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Prognostic Stratification of Multiple-Classifier Endometrial Cancers: Cohort Study and Meta-Analysis.
Sabrina Paratore1, Angela Russo1, Katia Lanzafame2
1Pathological Anatomy Unit, Department of Oncology, ARNAS Garibaldi Hospital, 95122 Catania, Italy.
Cancers
|March 28, 2026
Summary
Endometrial carcinoma (EC) with multiple molecular classifiers presents a challenge to current systems. These rare tumors are biologically diverse, necessitating standardized testing for improved risk stratification and patient management.
Area of Science:
- Oncology
- Genomics
- Pathology
Background:
- Molecular classification has improved prognostic stratification in endometrial carcinoma (EC).
- A subset of ECs with multiple molecular classifiers challenges existing hierarchical systems.
- The biological and clinical significance of these multiple-classifier ECs is not fully understood.
Purpose of the Study:
- To investigate the biological and clinical significance of multiple-classifier ECs.
- To compare multiple-classifier ECs with single-classifier tumors.
- To estimate the incidence and distribution of multiple-classifier ECs through meta-analysis.
Main Methods:
- Analysis of 150 EC patients using next-generation sequencing and immunohistochemistry.
- Integration of molecular and clinicopathological data.
- Systematic review and meta-analysis of existing studies and the current cohort.
Main Results:
- 6% of ECs in the cohort exhibited multiple molecular classifiers.
- POLEmut-MMRd/MSI tumors showed favorable features, while MMRd/MSI-p53abn/TP53mut tumors had adverse features.
- Meta-analysis revealed an overall prevalence of ~5.4% for multiple-classifier ECs, with significant heterogeneity.
Conclusions:
- Multiple-classifier ECs are a small but clinically relevant subset with diverse biology.
- Current molecular classification hierarchies have limitations in classifying these tumors.
- Harmonized molecular testing and standardized reporting are crucial for improved EC risk stratification and management.
