Biological consistency and molecular heterogeneity in synchronous endometrial and ovarian carcinomas: a
Wenli Gan1, Ce Bian2, Jitong Zhao3
1Department of Gynecology and Obstetrics, Affiliated Hospital of Sichuan Nursing Vocational College (The Third People's Hospital of Sichuan Province), No. 121, Jinglong Road, Longquanyi District, Chengdu, Sichuan, China.
Background:
The 2023 International Federation of Gynecology and Obstetrics (FIGO) staging system introduced Stage IA3 to categorize a subset of synchronous endometrial and ovarian carcinomas (SEOC) with favorable outcomes. This study aims to evaluate the clinical and biological rationale of the FIGO 2023 Stage IA3 criteria by analyzing paired molecular profiles and assessing the prognostic impact of ovarian versus endometrial clinicopathological features.
Methods:
A retrospective cohort of 48 SEOC patients was evaluated and stratified into three cohorts: Group A (Stage IA3, n = 12), Group B (Advanced Concordant, n = 26), and Group C (Independent Discordant, n = 10). Survival outcomes were assessed alongside clinical interventions. Given the retrospective design, clonal relationships were assessed in a sub-cohort of 17 patients for whom complete paired immunohistochemistry (IHC) data for mismatch repair (MMR) proteins and p53 were available for both tumor sites.
Results:
Univariate analysis showed that ovarian factors, including histological grade and lymph node metastasis, were significantly associated with overall survival (OS, p < 0.01). In contrast, endometrial parameters, such as myometrial invasion (MI) depth and FIGO stage, did not show statistical significance (all p > 0.5). Group A had a 5-year OS of 90.9%, while Group B showed a 5-year OS of 95.5%, and Group C showed 70.0%. Among the 17 cases with paired IHC testing, molecular discordance was identified in 29.4% (5/17) overall, all of which occurred within the non-IA3 group, yielding a discordance rate of 38.5% (5/13 in non-IA3 group vs. 0% in Stage IA3 group). Notably, Case 29 exhibited concordant p53 mutational patterns but divergent MMR status between the endometrial and ovarian lesions.
Conclusion:
In conclusion, our preliminary findings suggest that the FIGO 2023 Stage IA3 classification defines a biologically consistent, low-risk cohort, offering a potential rationale for exploring future treatment de-escalation. Furthermore, paired molecular profiling (p53 and MMR) highlights the value of assessing tumor heterogeneity and clonal evolution for refined risk stratification. Clinical management may benefit from integrating molecular risk features to better distinguish true concordant SEOC from independent aggressive malignancies, particularly in histologically discordant cases.
