IARC 60th Anniversary - 19-21 May 2026
Session : 19/05/26 - Posters
Mutation sequencing for endometrial cancer detection in urine
ONIEVA I. 2,3, PELEGRINA B, PAVÓN-DIAZ C, LÓPEZ-QUEROL, M M. 2,4, MARTÍNEZ JM, FERNANDEZ-GONZALEZ S, BARAHONA M, M. 3,5, WEVER B. 6,7,8,9, GRIFFIOEN M, BLEEKER MCG M. 6,7, GLICKMAN A, MARINA, T CELADA-CASTRO C C. 10, DORCA E, PIJUAN L E. 12, COLAS E, LUZARRAGA AZNAR A, BONALDO G E. 13, SALAMANCA-FERNÁNDEZ E, VALENZUELA A, MÉNDEZ N E. 4,14,15,16, VIDAL A. 12,17, OCON-HERNANDEZ O. 14,15,16, ANTONIO G. 13, TORNÉ A. 10,11, STEENBERGEN R. 6,7, PONCE J. 5, MATIAS-GUIU X. 3,12,17,18, ALEMANY L. 2,4, PAYTUBI* S. 2,4, COSTAS* L. 2,4
1 Catalan Institute of Oncology / IDIBELL, Hospitalet De Llobregat, Spain; 2 Cancer Epidemiology Research Programme, Catalan Institute of Oncology. IDIBELL. , L’Hospitalet de Llobregat, Barcelona, Spain; 3 Faculty of Medicine, University of Barcelona, Barcelona, Spain; 4 Consortium for Biomedical Research in Epidemiology and Public Health - CIBERESP. Carlos III Institute of Health, Madrid, Spain; 5 Department of Gynecology, Hospital Universitari de Bellvitge, IDIBELL, Hospitalet de Llobregat, Spain; 6 Amsterdam UMC, location Vrije Universiteit Amsterdam, Department of Pathology, Amsterdam , Netherlands; 7 Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam , Netherlands; 8 Peter MacCallum Cancer Centre, Melbourne, Australia; 9 Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia; 10 Gynecologic Oncology Unit, Institute Clinic of Gynecology, Obstetrics, and Neonatology, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain; 11 Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), Barcelona, Spain; 12 Department of Pathology. Hospital Universitari de Bellvitge, IDIBELL, Hospitalet de Llobregat, Spain; 13 Department of Gynecologic Oncology, Vall Hebron University Hospital, Group of Biomedical Research in Gynecology, Vall Hebron Institute of Research (VHIR), Universitat Auto?noma de Barcelona, Barcelona, Spain; 14 University of Granada. , Granada, Spain; 15 Instituto de Investigación Biosanitaria (ibs.GRANADA), Granada , Spain; 16 Gynaecology and Obstetrics Unit, 'San Cecilio' University Hospital, E-18016 , Granada, Spain; 17 Consortium for Biomedical Research in Cancer – CIBERONC. Carlos III Institute of Health, Madrid, Spain; 18 Department of Pathology, Hospital U Arnau de Vilanova, IRBLLEIDA, Lleida, Spain
Background: Endometrial cancer is the second most common gynecologic malignancy and one of the fastest-growing tumor types in incidence over the past decade. It typically presents with postmenopausal bleeding, and the probability of cancer as the underlying cause increases with age. Current diagnostic approaches rely on pelvic ultrasound and endometrial biopsy when endometrial thickness is elevated. However, ultrasound lacks specificity, leading to unnecessary invasive procedures in healthy women. Moreover, biopsies are often inconclusive or technically challenging, requiring more invasive procedures. These limitations highlight the urgent need for accurate, non-invasive diagnostic methods. In a previous pilot study, we detected somatic mutations in urine samples from 100% of endometrial cancer cases and 5% of controls, suggesting a promising approach. The objective of this study is to validate urine-based detection of somatic mutations for distinguishing endometrial cancer patients from healthy controls in a multicenter setting.
Methods: Urine samples were collected from cases and controls across six hospitals in Spain and Amsterdam. DNA from urine supernatant was analyzed using next-generation sequencing (NGS) with molecular identifiers targeting a custom panel of 47 genes. Sequencing was performed on Illumina NovaSeq using an SP flow cell and 150 bp paired-end protocol, achieving high depth (median coverage before deduplication = 24,339X; IQR = 18,892–32,128; after deduplication = 1,507X; IQR = 1,068–2,130). Survival analyses by molecular subgroup were conducted using Kaplan-Meier curves, log-rank tests, and Cox proportional hazards models adjusted for age.
Results: To date, 355 urine samples have been analyzed (207 cases, 148 controls). One sample yielded insufficient DNA and 15 were not suitable for library preparation; therefore, 96% of samples (355/361) were successfully analyzed. Somatic mutations were detected in 78.3% (162/207) of endometrial cancer cases, with a specificity of 75.0% (111/148). Excluding variants with variant allele frequency (VAF) <2% improved specificity to 95.3% (141/148) but reduced sensitivity to 65.2% (135/207). Results were consistent across centers, though analyses are ongoing. Among women presenting with bleeding, sensitivity was 79.1% (125/158) and specificity 76.2% (83/109). Sensitivity was lowest in non-endometrioid cancers (68.8%, 33/48) and highest in MMRd tumors (85.7%, 42/49). Detection of POLE mutations in urine correlated with excellent prognosis, whereas TP53 mutations were associated with poor outcomes.
Conclusions: Urine-based analysis of somatic mutations offers a practical, non-invasive approach for detecting and molecularly classifying endometrial cancer. While enrollment and optimization efforts are ongoing, these self-collected samples show strong potential for improving early diagnosis and guiding prognostic assessment, reducing reliance on invasive procedures.