Evaluation of Somatic Mutations in Urine Samples as a Noninvasive Method for the Detection and Molecular Classification of Endometrial Cancer

Purpose: Current diagnostic methods for endometrial cancer lack specificity, leading to many women undergoing invasive pro-cedures. The aim of this study was to evaluate somatic mutations in urine to accurately discriminate patients with endometrial cancer from controls. Experimental Design: Overall, 72 samples were analyzed using next-generation sequencing (NGS) with molecular identifiers tar-geting 47 genes. We evaluated urine supernatant samples from women with endometrial cancer (n = 19) and age-matched controls (n = 20). Cell pellets from urine and plasma samples from seven cases were sequenced; further, we also evaluated paired tumor samples from all cases. Finally, immunohistochemical markers for molecular profiling were evaluated in all tumor samples. Results: Overall, we were able to identify mutations in DNA from urine supernatant samples in 100% of endometrial cancers. In contrast, only one control (5%) showed variants at a variant allele frequency (VAF) & GE; 2% in the urine supernatant samples. The molecular classification obtained by using tumor samples and urine samples showed good agreement. Analyses in paired samples revealed a higher number of mutations and VAF in urine super-natants than in urine cell pellets and blood samples. Conclusions: Evaluation of somatic mutations using urine sam -ples may offer a user-friendly and reliable tool for endometrial cancer detection and molecular classification. The diagnostic per-formance for endometrial cancer detection was very high, and cases could be molecularly classified using these noninvasive and self-collected samples. Additional multicenter evaluations using larger sample sizes are needed to validate the results and understand the potential of urine samples for the early detection and prognosis of endometrial cancer.

Automated summary

This study evaluated the use of urine samples for the detection and molecular classification of endometrial cancer. Mutations in DNA from urine supernatant samples were identified in 100% of endometrial cancer cases, while only one control showed variants at a low frequency. The results suggest that urine samples may offer a user-friendly and reliable tool for endometrial cancer detection and classification.