One-stop molecular classification of endometrial carcinoma using comprehensive next-generation sequencing

Area of Science:

• Oncology
• Genomics
• Molecular Diagnostics

Background:

• Endometrial cancer classification traditionally relies on histology.
• Molecular profiling offers deeper insights into tumor biology and patient prognosis.
• Next-generation sequencing (NGS) provides a comprehensive approach to molecular characterization.

Purpose of the Study:

• To evaluate the feasibility of molecular classification of endometrial cancer using only NGS.
• To correlate NGS-based molecular subtypes with patient survival outcomes.
• To determine if NGS can guide clinical treatment decisions for endometrial cancer.

Main Methods:

• Retrospective analysis of paired tumor-normal sequencing data from 1021 cancer-related genes in endometrial cancer patients.
• Utilized tumor tissues or peripheral blood samples for comprehensive NGS.
• Inferred microsatellite instability (MSI) status using MSIsensor with a cutoff of 8%.

Main Results:

• Four molecular groups identified: POLE^MUT (13.3%), MSI-High (MSI-H) (20%), TP53 wild-type (TP53^WT) (45%), and TP53 mutated (TP53^MUT) (21.7%).
• TP53^MUT tumors were more frequent in serous carcinoma; TP53^WT correlated with early stage and low grade.
• The TP53^MUT group showed significantly worse disease-free survival (DFS) compared to MSI-H and TP53^WT groups.

Conclusions:

• Comprehensive NGS is a feasible and effective method for molecular classification of endometrial cancer.
• NGS-based stratification provides reliable prognostic information.
• This approach has the potential to guide personalized treatment strategies in routine clinical practice for endometrial cancer.