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© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Objectives: The purpose of the study is to determine whether FOXL2 circulating tumor DNA can be used as a prognostic biomarker and marker for monitoring treatment response in patients with an adult-type granulosa cell tumor (aGCT). Methods: Plasma samples of patients included in the multicenter GRANULOSA study were collected before and after surgery for primary or recurrent aGCT, during follow-up, and during systemic treatment. The presence of ctDNA containing the FOXL2 402C>G mutation was analyzed in 284 samples from 20 primary and 34 recurrent aGCT patients, using digital droplet PCR. Clinical data were retrieved from electronic patient records, and patients were followed through January 2025. Results: FOXL2 mutant ctDNA was detected in 28 of 54 patients (48%). In primary aGCT, recurrences were more frequently seen in patients with detectable ctDNA (33% vs. 18%), and ctDNA remained detectable postoperatively in some cases despite complete cytoreduction. In recurrent aGCT patients, detectable ctDNA was associated with significantly worse overall survival (p = 0.023), and the postoperative presence of ctDNA following complete debulking surgery was significantly associated with a shorter recurrence-free survival (4.7 vs. 11.6 months, p = 0.025). Conclusions: FOXL2 mutant ctDNA could be a prognostic biomarker in aGCT, being associated with worse overall survival in recurrent aGCT patients. In addition, the presence of ctDNA after surgery could reflect the presence of minimal residual disease, negatively impacting the disease course. The implementation of FOXL2 ctDNA measurement in clinical practice may help to identify high-risk aGCT patients.

Details

Title
The Prognostic Value of FOXL2 Mutant Circulating Tumor DNA in Adult Granulosa Cell Tumor Patients
Author
Brink, Geertruid J 1   VIAFID ORCID Logo  ; Hami Nizar 2 ; Nijman, Hans W 3   VIAFID ORCID Logo  ; Piek Jurgen M. J. 4   VIAFID ORCID Logo  ; van Lonkhuijzen Luc R. C. W. 5   VIAFID ORCID Logo  ; Roes, Eva Maria 6 ; Ward, Hofhuis 7 ; Lok, Christianne A, R 8   VIAFID ORCID Logo  ; de Kroon Cor D. 9   VIAFID ORCID Logo  ; Gort, Eelke H 10 ; Witteveen, Petronella O 10   VIAFID ORCID Logo  ; Zweemer, Ronald P 1   VIAFID ORCID Logo  ; Groeneweg Jolijn W. 1   VIAFID ORCID Logo 

 Department of Gynecologic Oncology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands 
 Department of Molecular Cancer Research, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands 
 Department of Obstetrics and Gynecology, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands 
 Department of Obstetrics and Gynecology, Catharina Hospital, 5623 EJ Eindhoven, The Netherlands 
 Center for Gynecologic Oncology Amsterdam, Cancer Center Amsterdam, Amsterdam University Medical Center, 1105 AZ Amsterdam, The Netherlands 
 Department of Gynecologic Oncology, Erasmus MC Cancer Institute, 3015 GD Rotterdam, The Netherlands 
 Department of Obstetrics and Gynecology, Franciscus Gasthuis en Vlietland, 3045 PM Rotterdam, The Netherlands 
 Department of Gynecological Oncology, Center Gynaecologic Oncology Amsterdam, 1066 CX Amsterdam, The Netherlands 
 Department of Gynecology, Leiden University Medical Center, 2333 ZG Leiden, The Netherlands 
10  Department of Medical Oncology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands 
First page
1894
Publication year
2025
Publication date
2025
Publisher
MDPI AG
e-ISSN
20726694
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3217719825
Copyright
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.