Distinct endometriosis involvement confers divergent oncologic outcomes in ovarian clear cell carcinoma

Archives of Gynecology and Obstetrics https://doi.org/10.1007/s00404-025-08025-3 RESEARCH Distinct endometriosis involvement confers divergent oncologic outcomes in ovarian clear cell carcinoma Jie Deng1,2 · Jiayuan Li3 · Lian Xu4 · Tianjin Yi1 Received: 4 November 2024 / Accepted: 31 March 2025 © The Author(s) 2025 Abstract Objective To evaluate the clinicopathologic characteristics and survival outcomes of ovarian clear cell carcinoma (OCCC) patients with different endometriosis statuses. Methods This retrospective study included OCCC patients diagnosed between 2012 and 2021, classified into three groups based on the Sampson and Scott criteria: Without (no endometriosis), Arising (OCCC arising from endometriosis), and Coexisting (OCCC coexisting with endometriosis). Clinical and pathological characteristics were compared across groups, and survival outcomes were analyzed using Kaplan–Meier methods. Prognostic factors for progression-free survival (PFS) and overall survival (OS) were identified through univariate and multivariate analyses. Results Among 242 patients, 53.7% were in the Without group, 29.3% in the Arising group, and 16.9% in the Coexisting group. The Arising group had the highest prevalence of early FIGO stage disease (91.6%) compared to the Coexisting (75.6%, p = 0.041) and Without (67.7%, p = 0.000) groups. Lymph-node metastasis was significantly lower in the Arising group (2.8%) than in the Coexisting (19.5%, p = 0.010) and Without (10%, p = 0.011) groups. Notably, the Arising group demonstrated unique atypical endometriosis features. In univariate analysis, the presence of endometriosis (either arising from or coexisting with endometriosis) was associated with improved PFS (p = 0.004 and p = 0.009, respectively); however, multivariate analysis confirms only coexisting with endometriosis as an independent factor (HR: 0.11, 95% CI: 0.01–0.84). For OS, the Arising group demonstrated the most significant benefit, with a 5-year OS of 92.4% compared to the Coexisting group (83.9%, p = 0.293) and the Without group (62.6%, p = 0.023). Multivariate analysis identified only FIGO stage (HR: 5.89, 95% CI: 2.06–16.82) as an independent prognostic factor for OS, while endometriosis did not reach statistical significance (HR: 0.62, 95% CI: 0.26–1.53). Conclusions Classifying OCCC with endometriosis statuses reveals distinct prognostic patterns. Coexisting with endometriosis positively impacts PFS, while the Arising subgroup shows the most significant OS benefit but may be confounded with other factors. Keywords Clinicopathologic · Sampson and Scott criteria · Atypical endometriosis · Survival outcomes · Prognostic factors First author: Jie Deng. * Tianjin Yi 1 Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, People’s Republic of China 2 The Third People’s Hospital of Xindu District, Chengdu 610041, People’s Republic of China 3 West China School of Medicine, Sichuan University, Chengdu 610041, People’s Republic of China 4 Department of Pathology, West China Second University Hospital, Sichuan University, Chengdu 610041, People’s Republic of China Vol.:(0123456789) Archives of Gynecology and Obstetrics What does this study add to the clinical work? Applying the Sampson and Scott criteria to classify ovarian clear cell carcinoma patients by types of endometriosis involvement reveals distinct clinicopathologic characteristics and survival outcomes. Endometriosis presence, particularly in the coexisting subgroup, is an independent favorable factor for progression-free survival, while the arising subgroup shows improved 5-year overall survival, emphasizing the prognostic value of detailed endometriosis classification in patient management. Introduction Endometriosis is a chronic, estrogen-dependent, inflammatory disorder characterized by ectopic endometrial glands and stroma, affecting approximately 10% of reproductiveaged women [1]. Despite its benign nature, the chronic inflammation and immune dysregulation in endometriosis may increase the risk of infertility and cancer [2, 3]. Epidemiological evidence strongly links endometriosis with epithelial ovarian cancer (EOC), with particularly ovarian clear cell carcinoma (OCCC; OR = 3.05) and ovarian endometrioid carcinoma (OR = 2.04) [4]. OCCC, a histological subtype of EOC, is distinct in its clinical presentation, histopathology, and genetics [5]. Although relatively uncommon, OCCC accounts for approximately 5% to 12% of all EOC cases and up to 30% in Asian populations [6]. Although early stage OCCC patients have favorable outcomes, advanced or recurrent disease responds poorly to chemotherapy, resulting in worse prognoses compared to high-grade serous carcinoma [7, 8]. This highlights the urgent need for improved etiological understanding and prognostic markers. Endometriosis has been reported in 25–58% of OCCC cases [9–11]. Some studies suggest better prognoses in endometriosis-associated OCCC, potentially due to younger age and earlier disease stage at diagnosis [12–14]. However, other studies have failed to demonstrate significant survival differences between these groups [15, 16] or to establish endometriosis as an independent prognostic factor [17–19]. These inconsistencies leave the prognostic role of endometriosis in OCCC patients open to debate. Immunohistochemistry (IHC) plays a crucial role in accurately diagnosing OCCC and distinguishing it from other ovarian or metastatic carcinomas [20, 21]. OCCC typically demonstrates high expression of Paired box gene 8 (PAX-8) (approximately 95%), a reliable marker for ovarian origin, along with strong positivity for Hepatocyte nuclear factor-1 beta (HNF-1β) (92–100%) and Napsin A (83–100%), making these markers particularly useful for accurate diagnosis. Cytokeratin 7 (CK7) is consistently positive in nearly all cases (close to 100%), whereas Cytokeratin 20 (CK20) is usually negative, effectively differentiating OCCC from metastatic colorectal carcinoma, which typically expresses CK20. Wilms' tumor 1 (WT1) negativity (0–5% positivity) distinguishes OCCC from high-grade serous carcinoma, which strongly expresses WT1. Estrogen receptor (ER) and progesterone receptor (PR) are predominantly negative in OCCC, with ER positivity reported in approximately 10% of cases and PR positivity even less frequently (approximately 5%). The p53 protein usually exhibits wild-type expression patterns in OCCC; however, aberrant p53 staining occurs in approximately 10–24% of cases. In contrast, endometriosis tissues exhibit significantly elevated estrogen receptor beta (ER-β)—over 100-fold higher compared to normal endometrial tissue—and reduced PR expression [22]. These distinct hormonal receptor patterns in endometriosis likely contribute to its pathogenesis and resistance to treatment. Since Sampson's firs (...truncated)