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Variability in endometrial carcinoma pathology practice: opportunities for improvement with molecular classification
Emily F Thompson1, Jutta Huvila1,2, Amy Jamieson3
1Department of Molecular Oncology, University of British Columbia, Vancouver, BC, Canada.
Summary
Molecular subtyping of endometrial cancer (EC) reveals significant practice gaps in biomarker testing. Standardizing molecular classification improves patient management and diagnostic consistency for better outcomes.
Area of Science:
- Oncology
- Pathology
- Genomics
Background:
- Endometrial cancer (EC) management can be improved by molecular classification.
- Diagnostic pathology practices for EC in Canada in 2016 showed significant variability.
- Molecular subtyping (POLEmut, MMRd, p53abn, NSMP) impacts patient outcomes.
Purpose of the Study:
- To assess the current landscape of diagnostic pathology practice for endometrial cancer.
- To evaluate the impact of molecular classification on patient management.
- To identify opportunities for improving biomarker testing and reporting.
Main Methods:
- Retrospective analysis of 1357 endometrial cancer patient samples from Canadian centers.
- Assignment of ProMisE molecular subtypes: POLEmut, Mismatch Repair Deficient (MMRd), p53 abnormal (p53abn), and No Specific Molecular Profile (NSMP).
- Evaluation of Immunohistochemistry (IHC) usage for MMR and p53 proteins at diagnosis.
Main Results:
- Only 42% of cases had MMR IHC and 21.1% had p53 IHC performed in 2016.
- Significant proportions of MMRd (54.7%) and p53abn (48.2%) ECs were not tested for the respective biomarkers.
- Molecular subtype was significantly associated with clinical outcomes, including in stage I disease.
Conclusions:
- Diagnostic pathology practice for EC in 2016 demonstrated highly variable use of essential biomarkers (MMR, p53 IHC).
- Inconsistent testing led to missed opportunities for hereditary cancer referrals, Lynch Syndrome diagnosis, and targeted therapies.
- Routine integration of molecular subtyping is crucial for consistent EC assessment, classification, and improved patient care.
