DNA methylation testing for endometrial cancer detection in urine, cervicovaginal self-samples and cervical scrapes.


Journal

International journal of cancer
ISSN: 1097-0215
Titre abrégé: Int J Cancer
Pays: United States
ID NLM: 0042124

Informations de publication

Date de publication:
15 07 2023
Historique:
revised: 02 03 2023
received: 09 12 2022
accepted: 03 03 2023
medline: 15 5 2023
pubmed: 14 3 2023
entrez: 13 3 2023
Statut: ppublish

Résumé

Endometrial cancer incidence is rising and current diagnostics often require invasive biopsy procedures. DNA methylation marker analysis of minimally- and non-invasive sample types could provide an easy-to-apply and patient-friendly alternative to determine cancer risk. Here, we compared the performance of DNA methylation markers to detect endometrial cancer in urine, cervicovaginal self-samples and clinician-taken cervical scrapes. Paired samples were collected from 103 patients diagnosed with stage I to IV endometrial cancer. Urine and self-samples were collected at home. All samples were tested for nine DNA methylation markers using quantitative methylation-specific PCR. Methylation levels measured in endometrial cancer patients were compared to unpaired samples of 317 healthy controls. Diagnostic performances were evaluated by univariable and multivariable logistic regression analysis, followed by leave-one-out cross-validation. Each methylation marker showed significantly higher methylation levels in all sample types of endometrial cancer patients compared to healthy controls (P < .01). Optimal three-marker combinations demonstrated excellent diagnostic performances with area under the receiver operating curve values of 0.95 (95% CI: 0.92-0.98), 0.94 (0.90-0.97) and 0.97 (0.96-0.99), for endometrial cancer detection in urine, self-samples and scrapes, respectively. Sensitivities ranged from 89% to 93% at specificities of 90% to 92%. Virtually equal performances were obtained after cross-validation and excellent diagnostic performances were maintained for stage I endometrial cancer detection. Our study shows the value of methylation analysis in patient-friendly sample types for endometrial cancer detection of all stages. This approach has great potential to screen patient populations at risk for endometrial cancer.

Identifiants

pubmed: 36912267
doi: 10.1002/ijc.34504
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

341-351

Informations de copyright

© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

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Auteurs

Birgit M M Wever (BMM)

Department of Pathology, Amsterdam UMC, location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, The Netherlands.

Rianne van den Helder (R)

Department of Pathology, Amsterdam UMC, location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, The Netherlands.
Department of Gynecologic Oncology, Center of Gynecologic Oncology Amsterdam, Antoni van Leeuwenhoek/Netherlands Cancer Institute, Amsterdam, The Netherlands.

Annina P van Splunter (AP)

Department of Pathology, Amsterdam UMC, location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, The Netherlands.

Mignon D J M van Gent (MDJM)

Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, The Netherlands.
Department of Gynecologic Oncology, Center of Gynecologic Oncology Amsterdam, Amsterdam UMC, location Amsterdam Medical Center, Amsterdam, The Netherlands.

Jenneke C Kasius (JC)

Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, The Netherlands.
Department of Gynecologic Oncology, Center of Gynecologic Oncology Amsterdam, Amsterdam UMC, location Amsterdam Medical Center, Amsterdam, The Netherlands.

Johannes W Trum (JW)

Department of Gynecologic Oncology, Center of Gynecologic Oncology Amsterdam, Antoni van Leeuwenhoek/Netherlands Cancer Institute, Amsterdam, The Netherlands.

Harold R Verhoeve (HR)

Department of Obstetrics and Gynecology, OLVG, location Oost, Amsterdam, The Netherlands.

Wilhelmina M van Baal (WM)

Department of Obstetrics and Gynecology, Flevo Hospital, Almere, The Netherlands.

Alicia Hulbert (A)

Department of Surgery, University of Illinois at Chicago College of Medicine, Chicago, Illinois, USA.

Lisanne Verhoef (L)

Department of Pathology, Amsterdam UMC, location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, The Netherlands.

Daniëlle A M Heideman (DAM)

Department of Pathology, Amsterdam UMC, location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, The Netherlands.

Birgit I Lissenberg-Witte (BI)

Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, The Netherlands.
Department of Epidemiology and Data Science, Amsterdam UMC, location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

Nienke E van Trommel (NE)

Department of Gynecologic Oncology, Center of Gynecologic Oncology Amsterdam, Antoni van Leeuwenhoek/Netherlands Cancer Institute, Amsterdam, The Netherlands.

Renske D M Steenbergen (RDM)

Department of Pathology, Amsterdam UMC, location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, The Netherlands.

Maaike C G Bleeker (MCG)

Department of Pathology, Amsterdam UMC, location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, The Netherlands.

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