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Abstract
Objectives To investigate the association of molecular and pathologic factors with concurrent or recurrent ovarian disease to guide ovarian preservation in endometrioid endometrial cancer.
Methods Patients with endometrial cancer ≤50 years of age at diagnosis were grouped by elective oophorectomy versus ovarian preservation at staging (January 2010 to June 2021). Tumors were stratified by molecular sub-type and CTNNB1 mutational status with next generation sequencing and immunohistochemistry. Germline data identified patients with Lynch syndrome. Associations between molecular/pathologic features and concurrent ovarian disease in patients electing oophorectomy were compared with the Wilcoxon rank-sum and Fisher’s exact tests. Associations with isolated ovarian recurrences in patients who chose ovarian preservation were examined using survival analyses.
Results Among 317 patients with endometrial cancer who underwent bilateral oophorectomy, 27 (9%) had malignant ovarian tumors, of whom 11 (41%) had no gross ovarian involvement on intra-operative survey. For patients with sequencing, concurrent malignant ovarian tumors were diagnosed in 0/14 (0%) POLE, 2/48 (4%) copy number-low/no specific molecular profile, 10/22 (45%) microsatellite instability-high, and 3/6 (50%) copy number-low/TP53abnormal patients (p<0.001). Concurrent malignant ovarian tumors were present in 1/30 (3%) hotspot CTNNB1-mutated versus 10/60 (17%) wildtype/CTNNB1 non-hotspot mutated endometrial cancer patients (p=0.11) and 7/28 (25%) Lynch versus 7/74 (9%) non-Lynch syndrome patients (p=0.06). Concurrent malignant ovarian tumors were present in patients with higher grade endometrial cancer (5% grade 1 vs 20% grade 2 and 24% grade 3; p<0.001), present versus absent lymphovascular space invasion (20% vs 6%; p=0.004), positive versus negative pelvic washings (28% vs 7%; p=0.016), and ≥50% versus <50% myoinvasion (24% vs 7%; p=0.004). Of 103 patients who chose ovarian preservation, four had isolated ovarian recurrences (two had high-risk pathologic features and two had high-risk molecular features).
Conclusions The integration of molecular and pathologic data may improve risk stratification of pre-menopausal patients with endometrial cancer and enhance candidate selection for ovarian preservation.
- Ovarian Cancer
- Endometrium
Data availability statement
Data are available upon reasonable request. In accordance with the journal’s guidelines, we will provide our data for independent analysis by a selected team by the Editorial Team for the purposes of additional data analysis or for the reproducibility of this study in other centers if such is requested.
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Data availability statement
Data are available upon reasonable request. In accordance with the journal’s guidelines, we will provide our data for independent analysis by a selected team by the Editorial Team for the purposes of additional data analysis or for the reproducibility of this study in other centers if such is requested.
Footnotes
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Contributors Conceptualization: BMG, JM. Data curation: ERD. Formal analysis: QCZ, AI. Methodology: BMG, JM. Roles/Writing - original draft: BMG, JM. Writing - review and editing: all authors. Guarantor: JM.
Funding This research was funded in part by the NIH/NCI Cancer Center Support Grant P30 CA008748. BW is funded in part by Breast Cancer Research Foundation and Cycle for Survival grants.
Competing interests Outside the submitted work, NRA-R reports research funding paid to the institution from GRAIL. Memorial Sloan Kettering Cancer Center also has equity in GRAIL. ML reports personal fees from Medtronic, Intuitive Surgical, J&J/Ethicon, and Immunogen. BW reports research funding from Repare Therapeutics, outside of the current work. The other authors have no potential conflicts of interest to disclose.
Provenance and peer review Not commissioned; externally peer reviewed.
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