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Uterine Cavity Lavage Mutation Analysis in Lithuanian Ovarian Cancer Patients

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Simple Summary Ovarian cancer is the most lethal gynecological malignancy. The overall survival of patients this disease had not substantially changed for several decades, mainly due to the lack of… Click to show full abstract

Simple Summary Ovarian cancer is the most lethal gynecological malignancy. The overall survival of patients this disease had not substantially changed for several decades, mainly due to the lack of early diagnosis. Type II OC is the most common and most aggressive form of OC, which mainly includes high-grade serous ovarian carcinoma (HGSOC). Our study aimed to pilot whether the detection of TP53 mutation in uterine cavity lavage can be used as a diagnostic method for type II OC. Uterine lavage technique was successfully applied to all patients, also ovarian tissue biopsy was taken. All 136 samples (90 uterine cavity lavages and 46 tissues) were sequenced using six gene panel that included genes commonly associated with ovarian and endometrial cancers (TP53, BRCA1, BRCA2, PIK3CA, KRAS, and PTEN). Our pilot study proved that ctDNA from ovarian neoplasms can be collected from uterine lavage for diagnostic needs. We revealed precise detection of TP53, BRCA1, BRCA2 in uterine lavage from HGSOC by means of NGS. However, for improved sensitivity of such test, additional disease-specific biomarkers have to be discovered. Abstract Background: Type II ovarian cancer (OC) is generally diagnosed at an advanced stage, translating into a poor survival rate. Current screening methods for OC have failed to demonstrate a reduction in mortality. The uterine lavage technique has been used to detect tumor-specific TP53 mutations from cells presumably shed from high-grade serous ovarian cancer (HGSOC). We aimed to pilot whether the detection of TP53 mutation in uterine cavity lavage can be used as a diagnostic method for HGSOC using an expanded gene panel. Methods: In this study 90, uterine lavage and 46 paired biopsy samples were analyzed using next-generation sequencing (NGS) targeting TP53 as well as five additional OC-related genes: BRCA1, BRCA2, PI3KCA, PTEN, and KRAS. Results: Uterine lavage was successfully applied to all patients, and 56 mutations were detected overall. TP53 mutations were detected in 27% (10/37) of cases of type HGSOC; BRCA1 and BRCA2 mutations were also frequent in this group (46%; 17/37). Overall concordance between tissue and liquid biopsy samples was 65.2%. Conclusion: Uterine lavage TP53 mutations in combination with other biomarkers could be a useful tool for the detection of lowly invasive HGSOC.

Keywords: uterine cavity; ovarian cancer; tp53; uterine lavage; lavage

Journal Title: Cancers
Year Published: 2023

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