Efficacy of liquid‐based genetic diagnosis of endometrial cancer

摘要

Although liquid‐based cytology (LBC) has increased the sensitivity of cytological diagnosis of endometrial cancer (EC) compared with conventional smear cytology, the sensitivity of LBC for the detection of EC is between 70% and 96% and remains unsatisfactory. In the present study, we compared the efficacy of LBC with liquid‐based genetic diagnosis (LBGDx) by amplicon sequencing of five genes including PTEN,PIK3CA,CTNNB1,KRAS, and TP53 in 48 LBC subjects who underwent endometrial screening. Consequently, LBC classified 15 samples as “positive or suspicious for malignancy” and the 15 were later confirmed as EC. However, LBC failed to identify five cases who were diagnosed as style="fixed-case">EC by additional transvaginal ultrasound and endometrial curettage, indicating that the sensitivity of cytology alone was 75% (15/20). style="fixed-case">LBGDx identified 11 pathogenic style="fixed-case">PTEN variants in 10 subjects, six style="fixed-case">PIK3 style="fixed-case">CA variants in nine, three style="fixed-case">CTNNB1 variants in five, two style="fixed-case">KRAS variants in four, and three style="fixed-case">TP53 variants in three. Collectively, at least one pathogenic variant was identified in 19 subjects, which included 17 style="fixed-case">EC (15 endometrioid carcinoma and 2 endometrial carcinosarcomas), and one cervical adenocarcinoma. However, style="fixed-case">LBGDx did not identify any pathogenic mutations in three of the 20 style="fixed-case">EC, indicating that the sensitivity of style="fixed-case">LBGDx alone was 85% (17/20). Although five style="fixed-case">EC were negative for malignancy by style="fixed-case">LBC and three were negative for pathogenic mutations by style="fixed-case">LBGDx, the combination of style="fixed-case">LBC and style="fixed-case">LBGDx would successfully diagnose all 20 style="fixed-case">EC. These data suggested that style="fixed-case">LBGDx is a useful strategy to improve the sensitivity of screening of style="fixed-case">EC by style="fixed-case">LBC.