Objective: To investigate the characteristics of human epidermal growth factor receptor 2 (HER2) protein expression and gene status in uterine serous carcinoma (USC) patients. Methods: A total of 36 formalin-fixed and paraffin-embedded USC tissue specimens obtained between 2021 and 2022 in Peking Union Medical College Hospital were collected. The expression of HER2 protein and the gene status were detected by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) respectively, and the results were interpreted according to the 2020 International Society of Gynecological Pathologists recommendations. Results: Among the 36 cases, 11, 8, 12 and 5 cases showed HER2 IHC scores of 0, 1+, 2+, and 3+, respectively. All IHC 3+cases were pure USC. Out of 25 samples with different level of HER2 expression (IHC 1+, IHC 2+and 3+), 16 (64.0%) tumors with heterogeneous stain, which mainly affects the diseases with IHC 2+ (10/12) and IHC 3+ (3/5) lesions. Ten pure USC cases (27.8%, 10/36), involving HER2 IHC 0, IHC 1+, IHC 2+and IHC 3+tumors, harbored HER2 gene amplification by FISH (1, 1, 3 and 5 cases, respectively). All amplified cases exhibited a HER2/CEP17 ratio≥2.0. In addition, the incidences of chromosome 17 (CEP17) polysomy and monosomy were 25.0% (9/36) and 19.4% (7/36), respectively. Conclusions: Most of USC tumors exhibit intratumoral heterogeneity in HER2 IHC stain. Both HER2 IHC positive (3+) and FISH positive occur exclusively in pure USC tumors. HER2 gene amplification can be observed in any HER2 IHC levels.

Our study aimed to preliminarily investigate the role of combined detection of serum CCL20 and Oncostatin M in the diagnosis of early-stage endometrial cancer (EC). A retrospective study was conducted on 109 patients with early-stage EC. Serum CCL20 and Oncostatin M levels were determined, and their correlations with sex hormone indicators (TTE and DHEAS) in EC patients were analyzed. Influencing factors for EC and the early diagnostic value of each indicator were analyzed. Serum CCL20 and Oncostatin M were high in EC patients and positively correlated with TTE and DHEAS. Elevated CCL20 and Oncostatin M were independent risk factors for EC. The diagnostic efficacy of serum CCL20 + Oncostatin M in combination was better than that of serum CCL20, Oncostatin M, CA125, and HE4 alone. The diagnostic test combining serum CCL20 and Oncostatin M in endometrioid carcinoma demonstrated an AUC of 0.855, with a sensitivity of 68.00% and a specificity of 92.86%, comparable to that in the whole early-stage endometrial carcinoma group (AUC = 0.867). Combined detection of serum CCL20 and Oncostatin M may offer a promising adjunctive approach for the diagnosis of early-stage EC, with their levels correlated to sex hormone and clinicopathological characteristics.

With the increasing public awareness of health, TikTok and Bilibili have become the domain source of short-video platforms for health-related information. This study aims to investigate the quality and reliability of short videos about endometrial cancer on two platforms. This cross-sectional study was conducted on TikTok and Bilibili to evaluate short videos related to endometrial cancer. The two platforms were searched using the term 'endometrial cancer' from 15:00 to 22:00 on 29 September 2025. The quality of related information was assessed by the Global Quality Score (GQS) and the modified DISCERN score (mDISCERN), and analyzed by descriptive statistics, inter-group comparison, and correlation analysis. 200 initial endometrial cancer-related videos were searched, and finally, 174 videos were included from TikTok and Bilibili. The GQS and mDISCERN scores of both platforms were low (median 2/5), and the median(Q1-Q3) duration of these videos was 80s (46.50-144.50), and the duration of Bilibili videos was longer (111 s to 63s, P < 0.001). The engagement with TikTok videos was relatively high (median likes: 1342 to 6, P < 0.001). Expert-uploaded videos were longer than those from other origins (median 109s) and of better quality (median mDISCERN 3/5, P < 0.001). The quality component was positively associated with the duration of short videos(r = 0.42-0.46). The five major dimensions of health demonstrated "fragmented content and insufficient depth": the highest coverage rate of symptoms was 36.2%, while the lowest coverage rate of prevention was 3.5%; the coverage rates of etiology, diagnosis, and therapy were all below 20%. Significant quality gaps exist in endometrial cancer videos. To enhance the structure and completeness of health information, professional participation should be strengthened in the future.

Background Predictive value of IGF2BP2 in combination with clinicopathological parameters for postoperative recurrence in endometrial cancer (EC): development and validation of a prognostic model. Methods This multicenter study retrospectively enrolled patients with endometrial cancer who underwent standard surgical treatment between January 2016 and January 2023. The cohort included 545 patients from the First Affiliated Hospital of Chongqing Medical University (training set) and 315 patients from two independent centers—Liangjiang Hospital of Chongqing Medical University and Women and Children’s Hospital of Chongqing Medical University (validation set). Univariate and multivariate Cox regression analyses were conducted to identify independent prognostic factors associated with recurrence-free survival (RFS), followed by the development of a nomogram-based prediction model. Model discrimination was evaluated using the area under the receiver operating characteristic curve (AUC), and calibration curves were used to assess the agreement between predicted and observed outcomes. Risk stratification was performed according to nomogram-derived scores, and the clinical applicability of the model was further validated through Kaplan-Meier survival analysis. Results Multivariate Cox regression analysis identified International Federation of Gynecology and Obstetrics(FIGO) stage (p=0.001), depth of myometrial invasion (p=0.004), histologic type (p=0.001), CA125 level (p=0.001), p53 status (p=0.013), lymphovascular space invasion (p=0.007), and IGF2BP2 expression (p&amp;lt;0.001) as independent prognostic factors for RFS in endometrial cancer patients. The integrated prediction model incorporating these factors demonstrated excellent performance in predicting 1-, 3-, and 5-year RFS, with significantly superior discriminative ability (AUC = 0.884) compared to single-parameter models. Conclusion The nomogram integrating IGF2BP2 with clinicopathological parameters demonstrates robust accuracy for predicting recurrence-free survival in endometrial cancer patients. This tool provides a quantitative risk stratification framework that could potentially contribute to prognostic assessment, though its clinical implementation awaits validation in prospective studies.

Endometrial cancer (EC) is a gynecologic malignancy with rising incidence globally, particularly in countries experiencing nutritional transitions. Diet quality may influence EC risk, yet evidence from non-Western populations remains limited. We conducted a hospital-based case-control study involving 136 histologically confirmed EC cases and 272 age- and BMI-matched controls in Tehran, Iran. Dietary intake was assessed using a validated 168-item food frequency questionnaire. Healthy Eating Index-2020 (HEI-2020) were computed to evaluate diet quality. Logistic regression was employed to estimate odds ratios (ORs) and 95% confidence intervals (CIs), controlling for reproductive factors, educational status, comorbidity, physical activity, and energy intake. Women in the highest tertile of HEI-2020 had 83% lower odds of EC compared to the lowest tertile (OR = 0.17; 95% CI: 0.09-0.30; P for trend < 0.001). The inverse association remained consistent across BMI categories and menopausal status. Greater intakes of vegetables, legumes, and plant-based proteins, along with reduced consumption of saturated fats, added sugars, and refined grains, were key dietary contributors. Greater adherence to the HEI-2020 was independently associated with reduced risk of EC among Iranian women. These findings emphasize the potential role of high-quality dietary patterns in cancer prevention and warrant confirmation in prospective studies across diverse populations.

DNA methylation analysis of self-collected samples has shown potential for primary endometrial cancer detection. Here, we aimed to explore DNA methylation testing as a non-invasive alternative for post-treatment surveillance. Endometrial cancer patients (n = 43) without recurrence collected pre- and post-treatment cervicovaginal self-samples and urine at home. Additionally, 17 patients with recurrence provided these samples at the time of recurrence. Healthy controls were used as reference. In total, 207 cervicovaginal self-samples and 203 urine samples were tested for nine markers (ADCYAP1, BHLHE22, CDH13, CDO1, GALR1, GHSR, HAND2, SST and ZIC1) using quantitative methylation-specific PCR. Diagnostic performance was assessed using previously established logistic regression models. In patients without recurrence, most marker levels decreased post-treatment compared to pre-treatment, in both sample types. DNA methylation positivity in cervicovaginal self-samples reduced from 90.7% pre-treatment to 19.5% post-treatment (p < .0001). In urine, a decrease from 80.5% to 20.9% was observed (p < .0001). In patients with recurrence, DNA methylation levels of CDH13, CDO1, GALR1, GHSR and HAND2 in cervicovaginal self-samples, and CDO1, GHSR and HAND2 in urine, were higher than in patients without recurrence. DNA methylation positivity was 62.5% in cervicovaginal self-samples and 58.8% in urine among patients with any recurrence, and 100% in cervicovaginal self-samples and 90.0% in urine of patients with a local recurrence specifically. These findings support methylation-based testing as a promising post-treatment surveillance method for endometrial cancer patients. This non-invasive approach could reduce the follow-up burden on patients and healthcare, alleviating challenges related to resource constraints while improving patient comfort.

Background and Objectives: Gynecological cancers frequently require radiation therapy (RT) in primary, adjuvant, or salvage settings. However, photon-based RT is associated with non-negligible toxicity, and treatment of pelvic recurrences after prior irradiation remains challenging. Proton beam therapy (PBT), due to its favorable dose distribution and reduced exposure of organs at risk (OARs), has emerged as a potential alternative, particularly in re-irradiation scenarios. Despite its expanding use in other malignancies, evidence supporting PBT in gynecologic cancers remains limited. This systematic review aims to investigate the use of PBT in gynecological cancers and its associated complications. Materials and Methods: This systematic review was conducted according to PRISMA guidelines and registered in PROSPERO. A comprehensive search (2000–2025) identified studies investigating PBT in gynecologic cancers. Eligible designs included randomized trials and prospective and retrospective series. Reported adverse events were categorized as GI, GU, or other, and only grade ≥3 CT-CAE complications were considered. Results: Of 580 records screened, 9 studies comprising 232 patients met inclusion criteria. Most patients were treated for endometrial (n = 147) or cervical (n = 75) cancer; 90 received chemotherapy. Overall, severe toxicity occurred in 15.2% of patients. GI complications ranged from 0–14% and GU from 0–33%. Complication rates were lowest in adjuvant or de novo treatment series (0–10%), whereas re-irradiation cohorts showed higher rates (up to 33% GU). Comparative studies suggested a possible advantage of PBT over IMRT, particularly for GI toxicity, though data remain limited. Conclusions: Severe GI and GU toxicity after PBT in gynecologic cancers appears infrequent, particularly in primary and adjuvant settings, though re-irradiation remains challenging. Current evidence is restricted to small and heterogeneous studies. Ongoing phase II trials will provide prospective data to clarify feasibility, toxicity, and long-term outcomes. Until then, PBT in gynecologic oncology should be regarded as investigational.

Analysis of DNA mismatch repair and microsatellite instability in molecular typing of endometrial carcinoma.

Endometrial carcinoma (EC) is the most common gynecologic malignancy. NOTCH-1, a transmembrane receptor involved in cell fate regulation, may act as an oncogene or tumor suppressor depending on context. Although NOTCH signaling is implicated in many cancers, its role in EC remains unclear. This study aimed to investigate the relationship between NOTCH-1 protein expression and a wide range of clinicopathological and immunohistochemical parameters, as well as its prognostic significance in EC. A total of 259 patients with EC were retrospectively analyzed. Immunohistochemical staining for NOTCH-1 was performed on tumor tissue sections. Associations between NOTCH-1 expression and clinicopathological features (age, tumor grade, FIGO stage, and invasion patterns) and immunohistochemical markers (ER, PR, p53, Ki-67, PTEN, CerbB2, and MSI) were evaluated. NOTCH-1 expression was positive in 37 (14.3%) cases. No significant association was found between NOTCH-1 expression and age, tumor grade, FIGO stage, or invasion-related parameters. However, PR positivity (P=0.01) and high p53 expression (P=0.01) were significantly more frequent in the NOTCH-1 positive group. There were no significant correlations with ER, Ki-67, PTEN, MSI, or CerbB2. NOTCH-1 expression was not associated with key clinicopathological or survival parameters in this cohort. While some molecular correlations were observed, NOTCH-1 does not appear to have strong prognostic utility in EC. Further research integrating molecular classification and long-term follow-up is needed to clarify its potential role in tumor biology.

Mismatch repair gene status by immunohistochemistry in endometrial hyperplasia, endometrial intraepithelial neoplasia and endometrial carcinoma

The Geriatric-8 (G8) is used for the functional status of older adult patients with cancer. However, its role in treatment decision-making for gynecological malignancies has not been established. We retrospectively analyzed the data of 180 women aged ≥75years with gynecological malignancies who underwent initial treatment at our institution between January 2019 and December 2023. Pre-treatment G8 scores were assessed and patients were categorized as fit (G8>14) or frail (G8≤14). Associations between the G8 score and patient background, disease characteristics, treatment options, and treatment tolerability were examined. Of the 180 women, 53 (29.4%) were classified as fit and 127 (70.6%) as frail. Frail patients required long-term care (P=.008) and used anticoagulants more frequently than fit patients (P=.019). Median G8 scores were highest in endometrial cancer (14) and lowest in vulvar cancer (10). Best supportive care (8) and neoadjuvant chemotherapy (10) had lower G8 scores than surgery and concurrent chemoradiotherapy (14) (P<.001). Postoperative complications occurred in 10/96 surgical cases; these cases had lower scores than those without complications (12 vs. 14, P=.044). During chemotherapy, median scores were lower in women with ≥ grade 3 (12 vs. 14, P=.008) and grade≥4 adverse events (10 vs. 14, P=.002). The G8 score is associated with patient background, cancer type, and treatment options, and is associated with treatment tolerability in women aged ≥75years with gynecological malignancies.

Deep learning is expected to aid pathologists in tasks such as tumour segmentation. We developed a general tumour segmentation model for histopathological images and examined its performance in different cancer types. The model was developed using over 20,000 whole-slide images from over 4000 patients with colorectal, endometrial, lung, or prostate carcinoma. Performance was validated in pre-planned analyses on external cohorts with over 3000 patients across six cancer types. Exploratory analyses included over 1500 additional patients from The Cancer Genome Atlas. Average Dice coefficient was over 80% in all validation cohorts with en bloc resection specimens and in The Cancer Genome Atlas cohorts. No performance loss was observed when comparing the general model with single-cancer models specialised in cancer types from the development set. In conclusion, extensive and rigorous evaluations demonstrate that generic tumour segmentation by a single model is possible across cancer types, patient populations, sample preparations and slide scanners.

Background: Granulosa cell tumors (GCTs) are rare ovarian sex cord–stromal neoplasms characterized by estrogen secretion, which can result in prolonged endometrial stimulation. This hormonal activity increases the risk of synchronous endometrial and uterine pathology, particularly in women presenting with abnormal uterine bleeding. Failure to recognize concurrent uterine disease may lead to diagnostic delay or suboptimal surgical management. Case Presentation: This descriptive case series includes five women aged 44–62 years who presented with abnormal uterine bleeding, postmenopausal bleeding, or abdominal pain. Pelvic imaging in all patients revealed adnexal masses suspicious for ovarian pathology. All patients underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy. Histopathological examination confirmed adult-type granulosa cell tumors in all cases, with coexisting uterine and endometrial pathologies including endometrioid adenocarcinoma, disordered proliferative endometrium, adenomyosis, leiomyoma, and chronic cervicitis. Results: Synchronous uterine or endometrial pathology was identified in all five patients. One patient had FIGO stage IB endometrioid endometrial carcinoma, while the remaining cases demonstrated benign but clinically significant uterine conditions. Postoperative recovery was uneventful in all patients. The findings underscore the diagnostic value of comprehensive uterine evaluation in patients with suspected ovarian granulosa cell tumors. Conclusion: Granulosa cell tumors may coexist with significant uterine and endometrial pathology due to estrogen excess. This case series highlights the importance of routine endometrial assessment in women with suspected GCTs, particularly those presenting with abnormal uterine bleeding, to ensure accurate diagnosis and optimal surgical planning. Larger prospective studies are required to better define the prevalence and clinical implications of synchronous pathology. Keywords: Abnormal Uterine Bleeding, Endometrial Pathology, Estrogen-Secreting Ovarian Tumor, Granulosa Cell Tumor, Synchronous Gynecologic Disease.

Application progress of tRNA modification in gynecological tumors: A review.

Background Oxidative stress plays a crucial role in the development and treatment response of endometrial cancer, yet the antioxidant defense mechanisms in different tumor subtypes remain unclear. Methods We investigated the cellular response to oxidative (menadione) and genotoxic (doxorubicin) stress in two TP53-mutated endometrial cancer cell lines, AN3CA and KLE. Cell viability, reactive oxygen species (ROS) levels, and the expression of antioxidant-related genes (SESN2, SESN3, SOD1) were assessed using qPCR and In-Cell Western assays. Results AN3CA cells showed greater sensitivity to doxorubicin, marked by increased ROS and reduced viability, while KLE cells were more susceptible to menadione-induced toxicity. Protein expression analysis revealed a biphasic response: low doses of doxorubicin transiently increased SESN and SOD1 expression, whereas higher doses suppressed them. Gene expression at the mRNA level did not always correlate with protein levels, suggesting possible post-transcriptional regulation. Conclusion Our findings demonstrate cell line - specific redox responses and identify SESN2, SESN3, and SOD1 as key players in the antioxidant defense network. These genes may serve as potential therapeutic targets in aggressive, hormone-independent endometrial cancers.

The development of endometrial cancer is a gradual malignant transformation process driven by multiple factors, and the immune microenvironment is closely related to clinical outcomes and immunotherapy responses. Under physiological conditions, the immune microenvironment of the normal endometrium undergoes periodic reshaping under the regulation of estrogen and progesterone, maintaining the balance between immune defense and reproductive capacity. However, continuous exposure to risk factors, such as non-antagonistic estrogen, may trigger endometrial intraepithelial neoplasia. During this period, the immune microenvironment becomes dysregulated, supporting malignant progression. For example, estrogen-stimulated interactions between endothelial cells and macrophages, elevated neutrophil/lymphocyte ratios, and the accumulation of regulatory T cells all combine to cause dysregulation of immune microenvironment. The abnormal immune microenvironment that occurs in the precancerous lesion stage interacts with systemic and genetic carcinogenic factors, ultimately shaping the unique immune microenvironment of each molecular subtype of endometrial cancer. POLE-mutated and MSI-H subtype endometrial cancer are immune-infiltrated tumors, whereas the copy-number high subtype is immune-suppressive tumor and the copy-number low subtype is immune-desert tumor. However, still little is known about the immune dysregulation that occurs during the precancerous stage and its impact on subsequent malignant progression. This review systematically describes the changes in the immune microenvironment during the process from normal endometrium to endometrial cancer, emphasizing that endometrial intraepithelial neoplasia is a key stage of immune imbalance, thus paving the way for early immune intervention and precise immunotherapy.

Gynecologic cancers remain a leading cause of morbidity and mortality in women, and recent years have marked an inflection point through the consolidation of immunotherapy, the maturation of antibody-drug conjugates, and broader biomarker implementation. This narrative review synthesizes key clinical and translational advances across ovarian, endometrial, and cervical cancers in 2025, emphasizing implications for treatment selection and sequencing. In advanced ovarian cancer, TRUST re-examined surgical timing, supporting primary cytoreduction in selected resectable patients, whereas ICON8B suggested that weekly paclitaxel with carboplatin and bevacizumab may improve outcomes in high-risk disease. Platinum-resistant ovarian cancer saw the most disruptive progress: mirvetuximab soravtansine validated folate receptor-α as a therapeutic target, with overall survival benefit in high-expressing tumors; trastuzumab deruxtecan expanded actionable HER2 disease, with greatest activity in tumors rated 3+ by immunohistochemistry; and combination strategies, including relacorilant plus nab-paclitaxel and pembrolizumab plus weekly paclitaxel ± bevacizumab, delivered clinically meaningful survival signals, underscoring the need for harmonized biomarker strategies and proactive toxicity mitigation. In endometrial cancer, the Cancer Genome Atlas-based molecular classification increasingly informs risk stratification and adjuvant tailoring; long-term PORTEC-3 data refine escalation for p53-abnormal disease and de-escalation considerations for POLE-mutant tumors. In advanced disease, first-line chemo-immunotherapy has matured, with overall survival updates in mismatch repair-deficient tumors and a consistent progression-free survival benefit across diverse mismatch repair-proficient sub-groups, whereas adjuvant immunotherapy remains in evolution after KEYNOTE-B21. In cervical cancer, pembrolizumab added to definitive chemoradiotherapy set a new benchmark in locally advanced disease, and ultra-sensitive circulating tumor DNA analyses emerged as a powerful prognostic tool to enable post-treatment risk-adapted strategies. Collectively, the 2025 data set reinforces a "right therapy, right patient, right time" paradigm and prioritizes confirmatory antibody-drug conjugate trials, resistance biology, and dynamic biomarkers to translate gains into durable, equitable benefit.

Trends, predictors, and safety of ovarian preservation in premenopausal women with high-grade endometrioid and non-endometrioid endometrial cancers.

While the role minimally invasive surgery (MIS) is established for primary endometrial carcinoma (EC), its feasibility in recurrent cases remains underexplored. To systematically review the literature about MIS for EC recurrence. A systematic literature search was conducted across six electronic databases, targeting studies published until October 31, 2024. Inclusion criteria encompassed all peer-reviewed studies reporting MIS for recurrent EC. Data extraction focused on surgical outcomes and survival metrics, following PRISMA guidelines. Out of 9652 results, 15 studies with 17 cases of patients with EC recurrence met the inclusion criteria. All patients underwent successful MIS, with no intraoperative complications reported. Complete resection (when reported) was achieved in 100% of cases, and adjuvant treatment was administered in 64.7% of patients. The mean follow-up duration was 23.6 months, with a disease-free survival rate of 63.6%. Risk of bias assessment indicated a predominance of low to medium risk of bias within studies. MIS might be feasible and safe in cases of abdominal recurrence of EC when the number of recurrence localizations is less than three. MIS might be a management option independently from EC histology, grade and stage (except for stage IV), previous adjuvant therapy and group of risk. The endoscopic approach could be both laparoscopic and robotic, without any apparent difference in terms of feasibility, safety and survival outcomes. However, data on this topic are limited and our findings need to be confirmed by additional studies.

Given the increasing incidence of endometrial cancer (EC) and the lack of improvement in survival rates, it is imperative to explore possible prevention methods. Studies on aspirin's effect on EC risk have been controversial; research on ibuprofen remains limited. We therefore aimed to investigate the relationship between aspirin and ibuprofen use and risk of EC through a cohort study. This analysis was based on the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, which recruited participants aged 55-74 years from 1993 to 2001, with follow-up for cancer incidence continuing until December 31, 2009. A total of 42,394 women were enrolled in this analysis, and 678 cases of EC were diagnosed during a median follow-up period of 12.0 years. Compared with an intake of <4 pills per month, the use of ibuprofen ≥30 pills per month significantly reduced EC risk (fully-adjusted hazard ratio [HR], 0.75; 95% confidence interval [CI]: 0.58-0.98), particularly in participants with a history of cardiovascular disease (fully-adjusted HR, 0.57; 95% CI: 0.37-0.87). No evidence was found for an association between aspirin and EC occurrence in the general population (fully-adjusted HR, 0.98; 95% CI: 0.81-1.19), nor in specific subgroups. In conclusion, frequent ibuprofen use, unlike aspirin, was linked to reduced EC risk. This protective effect of ibuprofen was enhanced in women with a history of cardiovascular disease. Additional well-designed, prospective research is needed to validate these findings and explore the underlying mechanisms.