AUTHOR=Chen Lingfeng , You Zhijie , Yu Xunbin , Wu Yijuan , Chen Xin , Lin Jie 
  
TITLE=Molecular classification of endometrial carcinoma: clinical utility of an NGS panel with targeted detection of 116 cancer-related genes
  
JOURNAL=Pathology and Oncology Research
  
VOLUME=Volume 32 - 2026
  
YEAR=2026
  
URL=https://www.por-journal.com/journals/pathology-and-oncology-research/articles/10.3389/pore.2026.1612465
  
DOI=10.3389/pore.2026.1612465
  
ISSN=1532-2807
  
ABSTRACT=BackgroundThis study aimed to evaluate the efficacy of a single-test, targeted DNA next-generation sequencing (NGS) panel in classifying endometrial carcinoma (EC) into molecular subtypes and to compare its performance with that of the established Sanger sequencing + immunohistochemistry (Sanger + IHC) molecular classification.MethodsTargeted DNA NGS was performed on 131 samples using the clinically validated AmoyDx® Comprehensive Panel, and a commercially available targeted AmoyDx EC Panel covering POLE, TP53, and MSI was used for 63 samples.ResultsThe concordance between the NGS and Sanger + IHC classifications was 93.8% (182/194 cases), with a kappa value of 0.908. The exclusion of seven discordant POLE mutations improved concordance to 97.4% (kappa = 0.962). NGS identified 30 POLE mutations compared to 23 detected by Sanger sequencing, which missed low-frequency variants. Microsatellite instability (MSI) analysis and mismatch repair (MMR) immunohistochemistry (IHC) results were highly concordant (97.9%). However, NGS-based TP53 mutation detection showed moderate agreement with the p53 IHC results (kappa = 0.688). Mutations associated with targeted therapy trials, including PTEN (76.3%), PIK3CA (50.4%), and ARID1A (35.9%), were found in 131 EC samples.ConclusionThese findings indicate that NGS-based molecular classification aligns well with Sanger + IHC molecular classification and offers higher sensitivity than Sanger sequencing, thereby improving the identification of mutations associated with targeted therapy trials. This enhances the prognosis and treatment planning for patients with advanced EC.