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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.
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.
Averages across everyone diagnosed, often years ago. A median is the middle of a group: half the people counted lived longer than the figure shown, and some lived far longer. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
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.
Same organ: Adenosquamous carcinoma of the cervix, Small cell neuroendocrine carcinoma of the cervix, Bartholin gland carcinoma, Vulvar melanoma, Vaginal melanoma, 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, HPV-associated vulvar squamous cell carcinoma, HPV-independent vulvar squamous cell carcinoma (p53-mutant), Vaginal squamous cell carcinoma (HPV-associated), Vaginal adenocarcinoma (including DES-associated clear cell adenocarcinoma), Low-risk gestational trophoblastic neoplasia (FIGO score 0 to 6), High-risk gestational trophoblastic neoplasia (FIGO score 7 or more, including ultra-high-risk), Placental-site trophoblastic tumour and epithelioid trophoblastic tumour
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.
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HER2 immunohistochemistry is now worth doing in advanced gynaecological and other cancers, since trastuzumab deruxtecan is approved for HER2 3+ solid tumours after prior therapy.
Molecular class is now a predictive factor for adjuvant therapy: chemotherapy for p53-abnormal disease, de-escalation for POLE-mutated tumours, and trials of immunotherapy for mismatch repair-deficient disease.
HER2 testing of every serous endometrial cancer and trastuzumab with first-line chemotherapy for HER2-positive advanced disease are now guideline recommendations; trastuzumab deruxtecan extends the option.
Chemoradiotherapy is the standard for stage III and for p53-abnormal or serous endometrial cancer; for other stage I to II tumours radiotherapy alone or brachytherapy suffices.
Molecular classification of every endometrial cancer, now embedded in the WHO classification and the ESGO/ESTRO/ESP guideline, rests on ProMisE; it decides adjuvant therapy and identifies candidates for immunotherapy.
This is the origin of the molecular classification now used for every endometrial cancer, translated into a practical test by ProMisE.
Query 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.
The targets of this cancer's medicines and the ones linked to it directly.
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.
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Bleeding that does not stop by itself, bleeding from more than one site, or new bruising in several places or one large area.
Persistent headache with extreme tiredness, nausea, dizziness on standing or low blood pressure. Vomiting, severe weakness or collapse is adrenal crisis.
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.
Temperature of 38 C or higher, or feeling shivery and unwell even without a fever. Antibody-drug conjugates suppress the bone marrow, and several carry a boxed warning for severe neutropenia.
No pharmacokinetic interactions expected (antibody). See the irAE guide for toxicity management.
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
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