To assess the necessity of restaging surgery for patients with suspected International Federation of Gynecology and Obstetrics (FIGO) stage I-II epithelial ovarian cancer (EOC) following incomplete surgical staging. This multicenter retrospective study evaluated patients with early-stage EOC referred for restaging. These patients were diagnosed with suspected FIGO stage I-II EOC between January 2007 and November 2022 after incomplete surgical staging, and no residual region was confirmed by radiological evaluation. Progression-free survival (PFS) and overall survival (OS) were examined. Among the 173 patients included in the study, 56 were assigned to the no restaging surgery group, and 117 to the restaging surgery group. After restaging, 23 were upstaged to other main stage. However, PFS and OS were not significantly different between the groups, also, dividing the groups into 4 groups who underwent chemotherapy and those who did not also did not show significant differences. In multivariate analysis, histologic grade independently influenced PFS outcomes. While restaging surgery resulted in upstaging in some patients, it was not associated with significant differences in PFS or OS in this retrospective analysis. However, the omission of any additional treatment warrants careful consideration and further discussion. Nevertheless, the observation that patients who did not undergo restaging surgery but received adjuvant chemotherapy did not show significantly different prognoses highlights the need for further research to establish appropriate treatment strategies tailored to diverse patient contexts.

Intraperitoneal infusion of stem cell-derived natural killer cells in recurrent epithelial ovarian cancer patients: Results of the phase 1 INTRO-01 trial.

This study aimed to assess the impact of comprehensive staging on survival outcomes in this population. Patients who underwent surgery for epithelial ovarian cancer in one of the 14 Francogyn cancer centers between 2000 and 2020 were included in the study. The primary analysis evaluated the impact of lymphadenectomy on overall survival and recurrence-free survival. Lymph node count was analyzed as a continuous variable, and its association with survival, considered as a continuous outcome was assessed using linear regression (secondary analysis). Survival was compared using the log-rank test, and multivariate analysis was performed using a Cox model. A total of 467 patients with presumed early-stage epithelial ovarian cancer were included, of which 198 underwent complete lymphadenectomy and 266 did not. No significant association was found between lymph node staging and survival in the primary analysis, possibly due to limited statistical power and a selection bias, as patients without lymphadenectomy had more favorable disease profiles (p=0.600 and p=0.700, respectively). Complete lymphadenectomy was associated with a significantly higher risk of complications (34.5% vs. 14%, p<0.001). In secondary analysis, the number of para-aortic lymph nodes harvested was identified as an independent predictor of both overall survival and recurrence-free survival (p=0.007 and p=0.002, respectively). Histological characteristics and adjuvant chemotherapy also showed a significant correlation with improved survival outcomes. Extensive para-aortic lymphadenectomy in early-stage epithelial ovarian cancer is associated with better overall and recurrence-free survival but comes with an increased risk of complications.

Targeting BRD4 in cancer therapy: From inhibitors and degraders to novel combination strategies and resistance mechanisms.

Pathogenic germline variants among patients with ovarian cancer by self-reported ancestry: A commercial laboratory collaborative research registry study.

First experience with intraperitoneal 224Ra-labeled microparticles after cytoreductive surgery in patients with peritoneal recurrence of platinum-sensitive epithelial ovarian cancer.

Cisplatin remains a standard first-line therapy for epithelial ovarian cancer; however, chemoresistance leads to poor prognosis and high recurrence. Analysis of The Cancer Genome Atlas confirmed improved overall survival in cisplatin-sensitive tumors, underscoring the need for strategies to overcome resistance in clinical settings. Integrative bioinformatics of cisplatin-treated ovarian cancer datasets from the Gene Expression Omnibus (n=255) identified six molecular drivers of resistance: Kaiso (ZBTB33), pregnane X receptor (PXR), NF-κB, HER2 (ERBB2), P-glycoprotein (P-gp/ABCB1), and HIF1A. These targets were validated in ovarian tumor specimens via immunohistochemistry, confirming elevated expression in chemo-resistant disease. Additionally, the quantitative real-time PCR analysis confirms the transcriptional upregulation of the six resistance-associated genes in cisplatin-resistant SKOV3 and OVCAR-5 ovarian cancer cells, consistent with the immunohistochemistry findings. The average fold change in mRNA transcripts ranged from 2.4 for P-glycoprotein to 5 for both NF-kB and Kaiso. Although less well studied in ovarian cancer, Kaiso is known to regulate EMT and tumor invasion in other solid tumors. Functional studies using SKOV3 and OVCAR-5 cell lines demonstrated that knockdown of Kaiso via RNA interference significantly increased cisplatin-induced cell death, indicating a direct role in therapeutic resistance. Furthermore, we investigated the synergistic effects of combining stearidonic acid (SDA), a plant-based omega-3 fatty acid known to inhibit NF-κB, with cisplatin on cell death in SKOV3 and OVCAR-5 cell lines, and compared the results with those of each compound used individually. Interestingly, co-treatment with stearidonic acid (SDA) synergistically enhanced the cytotoxicity of cisplatin at a lower dose in both cell models. These findings reveal a clinically relevant resistance signature and highlight the therapeutic potential of combinatorial strategies that target both transcriptional regulators (e.g., Kaiso) and inflammatory signaling (e.g., NF-κB). Dual targeting of these pathways may resensitize tumors to cisplatin and improve outcomes for patients with advanced ovarian cancer.

Introduction: Undifferentiated and dedifferentiated ovarian carcinomas are rare, aggressive neoplasms. While the dedifferentiated component may exhibit neuroendocrine differentiation, this is typically limited to less than 10% of the tumor. Case Report: We report a unique case of a 73-year-old woman with a high-grade ovarian adenocarcinoma containing a morphologically distinct, diffusely neuroendocrine-rich component. Histologically, the tumor demonstrated two distinct patterns: a well-differentiated yet cytologically high-grade adenocarcinoma adjacent to sheets of monotonous, largely dyscohesive high-grade tumor cells with diffuse neuroendocrine marker expression. The dual morphology raised consideration of a mixed adenocarcinoma–neuroendocrine carcinoma as part of the diagnostic differential. Conclusion: This case describes an uncommon ovarian carcinoma that shows more than 10% diffuse neuroendocrine differentiation which is not typically encountered in dedifferentiated ovarian carcinomas. The combination of high-grade adenocarcinoma with a neuroendocrine-rich component suggests a mixed adenocarcinoma–neuroendocrine carcinoma, a pattern that, to our knowledge, has not been previously documented in the ovary. These observations emphasize the importance of maintaining a broad differential diagnosis when evaluating ovarian carcinomas with prominent neuroendocrine features.

Relevance: Epithelial ovarian cancer remains one of the leading causes of mortality among gynecological malignancies, particularly in stages III-IV, when peritoneal spread is detected in the majority of patients. Despite advances in surgery and systemic chemotherapy, more than 70% of patients develop recurrence. In this context, hyperthermic intraperitoneal chemotherapy (HIPEC) combined with cytoreductive surgery is being actively investigated. The study aimed to summarize and critically analyze the current evidence on the efficacy, safety, and indications for HIPEC in advanced and recurrent ovarian cancer to determine the HIPEC role in clinical practice. Methods: Publications from the last 10-15 years (PubMed, Scopus, clinicaltrials.gov) were reviewed, including randomized controlled trials, meta-analyses, as well as prospective and retrospective series. Results: The strongest evidence comes from studies demonstrating that the use of HIPEC during interval cytoreduction improves progression-free and overall survival in patients with advanced ovarian cancer. Several large trials have also reported improved overall survival in patients with a first platinum-sensitive recurrence; however, other randomized trials have failed to confirm these findings, highlighting the need for further clarification of patient selection criteria. Conclusion: HIPEC appears to be a promising addition to standard therapy, especially in patients with stage III epithelial ovarian cancer and those with platinum-sensitive recurrences. Limiting factors include high toxicity, the lack of standardized protocols, and substantial costs.

To develop a nomogram based on CT and clinical features to predict R0 resection in patients with stage IIB-IV epithelial ovarian cancer (EOC). 209 patients with stage IIB-IV EOC from three independent medical institutions were stratified into training cohort (from institutions 1 and 2, n = 144) and independent validation cohort (from institution 3, n = 65). Univariate and multivariate logistic analyses of CT and clinical features obtained within two weeks before debulking surgery were used to determine the independent predictors of R0 resection in the training cohort. Nomogram was developed based on the predictors. Receiver operating characteristic (ROC) curves and calibration curves were performed to evaluate the predictive performance of the nomogram. R0 resection was achieved in 66.00 and 61.50% patients in the training and validation cohorts, respectively. In the training cohort, overall peritoneal cancer index based on CT (CT-PCI) (OR 1.245, P < 0.001), serum human epididymis protein4 (HE4) level (OR 1.003, P = 0.012), and neutrophil-to-lymphocyte ratio (NLR) (OR 1.272, P = 0.031) were independent predictors of R0 resection in patients with stage IIB-IV EOC. Nomogram based on them achieved areas under the ROC curves of 0.908 (95% CI 0.848-0.950) and 0.779 (95% CI 0.659-0.873) in the training and independent validation cohort, respectively. The calibration curves showed good agreement between the nomogram predictions and the actual observations in both cohorts. The nomogram based on overall CT-PCI, serum HE4 level, and NLR could be reliable in predicting R0 resection in EOC patients with stage IIB-IV.

FOXL2 + cancer-associated fibroblasts enhances epithelial ovarian cancer development via TGFβ/Smad signaling.

Introduction: Ovarian cancer (OC) ranks as the fifth most common gynecologic malignancy among women worldwide. Objective: The present study evaluates the diagnostic potential of hematological biomarkers for the early detection and differential diagnosis of OC. Methods: A bioinformatic analysis was performed to compare immune cell profiles in blood and tissue samples from patients with OC using data from The Cancer Genome Atlas and Gene Expression Omnibus databases. Subsequently, a retrospective clinical study was conducted at Yichang Central People&amp;rsquo;s Hospital between January 2015 and January 2021, including three cohorts: (i) Patients with benign ovarian tumors (n = 70), (ii) Patients with OC (n = 70), and (iii) Healthy controls (n = 60). A comprehensive analysis of routine blood parameters and the tumor marker cancer antigen 125 (CA125) was performed. Results: The findings revealed that peripheral blood immune markers exhibited superior diagnostic utility compared with tissue-based indicators. The combination of CA125 with erythrocyte sedimentation rate (ESR) and neutrophil-to-lymphocyte ratio showed high accuracy in differentiating benign ovarian tumors from OC (area under the curve [AUC]: 0.87). Furthermore, a panel combining CA125 and platelet-to-neutrophil ratio showed enhanced diagnostic performance in distinguishing early-stage from advanced epithelial OC (sensitivity: 81.3%; specificity: 96.6%). Notably, the triad of CA125, ESR, and white blood cell count demonstrated strong screening performance for detecting epithelial OC (AUC: 0.941; p&lt;0.001). Conclusion: These results suggest that integrating CA125 with routine hematological parameters significantly enhances the diagnostic accuracy and early detection of epithelial OC compared to CA125 alone, providing a practical and cost-effective screening strategy for clinical implementation.

IntroductionEpithelial ovarian cancer (EOC) has a dismal prognosis, and recent therapeutic advancements have been limited. The aim of our study was to clarify the role and mechanism of cetrorelix in EOC apoptosis and to evaluate the clinical relevance of GnRHR, AKT, and FOXO1 in EOC patients.MethodsApoptosis was assessed using flow cytometry, Hoechst staining, and Western blotting. FOXO1, p-AKT and GnRHR knockdown via siRNA was performed to reverse cetrorelix-induced apoptosis. Mechanistic insights were explored using apoptosis gene PCR arrays, qRT–PCR, and Western blotting. In vivo efficacy was tested in a xenograft mouse model. Immunohistochemistry (IHC) was used to assess GnRHR, AKT,p-AKT and FOXO1 expression in EOC tissues, and survival analysis was performed using Kaplan–Meier and Cox regression analyses.ResultsCetrorelix facilitated EOC apoptosis both in vitro and in a xenograft model. The results of apoptosis PCR arrays linked cetrorelix treatment to the upregulation of the TNF/TNF receptor superfamily (a FOXO1-dependent mechanism). Mechanistically, cetrorelix upregulated FOXO1 expression, and FOXO1 knockdown attenuated cetrorelix-induced apoptosis. Furthermore, cetrorelix-mediated suppression of p-AKT expression and subsequent FOXO1 activation occurred via the PI3K/AKT signaling axis. This mechanism was substantiated by the findings that the PI3K inhibitor LY294002 mimicked cetrorelix’s effects without producing an additive apoptotic response, and that GnRHR knockdown abrogated cetrorelix-induced apoptosis, confirming receptor specificity. Experiments in xenograft models recapitulated the PI3K/AKT/FOXO1 cascade modulation observed in vitro. However, the in vivo activation status of FOXO1 was not quantitatively assessed or localized within the xenograft tissues. Clinically, FOXO1/GnRHR positivity and AKT negativity were correlated with early-stage disease (FIGO I-II, p < 0.05), no metastasis (p < 0.05), and improved survival (log-rank p < 0.05). Multivariate analysis revealed GnRHR positivity, AKT negativity, low-grade pathological type and early FIGO stage as independent risk factors for improved overall survival.ConclusionThese findings suggest that cetrorelix may induce EOC apoptosis via the PI3K/AKT–FOXO1 pathway, which provides mechanistic support for the therapeutic potential of GnRH antagonists in EOC management. Moreover, the identified critical regulatory pathways are prospective therapeutic targets for EOC management.

Abstract Background and Objective Epithelial ovarian cancer is typically diagnosed later in life, at a median age of 63 years. Early-onset ovarian cancer (&amp;lt;50 years of age) comprises roughly a fifth of all new diagnoses. Few risk factors are established for ovarian cancer, and there may be differences according to age at onset. Given this, we aimed to describe and explore whether associations with multiple lifestyle and reproductive risk factors differed between early and late-onset invasive ovarian cancer. Methods This study utilized data from a population-based case-control study conducted in Montreal, Canada from 2011 to 2016, including 364 incident cases of invasive epithelial ovarian cancer and 908 population controls frequency-matched to cases by age. Information on various lifestyle and reproductive factors were collected during in-person interviews. Unconditional logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) between each factor and risk. To assess potential differences according to age at onset (early vs. late), models included an interaction term between the factor of interest and a binary age at diagnosis variable (&amp;lt;50 vs. 50+ years). The specific lifestyle and reproductive factors examined in this analysis included alcohol consumption, caffeine intake, vitamin D, residential air pollution, childhood body shape, adult body mass index, shift work, sleep, regular analgesic use, smoking, age at menarche, parity, age at first/last birth, oral contraceptive duration, and lifetime number of ovulatory cycles. Results Overall, 19.0% of all cases were early-onset (n=69). The distribution by histotype varied greatly, with high-grade serous comprising 43.5% of early-onset cancers vs. 72.2% of later-onset. The second most frequent histotype among early-onset cases was mucinous (14.5%). In addition, stage at diagnosis differed with 40.6% and 20.3% of early- and later-onset cases, respectively, diagnosed at stage 1 and 45.0% and 65.1% at stage 3/4. Among the lifestyle factors examined in relation to risk, lifetime intake of alcohol and caffeine as well as cumulative smoking exposure tended to be associated with an increased risk of early-onset ovarian cancer but showed a null association with later-onset cancer. Conversely, lifetime vitamin D exposure was associated with a reduced risk only for later-onset disease. Confidence intervals were wide for all results, and with other lifestyle factors, differences by age at onset were difficult to discern. For reproductive factors, observed associations were similar for early- and later-onset ovarian cancer, except for lifetime number of ovulatory cycles for which a positive association was stronger for early-onset cancers. Conclusion We observed some suggestion that certain lifestyle and reproductive factors may differently influence the risk of invasive epithelial ovarian cancer depending on age at onset. These differences may reflect differences in histotype distributions and pathogenesis. Further research is needed to better understand differences. Citation Format: Anita Koushik, Marie-Hélène Mayrand, Ari N. Meguerditchian, Claudia Waddingham. Lifestyle and reproductive factors and early-onset invasive epithelial ovarian cancer risk [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: The Rise in Early-Onset Cancers—Knowledge Gaps and Research Opportunities; 2025 Dec 10-13; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(23_Suppl):Abstract nr B019.

Machine-learning survival models for predicting time to recurrence in epithelial ovarian cancer.

This study aimed to investigate the role of FAM172A in epithelial ovarian cancer (EOC), a highly lethal gynecological malignancy often diagnosed at late stages with limited treatment options. FAM172A expression was evaluated in EOC and normal ovarian tissues using western blotting and immunohistochemistry, and its association with patient prognosis, treatment response, and CA125 levels was assessed by multivariate regression analysis. Functional assays were performed to examine the effects of FAM172A on EOC cell proliferation, migration, and invasion. In vivo models were used to evaluate the influence of FAM172A on tumor growth, metastasis, and chemosensitivity. The underlying mechanism was explored by modulating the PI3K-Akt pathway with pharmacological inhibitors and activators. FAM172A was significantly upregulated in EOC tissues, and its elevated expression correlated with poor prognosis, chemotherapy resistance, and increased CA125 levels. Multivariate analysis identified FAM172A expression, platinum sensitivity, and CA125 as independent prognostic factors. In vitro, FAM172A promoted malignant behavior and conferred resistance to cisplatin. In vivo, knockdown of FAM172A suppressed tumor progression and enhanced the efficacy of cisplatin. Mechanistically, FAM172A exerted its effects through regulation of the PI3K-Akt pathway, and modulation of PI3K signaling rescued FAM172A-induced phenotypic changes. These findings highlight FAM172A as a critical promoter of EOC progression, associated with aggressive tumor characteristics and treatment failure. By activating the PI3K-Akt pathway, FAM172A represents a promising therapeutic target for EOC, potentially offering new strategies to improve patient outcomes, particularly in overcoming chemoresistance.

Frailty and body composition as predictors of postoperative outcomes in patients with epithelial ovarian cancer undergoing neoadjuvant chemotherapy.

The cyclin-dependent kinase inhibitor p27 facilitates chemosensitivity by promoting ferroptosis in epithelial ovarian cancer.

The umbrella term "epithelial ovarian cancer" encompasses 5 histologic sub-types with distinct molecular profiles and varying sensitivities to chemotherapy. Historical trials investigating adjuvant management of early-stage disease have not accounted for this heterogeneity. This review examines the evidence guiding the management of stage I and II epithelial ovarian cancer according to histologic sub-type and discusses its application in contemporary modern setting. Areas of interest for future research are highlighted, with an emphasis on the need for more personalized adjuvant therapy using predictive biomarkers and targeted treatments.

This study aims to evaluate the expression of BRCA1 and MMR proteins using immunohistochemistry (IHC) in epithelial ovarian cancers and to explore their clinicopathological correlations. IHC was performed and interpreted for BRCA1, MLH1, MSH2, MSH6, and PMS2. The results were then compared with clinical and pathological variables. Over a period of 19 months, 508 specimens containing ovarian tissue were received, either as part of a hysterectomy or as isolated samples for various indications. Among these, 24.01% (122/508) showed invasive epithelial ovarian cancer. Of these, 49 resection specimens had sufficient tumor tissue for detailed immunohistochemistry (IHC) analysis and were included in the study. Among the evaluated cases, 51% (25/49) of invasive epithelial ovarian cancers exhibited deficient mismatch repair (dMMR). No significant correlation was observed between dMMR and pMMR with respect to grade, cellularity, and high-grade features. Patients with dMMR showed better survival, which may be due to improved response to chemotherapy in these cases. Total loss of BRCA1 was seen in 36.7% (18/49) of cases. BRCA1 loss was associated with poor predictive factors but had better prognosis. Loss of BRCA1 was associated with aggressive tumors but had better response to chemotherapy. Both MMR and BRCA1 were independent variables. The overall survival of our patient population with epithelial ovarian cancer was 86.8%. A significant number of patients displayed dMMR and BRCA1 loss by IHC. These patients may benefit from targeted therapy, and IHC may serve as an acceptable technique for each evaluation.