Abstract
Objectives: To assess if ProMisE classifier molecular subtypes are associated with differing survival outcomes in uterine carcinosarcoma (UCS) and compare these outcomes to endometrioid endometrial cancer (EEC) tumors. Methods: There were 2235 UCS and 6469 EEC tumors using next-generation sequencing of DNA, whole exome sequencing, and RNA. Microsatellite instability (MSI) was tested by IHC and NGS. Real-world overall survival (OS) was obtained from Caris Life Sciences database and paired with insurance claims data. Hazard ratios (HR) were calculated using the Cox proportional hazards model, and p-values were calculated using the log-rank test. Results: Of the 2235 UCS samples, 2.7 % (n = 48) were POLE mutant (MT), 7.4 % (n = 132) MSI-H, 78.2 % (n = 1402), TP53 MT, and 11.7 % (n = 210), TP53 wild type (WT). In UCS POLE MT tumors, median OS (74.8 mos; 95 % CI: 30.5-not reached [NR]; p < 0.01) was significantly longer than all other subtypes. There was no difference in median post-chemo OS between POLE MT UCS and POLE MT EEC (p = 0.75) or MSI-H UCS and MSI-H EEC (p = 0.14). TP53 MT UCS and TP53 WT UCS tumors had worse median OS compared their respective ECC subtypes (27.9 vs 35.3 mos; HR: 1.3 95 % CI (1.1–1.5); p = 0.01, 29.4 vs 70.7 mos; HR: 2.0 95 % CI (1.5–2.7); p < 0.01). HER2 negative UCS had worse post-chemo OS compared to HER2 negative EEC (32.9 vs 77 mos; HR 1.60 95 % CI (1.092–2.348); p = 0.02). Conclusion: TP53 MT is the most common molecular UCS sub-type. Overall, UCS has tiered survival according to molecular classification, which mirrors EEC survival patterns. Despite UCS being considered a more aggressive histology, POLE MT and MSI-H outcomes when comparing UCS and EEC were not statistically different.
Original language | English |
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Pages (from-to) | 89-97 |
Number of pages | 9 |
Journal | Gynecologic oncology |
Volume | 193 |
DOIs | |
State | Published - Feb 2025 |
Keywords
- HER2 negative
- HER2 positive
- Immunotherapy
- Molecular classification
- Molecular profiling
- MSI-H
- POLE
- Precision oncology
- Tiered survival
- TP53 mutated
- TP53 wildtype
- Uterine carcinosarcoma