Evidence map›Paper›PMID 27894751›Full record

ArticleGynecologic oncology2017

Polymerase ε (POLE) ultra-mutation in uterine tumors correlates with T lymphocyte infiltration and increased resistance to platinum-based chemotherapy in vitro.

Stefania Bellone, Eliana Bignotti, Silvia Lonardi, Francesca Ferrari, Floriana Centritto, Alice Masserdotti, Francesca Pettinella, Jonathan Black, Gulden Menderes, Gary Altwerger and 19 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in Gynecologic oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed, 2 pooled it
6.0field-weighted citation impact, top 4% 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

38 citing papers in PubMed, 2 syntheses or guidelines pooled it, 82 citations in OpenAlex.

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  6. Frontiers in oncology · 2025
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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

29 authors at 4 institutions in 2 countries.

Stefania BelloneDepartment of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, PO Box 208063, New Haven, CT 06520-8063, USA.
Eliana BignottiDepartment of Obstetrics and Gynecology, ASST Spedali Civili di Brescia, Brescia, Italy.
Silvia LonardiDepartment of Molecular and Translational Medicine, Section of Pathology, University of Brescia, Brescia, Italy.
Francesca FerrariDepartment of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, PO Box 208063, New Haven, CT 06520-8063, USA.
Floriana CentrittoDepartment of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, PO Box 208063, New Haven, CT 06520-8063, USA.
Alice MasserdottiDepartment of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, PO Box 208063, New Haven, CT 06520-8063, USA.
Francesca PettinellaDepartment of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, PO Box 208063, New Haven, CT 06520-8063, USA.
Jonathan BlackDepartment of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, PO Box 208063, New Haven, CT 06520-8063, USA.
Gulden MenderesDepartment of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, PO Box 208063, New Haven, CT 06520-8063, USA.
Gary AltwergerDepartment of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, PO Box 208063, New Haven, CT 06520-8063, USA.
Pei HuiDepartment of Pathology, Yale University School of Medicine, 333 Cedar Street, PO Box 208063, New Haven, CT 06520-8063, USA.
Salvatore LopezDivision of Gynecologic Oncology, University Campus Bio-Medico of Roma, Roma, Italy.
Christopher de HayduDepartment of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, PO Box 208063, New Haven, CT 06520-8063, USA.
Elena BonazzoliDepartment of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, PO Box 208063, New Haven, CT 06520-8063, USA.
Federica PredoliniDepartment of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, PO Box 208063, New Haven, CT 06520-8063, USA.
Luca ZammataroDepartment of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, PO Box 208063, New Haven, CT 06520-8063, USA.
Emiliano CoccoDepartment of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, PO Box 208063, New Haven, CT 06520-8063, USA.
Federico FerrariDepartment of Obstetrics and Gynecology, ASST Spedali Civili di Brescia, Brescia, Italy.
Antonella Ravaggi"Angelo Nocivelli" Institute of Molecular Medicine, University of Brescia, ASST Spedali Civili, Brescia, Italy.
Chiara Romani"Angelo Nocivelli" Institute of Molecular Medicine, University of Brescia, ASST Spedali Civili, Brescia, Italy.
Fabio FacchettiDepartment of Molecular and Translational Medicine, Section of Pathology, University of Brescia, Brescia, Italy.
Enrico SartoriDepartment of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Brescia, ASST Spedali Civili, Brescia, Italy.
Franco E OdicinoDepartment of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Brescia, ASST Spedali Civili, Brescia, Italy.
Dan-Arin SilasiDepartment of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, PO Box 208063, New Haven, CT 06520-8063, USA.
Babak LitkouhiDepartment of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, PO Box 208063, New Haven, CT 06520-8063, USA.
Elena RatnerDepartment of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, PO Box 208063, New Haven, CT 06520-8063, USA.
Masoud AzodiDepartment of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, PO Box 208063, New Haven, CT 06520-8063, USA.
Peter E SchwartzDepartment of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, PO Box 208063, New Haven, CT 06520-8063, USA.
Alessandro D SantinDepartment of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, PO Box 208063, New Haven, CT 06520-8063, USA. Electronic address: alessandro.santin@yale.edu.
Yale University · USUniversity of Brescia · ITAzienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia · ITUniversità Campus Bio-Medico · IT

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Yale Pathology Tissue Services Shared ResourceP30CA016359 · NCI · YALE UNIVERSITY · PI DAVID L RIMM · 1985 to 2026
$85.0M
Integrated genomic analysis of racial disparities in endometrial cancerU01CA176067 · NCI · YALE UNIVERSITY · PI SANTIN, ALESSANDRO D · 2014 to 2018
$1.7M
CPE Peptide-Based Nanoparticles for the Diagnosis and Therapy of Chemotherapy ResR01CA154460 · NCI · YALE UNIVERSITY · PI SANTIN, ALESSANDRO D · 2011 to 2015
$1.7M
NCATS NIH HHS UL1 TR001863NCI NIH HHS P30 CA016359NCI NIH HHS R01 CA154460NCI NIH HHS U01 CA176067
6 · The paper itself

Abstract

objectiveUp to 12% of all endometrial-carcinomas (EC) harbor DNA-polymerase-ε-(POLE) mutations. It is currently unknown whether the favorable prognosis of POLE-mutated EC is derived from their low metastatic capability, extraordinary number of somatic mutations thus imparting immunogenicity, or a high sensitivity to chemotherapy.

methodsPolymerase-chain-reaction-amplification and Sanger-sequencing were used to test for POLE exonuclease-domain-mutations (exons 9-14) 131 EC. Infiltration of CD4+ and CD8+ T-lymphocytes (TIL) and PD-1-expression in POLE-mutated vs POLE wild-type EC was studied by immunohistochemistry (IHC) and the correlations between survival and molecular features were investigated. Finally, primary POLE-mutated and POLE-wild-type EC cell lines were established and compared in-vitro for their sensitivity to chemotherapy.

resultsEleven POLE-mutated EC (8.5%) were identified. POLE-mutated tumors were associated with improved progression-free-survival (P<0.05) and displayed increased numbers of CD4+ (44.5 vs 21.8; P=0.001) and CD8+ (32.8 vs 13.5; P<0.001) TILs when compared to wild-type POLE EC. PD-1 receptor was overexpressed in TILs from POLE-mutated vs wild-type-tumors (81% vs 28%; P<0.001). Primary POLE tumor cell lines were significantly more resistant to platinum-chemotherapy in-vitro when compared to POLE-wild-type tumors (P<0.004).

conclusionsPOLE ultra-mutated EC are heavily infiltrated with CD4+/CD8+ TIL, overexpress PD-1 immune-check-point (i.e., features consistent with chronic antigen-exposure), and have a better prognosis when compared to other molecular subtypes of EC patients. POLE-mutated tumor-cell lines are resistant to platinum-chemotherapy in-vitro suggesting that the better prognosis of POLE-patients is not secondary to a higher sensitivity to chemotherapy but likely linked to enhanced immunogenicity.

Indexed as

AdultAgedAged, 80 and overAntineoplastic AgentsCarboplatinCarcinomaCD4 Lymphocyte CountCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell SurvivalDisease-Free SurvivalDNA Polymerase IIDrug Resistance, NeoplasmEndometrial NeoplasmsFemaleHumansAntineoplastic AgentsCarboplatinDNA Polymerase IIPOLE protein, humanPoly-ADP-Ribose Binding ProteinsCisplatinEndometrial carcinomaPolymerase εUterine serous papillary cancerWhole exome sequencing

Identifiers

PMID27894751
PMCPMC5183545
OpenAlexW2551163894

What OpenQuestion holds

Textmetadata
LicenceTDM
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.