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Molecular-based classification algorithm for endometrial carcinoma categorizes ovarian endometrioid carcinoma into
Carlos Parra-Herran1,2, Jordan Lerner-Ellis2,3,4, Bin Xu1,2
1Department of Anatomic Pathology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
Summary
Ovarian endometrioid carcinomas can be classified into prognostic subgroups using molecular markers. Testing for polymerase ɛ (POLE) mutations and mismatch repair (MMR) deficiency identifies good-prognosis tumors, while p53 abnormalities indicate a worse outcome.
Area of Science:
- Gynecologic Oncology
- Molecular Pathology
- Cancer Genomics
Background:
- The Cancer Genome Atlas (TCGA) classifies endometrial carcinoma into distinct molecular subgroups.
- While p53, mismatch repair proteins (MMR), and polymerase ɛ (POLE) mutations predict outcome in endometrial cancer, their role in ovarian endometrioid carcinoma is less understood.
Purpose of the Study:
- To investigate the utility of molecular markers (p53, MMR, POLE) for classifying ovarian endometrioid carcinomas.
- To determine if these molecular subgroups correlate with patient prognosis.
Main Methods:
- Retrospective analysis of 72 surgically treated ovarian endometrioid carcinomas.
- Immunohistochemistry for p53 and MMR proteins (MLH1, MSH2, MSH6, PMS2).
- POLE exonuclease domain mutation analysis.
Main Results:
- Cases were classified as POLE mutated (10%), MMR abnormal (8%), p53 abnormal (24%), and p53 wild type (58%).
- Molecular classification significantly correlated with disease-free survival (P=0.003).
- POLE-mutated and MMR-abnormal tumors showed excellent survival; p53-abnormal tumors had significantly worse recurrence-free and overall survival.
Conclusions:
- Ovarian endometrioid carcinomas can be stratified into clinically meaningful subgroups using molecular markers.
- MMR deficiency and POLE mutations identify a subset with favorable prognosis.
- Abnormal p53 is associated with a poorer prognosis, suggesting its utility in routine evaluation for personalized medicine.
