Evidence map›Paper›PMID 39126895›Full record

ArticleGynecologic oncology2024

Comprehensive molecular characterization of early stage grade 3 endometrioid endometrial adenocarcinoma.

Han T Cun, Laurence Bernard, Karin Teien Lande, Barrett C Lawson, Anne-Jorunn Nesbakken, Ben Davidson, Kristina Lindemann, Bryan Fellman, Therese Sørlie, Pamela T Soliman and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Gynecologic oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Han T CunSection of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Chicago, Chicago, USA. Electronic address: hcun@uchicago.edu.
Laurence BernardDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, McGill University Health Centre, Montreal, Canada.
Karin Teien LandeDepartment of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Norwegian Radium Hospital, Oslo, Norway.
Barrett C LawsonDepartment of Pathology, University of Texas MD Anderson Cancer Center, Houston, USA.
Anne-Jorunn NesbakkenDepartment of Pathology, Oslo University Hospital, Norwegian Radium Hospital, Oslo, Norway.
Ben DavidsonDepartment of Pathology, Oslo University Hospital, Norwegian Radium Hospital, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Kristina LindemannFaculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Gynecologic Oncology, Oslo University Hospital, Norwegian Radium Hospital, Oslo, Norway.
Bryan FellmanDepartment of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, USA.
Therese SørlieDepartment of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Norwegian Radium Hospital, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Pamela T SolimanDepartment of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, USA.
Ane Gerda Zahl ErikssonFaculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Gynecologic Oncology, Oslo University Hospital, Norwegian Radium Hospital, Oslo, Norway. Electronic address: aneeri@ous-hf.no.

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DIANE BODURKA · 1985 to 2026
$290.8M
Training of Academic Gynecologic OncologistsT32CA101642 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI ANIL K SOOD, Kathleen Schmeler · 2005 to 2026
$9.2M
NCI NIH HHS P30 CA016672NCI NIH HHS T32 CA101642
6 · The paper itself

Abstract

objectiveThe treatment for stage IB grade 3 endometrioid endometrial adenocarcinoma is challenging with variable practice. Molecular characterization may help identify adjuvant therapy strategies beyond stage. We aimed to better understand the molecular features of these tumors by characterizing them by ProMisE classification, mutational signature, and commonly mutated genes.

methodsPatients with stage IB grade 3 EEC at two institutions were included. Immunohistochemistry and whole exome sequencing were performed on archival FFPE tissue sections to determine ProMisE classification. Personal Cancer Genome Reporter was used for somatic variant annotation, and mutational signatures were generated based on COSMIC single base substitution mutational signatures.

results46 patients were included with variable adjuvant treatment. Nine patients recurred (19.6%), most with extra-abdominal disease (n = 5, or 55.6%). 10 had POLE mutations (21.7%), 18 were MMR deficient (39.1%), 6 had abnormal p53 (13.0%), and 12 were p53 wildtype (26.1%). There were no recurrences in the POLE subgroup. A dominant mutational signature was identified in 38 patients: 17 SBS5 signature (44.7%), 10 SBS15 or SBS44 signature (26.3%), 7 SBS10a or SBS10b signature (18.4%), 3 SBS14 signature (7.9%), and 1 SBS40 signature (2.6%). The six patients that recurred had a SBS5 signature. Frequently mutated genes included ARID1A (n = 30, 65%), PTEN (n = 28, 61%), MUC16 (n = 27, 59%), and PIK3CA (n = 25, 54%).

conclusionsThis comprehensive evaluation found a molecularly diverse cohort of tumors, despite the same histology, stage and grade. Mutational signature SBS5 correlated with a high risk of recurrence. Further refining of endometrial cancer classification may enable more precise patient stratification and personalized treatment approaches.

Indexed as

Carcinoma, EndometrioidEndometrial NeoplasmsNeoplasm GradingNeoplasm StagingAdultAgedAged, 80 and overClass I Phosphatidylinositol 3-KinasesDNA-Binding ProteinsDNA Polymerase IIExome SequencingFemaleHumansMiddle AgedMutationNeoplasm Recurrence, LocalARID1A protein, humanClass I Phosphatidylinositol 3-KinasesDNA-Binding ProteinsDNA Polymerase IIPIK3CA protein, humanPOLE protein, humanPoly-ADP-Ribose Binding ProteinsPTEN PhosphohydrolasePTEN protein, humanTranscription FactorsTumor Suppressor Protein p53Endometrial cancerMolecular classificationMutational signatureProMisE classification

Identifiers

PMID39126895
PMCPMC11660112

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.