The Application of Liquid Biopsy for the Development and Validation of a Non-Invasive Screening and Diagnosis Test for Endometrial Premalignant and Malignant Lesions: A Prospective Innovative Pilot Study
by
, , , , ,
Giuseppina Esposito
1,†
,
Giuseppe D’Angelo
1,*,†,
Luigia De Falco
2,3,
Eloisa Evangelista
2,3,
Giovanni Savarese
2,3,
Antonio Fico
2,3,
Federica Cinque
1,
Pierluigi Giampaolino
1,
Attilio Di Spiezio Sardo
1,
Giuseppe Bifulco
1 and
Luigi Della Corte
4,*
1
Department of Public Health, University of Naples Federico II, 80131 Naples, Italy
2
AMES, Polidiagnostic Strumental Centre, Srl, 80013 Naples, Italy
3
Fondazione Genetica per la Vita Onlus, 80132 Naples, Italy
4
Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, 80131 Naples, Italy
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cancers 2025, 17(7), 1078; https://doi.org/10.3390/cancers17071078
Submission received: 15 January 2025
/
Revised: 19 March 2025
/
Accepted: 20 March 2025
/
Published: 23 March 2025
(This article belongs to the Special Issue Endometrial Cancer—Diagnosis and Treatment)
Simple Summary
Endometrial cancer is a common type of cancer in women, and early detection is essential for effective treatment and improved outcomes. Traditional diagnostic methods often rely on invasive procedures, which can be uncomfortable and risky. Our research explores the use of a non-invasive method called liquid biopsy, which analyzes small fragments of tumor DNA circulating in the blood. By using advanced sequencing technologies, we were able to identify specific genetic mutations linked to endometrial cancer in a large group of patients. This approach could revolutionize how endometrial cancer is diagnosed and monitored, offering a less invasive, more precise, and patient-friendly option. Our findings lay the foundation for further development of liquid biopsy techniques, which may help doctors detect cancer earlier, tailor treatments to individual patients, and track disease progression more effectively. This study represents a step forward in making cancer diagnostics more accessible and personalized.
Abstract
Background/Objectives: Endometrial cancer (EC) is a common malignancy in developed countries, with incidence closely linked to lifestyle factors and genetic predispositions, notably Lynch syndrome. Traditional biopsy methods for diagnosis and monitoring are invasive. This study aims to develop and validate a non-invasive diagnostic method for EC using liquid biopsy, specifically examining circulating tumor DNA (ctDNA) for its potential in early detection and disease monitoring. Methods: A cohort of 63 patients with EC or atypical endometrial hyperplasia (AEH) was recruited from the Gynecological Unit of the Azienda Ospedaliera Universitaria Federico II. Plasma samples were processed to extract ctDNA, which was sequenced and analyzed for mutations. Matched tumor tissue and germline DNA were also examined to confirm mutation concordance and assess potential genetic predispositions. Results: Pathogenic mutations were identified in plasma ctDNA in 59 out of 63 cases (93%), with a 65% concordance between plasma ctDNA mutations and those found in solid tumor samples. Key mutations in genes such as PTEN, PIK3R1, and KMT2C were significantly associated with a higher tumor grade and advanced stage disease, such as myometrial infiltration. Conclusions: Liquid biopsy shows promise as a minimally invasive diagnostic and monitoring tool for EC, offering real-time insights into tumor biology. The high mutation concordance between the plasma ctDNA and tumor tissue underscores the potential of a liquid biopsy in managing EC, particularly for patients at risk of recurrence. Further longitudinal studies are needed to establish ctDNA as a standard tool in EC diagnosis and monitoring.
