Application of NGS molecular classification in the diagnosis of endometrial carcinoma: A supplement to traditional pathological diagnosis

Abstract

Objective: This study aims to demonstrate the advantages of NGS molecular classification in EC diagnosis and to assess whether molecular classification could be performed on curettage specimens and its concordance with subsequent hysterectomy specimens.Methods: 80 patients with hysterectomy specimens and 35/80 patients with paired curettage specimens were stratified as POLE mut, MSI-H, TP53 wt, or TP53 abn group by NGS panel. Histotype, tumor grade, IHC results, and other pathological details were taken from original pathological reports. Results:The correlation analysis of 80 patients with hysterectomy specimens between NGS molecular classification and clinicopathological characters displayed that the POLE mut group was associated with EEC (87.5%) and TP53 abn subtype was correlated to a later stage (Stage II-IV, 47.6%), G3 (76.2%), serous histology (61.9%) and myometrial invasion ≥50% (47.6%). A favorable concordance (31/32, 96.9%) was shown in MSI analysis and MMR IHC results, and the agreement rate of p53 IHC and TP53 mutation was 81.5% (53/65). Compared with the p53 IHC abnormal group, the TP53 mutation group had a higher correlation with highrisk factors. A high level of concordance (31/35, 88.0%) of NGS molecular classification was achieved between curettage specimens and hysterectomy specimens while grade and histotype (including unclassified group) from curettage specimens and hysterectomy specimens showed only moderate levels of agreement, 54.3% (19/35) and 68.6% (24/35), respectively. Conclusion: NGS molecular classification achieved on curettage samplesshowed high concordance with the final hysterectomy specimens, demonstrating superior to the conventional pathological assessment of grade and histotype and potential utilization in clinical practice. | METHODS | Patient cohort, sample collection, and pathological information collectionThe study consists of a retrospective cohort of patients with EC from Sun Yat-Sen Memorial Hospital, Sun Yat-Sun University treated for EC between 2018 and 2021.

Clinical application of FIGO 2023 staging system of endometrial cancer in a Chinese cohort

“…Previous studies, including the ProMisE and TransPORTEC classi ers, have suggested that p53, MLH1, MSH2, MSH6, and PMS2 protein immunostaining status as a substitute for TP53 NGS and microsatellite instability status [3,22], with an approximate accuracy range of 81.3%-95.6% and 93.3%-98.8% [23][24][25][26], respectively. We also employed the IHC as an alternative to molecular testing for economic practicality and clinical accessibility.…”

New online dynamic nomograms: recurrence-free and overall survival after resection of endometrial cancer

“…Second, the prognostic signi cance of OS was not entirely accurate because data that may affect patient survival, such as chemotherapy, radiotherapy, and surgery, were excluded from the nomogram. Moreover, next generation sequencing molecular classi cation has demonstrated superiority over conventional pathological assessment of grade and histotype (37). Future modeling should consider these factors.…”

Outcomes of fertility preservation treatments in patients with endometrial cancer with different molecular classifications based on an NGS panel

“…Subsequently, clinically applicable molecular classification systems were developed based on immunohistochemistry (IHC) or next generation sequencing (NGS) (9)(10)(11)(12). NGS has been established to represent an effective method for the molecular classification of EC and shows high concordance with the final hysterectomy specimens when applied to curettage samples (13). According to NGS molecular classification, EC can be divided into four subtypes: (1) POLE mutated (POLE mut), (2) microsatellite instability hypermutated (MSI-H), 3.…”