvals, regulatory steps, reported trials, guideline versions and milestones. Newest first; no date is inferred.
All 11 changes by month →- 2026-09-17This recordp53-abnormal endometrial cancer, including uterine serous carcinomaFacts on this page last checked
When this page itself was last checked or edited.
- 2024MilestoneTrastuzumab deruxtecanTrastuzumab deruxtecan approved for HER2 3+ solid tumours after DESTINY-PanTumor02
A milestone in how this cancer is treated.
- 2023Trial resultDESTINY-PanTumor02DESTINY-PanTumor02 reported
Endometrial ORR 57.
- 2023Trial resultRUBY / ENGOT-EN6 / GOG-3031RUBY / ENGOT-EN6 / GOG-3031 reported
OS 44.
- 2021Trial resultKEYNOTE-775 / Study 309KEYNOTE-775 / Study 309 reported
OS 18.
- 2020MilestonePORTEC-3PORTEC-3 molecular analysis: chemotherapy benefit concentrated in p53-abnormal tumours
A milestone in how this cancer is treated.
What is in development for p53-abnormal endometrial cancer, including uterine serous carcinoma, drawn from the whole corpus: 6 items. Drugs are grouped by the most advanced trial phase they have reached anywhere; approved treatments sit under standard of care. Technologies are the methods being tested for this cancer, trials are the studies recorded here, and ideas are proposals not yet in a trial.
Trials under way · 1
Trials reported · 2
- DESTINY-PanTumor02 · phase 2 · 2023 · positive
- PORTEC-3 · phase 3 · 2018 · positive
Targets under investigation · 2
Ideas not yet in a trial · 1
Open problems and what is being done
Distant relapse after early-stage disease despite chemotherapy.
and how the field plans to fix it →What is being done about thisAdvanced and metastatic diseaseAvailable now- IMRT / IGRT (modern external beam)Standard of care
- Sentinel lymph node biopsyStandard of care
- Trastuzumab deruxtecanApproved
In trialsNothing recorded yet.
Ideas and roadmapsNothing recorded yet.
Also on OnCo: Atlas of advanced disease · Invasion and metastasis.
Whether PARP inhibition helps p53-abnormal tumours as it does ovarian cancer.
Low response to immunotherapy in a class that accounts for most deaths.
Trials
topTrials recruiting now
Country and place are remembered in this browser only. A postcode is sent to OpenStreetMap's Nominatim service to find coordinates when you press the button; nothing else leaves your device.
Landmark trials
Expert centres
topExpert centres
New York · cancer center | United States | 0 | 5,100 | 94,456 | #1 | ||
Villejuif · cancer center | France | none recorded | 0 | 1,855 | 31,182 | #6 | |
London · cancer center | United Kingdom | none recorded | 0 | 1,026 | 17,745 | #7 | |
Baltimore · cancer center | United States | 0 | 2,955 | 41,449 | #10 | ||
Milan · cancer center | Italy | none recorded | 0 | 1,246 | 21,746 | #11 | |
Tokyo · government | Japan | none recorded | 0 | 1,599 | 21,937 | none recorded | #13 |
Seoul · hospital | South Korea | none recorded | 0 | 464 | 3,248 | #22 | |
Beijing · cancer center | China | none recorded | 0 | 371 | 4,070 | none recorded | #50 |
Philadelphia, PA · consortium | United States | none recorded | 1 | 165 | 1,237 | - | |
Newcastle, NSW · consortium | Australia | none recorded | 1 | 34 | 760 | - | |
Chicago, IL · consortium | United States | none recorded | 1 | not matched | - | - | |
Shanghai · hospital | China | none recorded | 0 | 2,872 | 31,534 | - | |
Sydney · cancer center | Australia | none recorded | 0 | 2,222 | 33,278 | - | |
Los Angeles · cancer center | United States | 0 | 2,019 | 32,934 | - | ||
Beijing · hospital | China | none recorded | 0 | 1,784 | 18,230 | - |
These are the things we can measure; they are not a ranking of quality. Each column is a field on the institution record or a count over what OnCo has linked; a centre that treats many patients with p53-abnormal endometrial cancer, including uterine serous carcinoma but is thinly recorded here will look small.
Not known: OnCo holds no case-volume or outcome figures for centres, so none are shown. Where a national audit or registry publishes them, the centre's page links to it. Default order: Newsweek rank, then trials for this cancer, then research output.
Questions to ask
topQuestions to ask your oncologist about p53-abnormal endometrial cancer, including uterine serous carcinoma
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Why: Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example p53 immunohistochemistry, TP53 sequencing where staining is equivocal, HER2 immunohistochemistry and in situ hybridisation, Copy-number burden and homologous recombination deficiency, CA-125 for monitoring), and what were the results?Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Why: Recognised subtypes for this cancer include Uterine serous carcinoma, HER2-positive serous carcinoma, Serous endometrial intraepithelial carcinoma.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
Surgery and staging
- For my situation (surgery and staging), which of the standard options do you recommend and why?Why: Guideline options include: Hysterectomy with bilateral salpingo-oophorectomy, sentinel node mapping and omental sampling, with peritoneal assessment because serous tumours spread like ovarian cancer.
Adjuvant, stage I to III
- For my situation (adjuvant, stage i to iii), which of the standard options do you recommend and why?Why: Guideline options include: Carboplatin-paclitaxel chemotherapy, with pelvic radiotherapy and vaginal brachytherapy as in PORTEC-3; chemotherapy is recommended for all p53-abnormal tumours with myometrial invasion.
- Am I a candidate for Carboplatin, Paclitaxel / nab-paclitaxel, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of PORTEC-3 apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Advanced or recurrent HER2-positive serous
- For my situation (advanced or recurrent her2-positive serous), which of the standard options do you recommend and why?Why: Guideline options include: Trastuzumab added to carboplatin-paclitaxel and continued as maintenance; trastuzumab deruxtecan for HER2-expressing disease after chemotherapy (DESTINY-PanTumor02).
- Am I a candidate for Trastuzumab, Trastuzumab deruxtecan, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of DESTINY-PanTumor02 apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Advanced or recurrent HER2-negative
- For my situation (advanced or recurrent her2-negative), which of the standard options do you recommend and why?Why: Guideline options include: 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.
- Am I a candidate for Carboplatin, Paclitaxel / nab-paclitaxel, Dostarlimab or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of RUBY / ENGOT-EN6 / GOG-3031 and KEYNOTE-775 / Study 309 apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Any stage
- Are there clinical trials I could join, for example of DESTINY-Endometrial01: A Phase III Study of Trastuzumab Deruxtecan Plus Rilvegostomig or Pembrolizumab as First-Line Treatment of HER2-Expressing (IHC, Trastuzumab deruxtecan, Olaparib, HER2 ADCs as standard for HER2-positive serous endometrial cancer?Why: Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Why: Supportive care improves quality of life and helps patients complete treatment.
- I read that “Distant relapse after early-stage disease despite chemotherapy”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “Whether PARP inhibition helps p53-abnormal tumours as it does ovarian cancer”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
Newly diagnosed? Read the first 60 days with p53-abnormal endometrial cancer, including uterine serous carcinoma, then print the one-page appointment sheet with room for the answers.
Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.
Direct links plus the targets, companies, and technologies of this cancer's products.
technologies
12targets
8drugs
8companies
9terms
2trials
5ideas
1Latest papers
topQuery for this cancer: (TITLE:"p53-abnormal endometrial cancer, including uterine serous carcinoma" OR ABSTRACT:"p53-abnormal endometrial cancer, including uterine serous carcinoma" OR TITLE:"p53abn endometrial cancer" OR ABSTRACT:"p53abn endometrial cancer" OR TITLE:"Copy-number-high endometrial cancer" OR ABSTRACT:"Copy-number-high endometrial cancer" OR TITLE:"Uterine serous carcinoma" OR ABSTRACT:"Uterine serous carcinoma" OR TITLE:"Uterine papillary serous carcinoma" OR ABSTRACT:"Uterine papillary serous carcinoma" OR TITLE:"Serous-like endometrial cancer" OR ABSTRACT:"Serous-like endometrial cancer") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about p53-abnormal endometrial cancer, including uterine serous carcinoma, not a curated reading list.
Similar pages
not linked directly; found by shared links- CancerUterine carcinosarcoma
Shares HER2 ADCs as standard for HER2-positive serous endometrial cancer, Hysterectomy, DESTINY-PanTumor02, PORTEC-3 and the tag subtype-page.
- CancerEndometrial cancer with no specific molecular profile
Shares KEYNOTE-775 / Study 309, Hysterectomy, Endometrial cancer molecular classes (POLEmut, MMRd, p53abn, NSMP), PORTEC-3 and the tag subtype-page.
- CancerPOLE-ultramutated endometrial cancer
Shares Hysterectomy, Endometrial cancer molecular classes (POLEmut, MMRd, p53abn, NSMP), PORTEC-3, Dostarlimab and the tag subtype-page.
- CancerAdvanced or recurrent endometrial cancer
Shares KEYNOTE-775 / Study 309, DESTINY-Endometrial01: A Phase III Study of Trastuzumab Deruxtecan Plus Rilvegostomig or Pembrolizumab as First-Line Treatment of HER2-Expressing (IHC, DESTINY-PanTumor02, RUBY / ENGOT-EN6 / GOG-3031 and the tag subtype-page.
- CancerMismatch-repair-deficient endometrial cancer
Shares Hysterectomy, Endometrial cancer molecular classes (POLEmut, MMRd, p53abn, NSMP), PORTEC-3, RUBY / ENGOT-EN6 / GOG-3031 and the tag subtype-page.
- CancerRecurrent or metastatic cervical cancer
Shares DESTINY-PanTumor02, Sacituzumab tirumotecan, Robotic & minimally invasive surgery, Trastuzumab deruxtecan and the tag subtype-page.
- CancerEarly cervical cancer and fertility-sparing surgery
Shares Hysterectomy, Sentinel lymph node biopsy, Brachytherapy, Robotic & minimally invasive surgery and the tag subtype-page.
- CancerMucinous ovarian cancer
Shares Trastuzumab, Trastuzumab deruxtecan, HER2, Carboplatin and the tag subtype-page.