Identification of Cancer Driver Mutations in Liquid-based Cytology Samples for the Screening of Endometrial Diseases

Background: Endometrial cancer (EC) is one of the leading causes of cancer death among women and early detection is crucial for its successful treatment. We previously showed that cytological examination combined with genetic analysis using liquid-based cytology (LBC) samples improved the diagnostic sensitivity of EC.

Methods: Among 218 individuals who underwent endometrial screening by LBC, 208 samples were analysed by cancer-panel sequencing. Excluding 13 samples with low sequence coverage, we further analysed 195 samples.

Results: Among the 195 women analysed, 39 and 15 were eventually shown to suffer from malignant endometrial and non-endometrial neoplasms, respectively. Driver mutation(s) were found in nine of the 15 cytology-negative patients with endometrial malignancy, corroborating that combination of cytological and genetic analyses should increase the sensitivity of the diagnosis of malignant endometrial neoplasms. Importantly, driver alterations were found in 32 of 125 women without malignant or premalignant diseases, which raises caution for the interpretation of genetic alterations detected in the endometrial samples. Comparison between the driver mutations in the 32 subjects and those in the 29 endometrial malignancies unveiled that the number of mutations and mutations in PTEN, CTNNB1, and TP53 may be applied for the assessment and prediction of development of EC.

Conclusions: The genetic analysis combined with liquid-based cytology is useful to improve the diagnostic sensitivity of endometrial neoplasms. However, caution must be taken when cancer-associated mutation(s) are detected in the genetic analysis. Further investigation may clarify the risk of malignant endometrial neoplasms in women with driver mutation(s).