Evidence map›Paper›PMID 25720322›Full record

ArticleModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc2015

Refining prognosis and identifying targetable pathways for high-risk endometrial cancer; a TransPORTEC initiative.

Ellen Stelloo, Tjalling Bosse, Remi A Nout, Helen J MacKay, David N Church, Hans W Nijman, Alexandra Leary, Richard J Edmondson, Melanie E Powell, Emma J Crosbie and 5 more

Open access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 231 papers, 17 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
231citing papers in PubMed, 17 pooled it
25.3field-weighted citation impact, top 1% of its field
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

231 citing papers in PubMed, 17 syntheses or guidelines pooled it, 481 citations in OpenAlex.

  1. Pooled it
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  3. Colombian consensus for the molecular diagnosis of endometrial cancerRevista colombiana de obstetricia y ginecologia · 2024
    Guideline
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  6. Uterine carcinosarcoma vs endometrial serous and clear cell carcinoma: A systematic review and meta-analysis of survival.International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics · 2022
    Pooled it
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  8. Prognostic value of the TCGA molecular classification in uterine carcinosarcoma.International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics · 2022
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171 more citing papers are in PubMed but not listed here.

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

15 authors at 9 institutions in 5 countries.

Ellen StellooDepartment of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
Tjalling BosseDepartment of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
Remi A NoutDepartment of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands.
Helen J MacKayDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, Princess Margaret Hospital/University Health Network, University of Toronto, Toronto, ON, Canada.
David N ChurchMolecular and Population Genetics Laboratory, The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Hans W NijmanDepartment of Gynecology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Alexandra LearyDepartment of Medicine, Gynecology Unit, Gustave Roussy, Villejuif, France.
Richard J EdmondsonInstitute of Cancer Sciences, University of Manchester, St Marys Hospital, Manchester, UK.
Melanie E PowellDepartment of Clinical Oncology, Barts Health NHS Trust, London, UK.
Emma J CrosbieInstitute of Cancer Sciences, University of Manchester, St Marys Hospital, Manchester, UK.
Henry C KitchenerInstitute of Cancer Sciences, University of Manchester, St Marys Hospital, Manchester, UK.
Linda MileshkinDivision of Cancer Medicine, Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia.
Pamela M PollockInstitute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia.
Vincent T SmitDepartment of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
Carien L CreutzbergDepartment of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands.
Leiden University Medical Center · NLUniversity of Manchester · GBBarts Health NHS Trust · GBCentre for Human Genetics · GBInstitut Gustave Roussy · FRPeter MacCallum Cancer Centre · AUQueensland University of Technology · AUUniversity Medical Center Groningen · NLUniversity of Toronto · CA

Funding

Department of Health NIHR-CS-012-009
6 · The paper itself

Abstract

This study aimed to investigate whether molecular analysis can be used to refine risk assessment, direct adjuvant therapy, and identify actionable alterations in high-risk endometrial cancer. TransPORTEC, an international consortium related to the PORTEC3 trial, was established for translational research in high-risk endometrial cancer. In this explorative study, routine molecular analyses were used to detect prognostic subgroups: p53 immunohistochemistry, microsatellite instability and POLE proofreading mutation. Furthermore, DNA was analyzed for hotspot mutations in 13 additional genes (BRAF, CDKNA2, CTNNB1, FBXW7, FGFR2, FGFR3, FOXL2, HRAS, KRAS, NRAS, PIK3CA, PPP2R1A, and PTEN) and protein expression of ER, PR, PTEN, and ARID1a was analyzed. Rates of distant metastasis, recurrence-free, and overall survival were calculated using the Kaplan-Meier method and log-rank test. In total, samples of 116 high-risk endometrial cancer patients were included: 86 endometrioid; 12 serous; and 18 clear cell. For endometrioid, serous, and clear cell cancers, 5-year recurrence-free survival rates were 68%, 27%, and 50% (P=0.014) and distant metastasis rates 23%, 64%, and 50% (P=0.001), respectively. Four prognostic subgroups were identified: (1) a group of p53-mutant tumors; (2) microsatellite instable tumors; (3) POLE proofreading-mutant tumors; and (4) a group with no specific molecular profile (NSMP). In group 3 (POLE-mutant; n=14) and group 2 (microsatellite instable; n=19) patients, no distant metastasis occurred, compared with 50% distant metastasis rate in group 1 (p53-mutant; n=36) and 39% in group 4 (NSMP; P<0.001). Five-year recurrence-free survival was 93% and 95% for group 3 (POLE-mutant) and group 2 (microsatellite instable) vs 42% (group 1, p53-mutant) and 52% (group 4, NSMP; P<0.001). Targetable FBXW7 and FGFR2 mutations (6%), alterations in the PI3K-AKT pathway (60%) and hormone receptor positivity (45%) were frequently found. In conclusion, molecular analysis of high-risk endometrial cancer identifies four distinct prognostic subgroups, with potential therapeutic implications. High frequencies of targetable alterations were identified and may serve as targets for individualized treatment.

Indexed as

AdultAgedBiomarkers, TumorDNA Mutational AnalysisEndometrial NeoplasmsFemaleHumansImmunohistochemistryKaplan-Meier EstimateMiddle AgedPolymerase Chain ReactionPrognosisRisk FactorsTissue Array AnalysisBiomarkers, Tumor

Identifiers

PMID25720322
OpenAlexW2081748041

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.