[Comparative analysis of clinicopathological and molecular characteristics between pure ovarian endometrioid carcinoma and synchronous endometrial and ovarian endometrioid carcinoma]

Objective: To investigate the differences in clinicopathological and molecular characteristics between pure ovarian endometrioid carcinoma (POEC) and synchronous endometrial and ovarian endometrioid carcinoma (SEOEC), aiming to provide a basis for their differential diagnosis and individualized treatment. Methods: Clinical and pathological data were collected from ovarian endometrioid carcinoma patients and they were divided into POEC group (219 cases) and SEOEC group (169 cases) according to whether they had endometrioid endometrial carcinoma or not. Clinical data including the age at onset, reasons for medical consultation, maximum diameter of ovarian tumors and pathological examination results such as histologic grading of the lesions were collected. Additionally, follow-up outcomes and survival status of the patients were also recorded. Molecular subtyping results were obtained from 108 cases of POEC group and 109 cases of SEOEC group patients. Large-scale targeted sequencing using next-generation sequencing was performed on 76 POEC group samples (32 with matched peripheral blood) and 51 SEOEC group samples (46 with matched peripheral blood/normal tissue). The prognosis of POEC group and SEOEC group were analyzed. Moreover, SEOEC group were further stratified to high-risk group and low-risk group according to 2020 WHO classification of tumors and 2023 International Federation of Gynecology and Obstetrics (FIGO) staging of endometrial cancer. Results: (1) Clinicopathological characteristics: compared to the SEOEC group, POEC group patients exhibited the following characteristics: younger age at diagnosis (50.0 years vs 38.0 years, P<0.001), higher proportion presenting with typical ovarian cancer symptoms (45.7% vs 92.1%, P<0.001), higher detection rates of ovarian endometriosis (14.9% vs 56.2%, P<0.001) and uterine adenomyosis (23.0% vs 37.0%, P=0.021), higher proportion of low grade tumors (78.7% vs 95.4%, P<0.001), lower proportion of mismatch repair deficiency subtype (23.9% vs 3.7%, P<0.001). (2) Gene mutation profile: although the driver gene mutation profiles were similar between the two groups, POEC group patients had a significantly lower PTEN (22.4% vs 64.0%, P<0.001) and CTNNB1 (22.4% vs 48.0%, P=0.014) mutation rates compared to SEOEC group. Also, POEC group had a higher KRAS mutation rate than SEOEC group patients (50.0% vs 28.0%, P=0.055). (3)Prognosis: survival analysis revealed that POEC group patients had a significantly shater progression free survival time compared to the low-risk SEOEC group patients(P=0.046). However, their long-term survival outcomes (both overall survival and disease specific survival) were significantly better than those of the high-risk SEOEC group patients (P=0.018 and P=0.046, respectively). Conclusions: POEC and SEOEC represent two distinct tumor entities with significantly different clinical, pathological and molecular features. Accurate differential diagnosis is crucial for correct clinical decision-making.