Universal Molecular Testing for Endometrial Cancers: Institutional Experience and Focus on Phenotypic and…

Cohort studyInternational journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists· May 2026

Universal Molecular Testing for Endometrial Cancers: Institutional Experience and Focus on Phenotypic and Clinical Characterization of POLE-mutated Cases.

Laura Warren, Courtney Connelly, Susan J Hsiao … Marie C Smithgall

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Breast & Gynecologic PathologyCohort studyQ1IF 2.1

Universal molecular testing prevented misclassification of 4 POLE-mutated endometrial cancers.

Universal Molecular Testing for Endometrial Cancers: Institutional Experience and Focus on Phenotypic and Clinical Characterization of POLE-mutated Cases.

Laura Warren … Marie C Smithgall

International journal of gynecological pathology · May 2026 · Q1 in Pathology

Background

Molecular classification of endometrial tumors is now incorporated into the 2023 FIGO staging criteria.

Purpose

We aimed to compare the molecular and histopathologic profiles of POLEmut endometrial carcinomas with and without aggressive histopathologic features.

Methods

We reviewed the results for all cases from April 2023 to December 2024 and for cases with pathogenic POLE exonuclease domain/proofreading mutation, collected relevant molecular, clinical data, immunohistochemical, and resection histopathology if available.

n = 81

Results

4

sequencing reclassified these from p53 abnormal or MMRd to POLEmut, the favorable-prognosis subtype

n = 81

More results

Our institution began universal molecular testing for newly diagnosed endometrial cancers in April 2023.

Of 198 tested endometrial cancers, 40.9% (n=81) had no specific molecular profile, 33.8% (n=67) were p53 abnormal, 19.7% (n=39) were MMRd, and 5.6% (n=11) had POLE exonuclease domain/proofreading mutations associated with the ultramutated phenotype.

More results

At least one aggressive histopathologic feature was seen in 5/10 POLEmut cases that had resection specimens.

TP53 variants were present in 5/11 POLE specimens and were often subclonal.

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Conclusion

There was no significant difference in biomarker results, molecular variants, or clinical outcomes between cases with aggressive or nonaggressive histopathologic features.

Universal Molecular Testing for Endometrial Cancers: Institutional Experience and Focus on Phenotypic and Clinical Characterization of POLE-mutated Cases.

Universal Molecular Testing for Endometrial Cancers: Institutional Experience and Focus on Phenotypic and Clinical Characterization of POLE-mutated Cases.

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