Efficacy of liquid‐based genetic diagnosis of endometrial cancer

Abstract

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 EC by additional transvaginal ultrasound and endometrial curettage, indicating that the sensitivity of cytology alone was 75% (15/20). LBGDx identified 11 pathogenic PTEN variants in 10 subjects, six PIK3CA variants in nine, three CTNNB1 variants in five, two KRAS variants in four, and three TP53 variants in three. Collectively, at least one pathogenic variant was identified in 19 subjects, which included 17 EC (15 endometrioid carcinoma and 2 endometrial carcinosarcomas), and one cervical adenocarcinoma. However, LBGDx did not identify any pathogenic mutations in three of the 20 EC, indicating that the sensitivity of LBGDx alone was 85% (17/20). Although five EC were negative for malignancy by LBC and three were negative for pathogenic mutations by LBGDx, the combination of LBC and LBGDx would successfully diagnose all 20 EC. These data suggested that LBGDx is a useful strategy to improve the sensitivity of screening of EC by LBC.

Next-generation sequencing analysis of endometrial screening liquid-based cytology specimens: a comparative study to tissue specimens

“…Analysis with our custom-built panel identified mutations in PTEN (79%), CTNNB1 (54%), PIK3R1 (42%), PIK3CA (58%), ARID1A (67%), and TP53 (21%) in the FFPE specimens, and these variant frequencies agree with previous reports [ 40 – 42 ]. In 9 of 10 endometrial LBC samples, genetic analysis was successfully completed with PTEN (56%), CTNNB1 (44%), PIK3R1 (33%), PIK3CA (56%), ARID1A (56%), and TP53 (33%) mutation frequencies comparable to those previously reported based on amplicon sequencing for 5 genes ( PETN, PIK3CA, CTNNB1, KRAS, and TP53 ), in which at least one pathogenic variant was identified in 17 of 20 cases (85%) [ 43 ]. Of note, a few differences in genomic profiles among different specimens from the same patients were observed.…”

Analysis by Next-Generation Sequencing Panel Covered 60 Genes and 17 Microsatellite Foci in Endometrial Screening Liquid-Based Cytology Specimens A Comparative Study to Tissue Specimens

“…Analysis with our custom-built panel identified mutations in PTEN (79%), CTNNB1 (54%), PIK3R1 (42%), PIK3CA (58%), ARID1A (67%), and TP53 (21%) in the FFPE specimens, and these variant frequencies are in good agreement with previous reports [35][36][37]. Genetic analysis using endometrial LBC samples showed a total sensitivity of 90% (9/10) with comparable mutation frequencies in PTEN (56%), CTNNB1 (44%), PIK3R1 (33%), PIK3CA (56%), ARID1A (56%), and TP53 (33%) to those previously reported based on amplicon sequencing for 5 genes (PETN, PIK3CA, CTNNB1, KRAS, and TP53) in which at least one pathogenic variant was identified in 17 of 20 cases (85%) [38]. There observed few differences in genomic profile among different specimens from the same patients.…”

Next-Generation Sequencing Analysis of Endometrial Screening Liquid-Based Cytology Specimens A Comparative Study to Tissue Specimens

“…Analysis with our custom-built panel identi ed mutations in PTEN (79%), CTNNB1 (54%), PIK3R1 (42%), PIK3CA (58%), ARID1A (67%), and TP53 (21%) in the FFPE specimens, and these variant frequencies agree with previous reports [40][41][42]. In 9 of 10 endometrial LBC samples, genetic analysis was successfully completed with PTEN (56%), CTNNB1 (44%), PIK3R1 (33%), PIK3CA (56%), ARID1A (56%), and TP53 (33%) mutation frequencies comparable to those previously reported based on amplicon sequencing for 5 genes (PETN, PIK3CA, CTNNB1, KRAS, and TP53), in which at least one pathogenic variant was identi ed in 17 of 20 cases (85%) [43]. Of note, a few differences in genomic pro les among different specimens from the same patients were observed.…”