Search Results (400)

Background/Objectives: Prognostic assessment in endometrial cancer (EC) is based on clinical and pathological features such as histological type, FIGO stage, tumor grade, LVSI, P53 status, and hormone receptor expression. Recent molecular research has distinguished four EC subtypes, with MMR status (pMMR vs. dMMR) providing clinically relevant stratification due to its predictive value for immunotherapy. The present study aims to compare dMMR and pMMR tumors in terms of the prevalence of adverse histopathological prognostic factors. Methods: This retrospective study included 179 patients with endometrioid endometrial carcinoma (EEC) treated at the authors’ institution (1 January 2023–31 August 2025). Patients were classified by MMR status (pMMR vs. dMMR) based on immunohistochemistry, and clinicopathological variables, including FIGO stage, myometrial invasion depth, tumor grade, LVSI, ER/PR expression, and P53 status, were analyzed. Normality was assessed using the Shapiro–Wilk test. Categorical variables were tested with chi-square or Fisher’s exact tests, reporting odds ratios with 95% CI, while continuous variables were compared using the Mann–Whitney test and presented as median (IQR) with the Hodges–Lehmann difference and 95% CI. Multivariable logistic regression with Wald tests was performed. Results: dMMR tumors accounted for 29.05% of all cases. Patients in the dMMR group were significantly more likely to present with FIGO stage III/IV disease (p = 0.036) and to exhibit LVSI (p = 0.008). No differences were observed between the groups with respect to tumor grade, estrogen receptor positivity, progesterone receptor positivity, or the prevalence of deep myometrial invasion. The most frequent pattern of protein loss in the dMMR population was concurrent loss of MLH1 and PMS2. Conclusions: In the studied population, dMMR tumors more frequently exhibited adverse prognostic features of EC, such as advanced stage of disease and lymphovascular space invasion. This suggests the potential for effective immunotherapy in this patient group. Full article

Objective: Obesity increases the risk of endometrial cancer (EC). In this study, we aimed to investigate the prognostic effect of sarcopenia, sarcopenic obesity and sarcopenic visceral obesity, calculated with the help of cross-sectional imaging methods of muscle and visceral adipose tissue from body composition parameters, in EC. Methods: Patients diagnosed with EC were identified between January 2014 and June 2024. The combination of radiological markers and patient outcomes can predict prognosis. The skeletal muscle index (SMI) and visceral fat index (VFI) were calculated from computed tomography (CT) and/or abdominal magnetic resonance (MR) scans taken at the time of diagnosis at the Lumbal 3 (L3) vertebra level. The findings of these analyses demonstrate the strongest correlation with the ratio of muscle and visceral fat tissue throughout the body. The loss of muscle and fat is an unfavourable indicator in patients with EC. The present study analysed the prognostic values of sarcopenia, sarcopenic obesity, sarcopenic visceral obesity, and the visceral fat index in EC. The total skeletal muscle area was calculated in square centimetres. Body surface area (m²) was calculated using the Mosteller formula: ((height (cm) × weight (kg))/3600)^1/2. To normalize body composition components, the skeletal muscle index was calculated as cm²/m². Results: The study comprised a total of 236 EC patients. The prevalence of sarcopenia, sarcopenic obesity, and sarcopenic visceral obesity were found to be 48.31%, 33.47%, and 22.88%, respectively. The presence of sarcopenia, high VFI levels, sarcopenic obesity, and sarcopenic visceral obesity did not demonstrate statistical significance in the survival analysis. However, stage increase (p = 0.001), primary tumour localization in the lower uterine segment (p = 0.001), serous carcinoma (p = 0.001), increased grade in endometrioid carcinoma (p = 0.023), and lymphovascular invasion (p = 0.001) were significantly associated with increased mortality risk. The presence of sarcopenia was found to be significant in patients with obesity (p = 0.008) and those aged ≥ 65 years (p = 0.001). Conclusions: In EC survival, established prognostic factors such as serous histopathology, LVI positivity, and the extent of surgical staging are prioritised. The presence of these well-established markers means the potential effect of BMI-based observations, such as the ‘obesity paradox’, and even body composition measurements, such as sarcopenic obesity, are now statistically insignificant. Our findings suggest that aggressive tumour biology (serous type, LVI) and surgery, rather than metabolic variables such as sarcopenia, sarcopenic obesity and sarcopenic visceral obesity, are the direct reason for the survival difference. This is due to the tumour’s aggressive nature and clinical characteristics (e.g., age at diagnosis, operability, stage, primary tumour localization in the lower uterine segment, serous carcinoma, grade, and LVI positivity) rather than metabolic variables. Full article

Background/Objectives: Despite advances in targeted therapies, a substantial proportion of high-risk endometrial carcinomas (EC) do not respond to treatment and have a poor prognosis. The identification of prognostic and predictive biomarkers to improve patient stratification is therefore a clinical priority. L1 cell adhesion molecule (L1CAM) is a promising biomarker in EC; however, its soluble circulating form (sL1CAM) has been poorly investigated. This study aimed to evaluate the prognostic and predictive significance of sL1CAM in high-risk ECs. Methods: High-risk EC patients, treated with surgery and platinum-based adjuvant chemotherapy, were retrospectively enrolled. sL1CAM levels were quantified in 72 preoperative serum samples by enzyme-linked immunosorbent assay (ELISA). Results: High sL1CAM levels were associated with advanced age and non-endometrioid histology. Across the entire patient cohort, higher sL1CAM concentrations significantly correlated with worse prognosis in terms of DSS and PFS in univariate (DSS: HR = 2.22, p = 0.028; PFS: HR = 1.21, p = 0.041) and multivariate (DSS: HR = 2.13, p = 0.041; PFS: HR = 1.93, p = 0.048) analyses. Stratification by histological type revealed a significant prognostic association only in the endometrioid subgroup, both in univariate and multivariate analyses. Moreover, in this subgroup, elevated sL1CAM levels were associated with shorter time to recurrence after chemotherapy, both in univariate (PFI: HR = 2.69, p = 0.027) and multivariate (PFI: HR = 2.97, p = 0.017) analysis, and significantly predicted relapse within 6 months (OR = 7.83, p = 0.027). Conclusions: sL1CAM is associated with poor prognosis in high-risk EC and seems to be associated with platinum response in endometrioid tumors. These findings support its potential role as a biomarker to improve risk stratification, warranting validation in larger, prospective studies. Full article

Objectives: Endometrial carcinoma is the most common gynaecological cancer in developed countries, with both incidence and mortality rates continuing to rise globally. For women of reproductive age diagnosed with early-stage disease or endometrial intraepithelial neoplasia, fertility-preserving treatment should be considered to maintain the possibility of future childbearing. Effective fertility-sparing management requires a multidisciplinary approach that includes patient education, reduction in risk factors, accurate molecular and histological classification to guide targeted therapies, assisted reproductive technologies to improve early conception rates, and attention to the psycho-sexual well-being of patients to support treatment adherence. Methods: This retrospective cohort study analysed the clinicopathological features and treatment outcomes of thirteen patients who received fertility-preserving therapy between 2018 and 2023. Results: The mean age of the patients (n = 13) was 34.4 years, with a range of 20 to 41 years. The overall treatment response rate was 76.9%, including 69.2% complete and 7.7% partial responses. Stable disease was observed in 15.4% of cases, while progression occurred in 7.7%. Among those who achieved complete remission, in vitro fertilisation (IVF) was initiated in four cases, with two ongoing as of the time of data analysis. In one of the cases, after two unsuccessful assisted reproductive attempts, spontaneous conception occurred, resulting in the birth of a child. Conclusions: Our findings support the feasibility and success of fertility-preserving treatment in carefully selected patients, allowing the preservation of reproductive potential alongside oncological care. Full article

Endometrial carcinoma is the most frequent gynecologic malignancy in western countries. In recent years, mutations in CTNNB1 have been associated with worse prognosis in low-risk carcinomas. However, there is a lack of understanding of the proteomic implications of CTNNB1 mutations in this type of tumor. In this study, we performed shotgun proteomics using Formalin-Fixed Paraffin-Embedded (FFPE) tissue samples of CTNNB1 mutated and wild-type low-risk endometrial carcinomas. A publicly available proteomic and transcriptomic database was used to validate results. Differential protein expression and Gene Set Enrichment Analysis revealed dysregulation of pathways associated with cell keratinization, immune response modulation, and intracellular calcium regulation. CTNNB1 mutated tumors showed immune dysregulation at multiple levels including cytokine secretion, cell adhesion, and lymphocyte activation. These results were supported by tissue multiplex immunofluorescence analysis, demonstrating reduced CD8 tumor-infiltrating lymphocytes and different immune spatial interaction patterns. Intracellular calcium dysfunction was associated with key transcript dysregulation. We found an increased expression of CAMK2A and ROR2, suggesting a potential role for non-canonical Wnt pathway activation in CTNNB1 mutated tumors. Full article

Background and Objectives: S100A8 regulates inflammatory responses and immune cell activation and is overexpressed in several solid tumors. However, its clinicopathological significance in endometrial carcinoma (EC) remains unclear. This study aimed to evaluate the expression patterns of S100A8 in both tumor and immune cells of EC and examine its association with clinicopathological features. Materials and Methods: Fifty-two formalin-fixed, paraffin-embedded EC specimens were analyzed using tissue microarray-based immunohistochemistry. S100A8 expression was assessed in tumor and immune cells. The tumor proportion score (TPS), tumor staining intensity (TI), and immune proportion score (IPS) were dichotomized into low and high categories (TPS/IPS: ≤30% vs. ≥31%; TI: 0–1+ vs. 2–3+). Correlations with clinicopathological parameters were examined using the chi-square and Fisher’s exact tests. Results: A low TPS, high TI, and high IPS were observed in 51.9%, 63.5%, and 57.7% of patients, respectively. TPS and TI showed no significant correlation with clinicopathological variables, including age, tumor size, invasion depth, histologic grade, T stage, and N stage (all p > 0.05). By contrast, IPS was significantly associated with patients’ age (p = 0.044) and histologic grade (p = 0.012), with older patients and those with higher-grade tumors demonstrating a higher IPS. A positive correlation was observed between TPS and IPS (p = 0.044), whereas TI did not correlate with IPS (p = 0.253). Conclusions: S100A8 expression in immune cells, but not in tumor cells, is associated with age and tumor grade in EC. Therefore, immune-related S100A8 expression may serve as a biomarker of the tumor immune microenvironment, warranting further investigation into its prognostic and therapeutic implications. Full article

Obesity is a major, modifiable driver of endometrial carcinogenesis. This review distills how excess adiposity promotes malignant change and synthesizes prevention strategies across the hyperplasia–cancer continuum. Three converging axes underpin risk: aromatase-mediated estrogen excess; insulin resistance with hyperinsulinemia activating PI3K–AKT–mTOR signaling; and adipokine-driven low-grade inflammation with downstream NF-κB/STAT3 activity. Within this framework, EIN is the key precursor in which these pathways coalesce. Risk can be attenuated through progestin-based therapy (levonorgestrel-releasing intrauterine system or continuous oral regimens), structured weight management, and metabolic adjuncts in selected phenotypes (e.g., metformin for insulin resistance; incretin-based anti-obesity agents as emerging options). Bariatric surgery produces substantial weight loss and favorable metabolic shifts, though evidence for cancer risk reduction is largely observational. Overall, a practical precision-prevention approach—combining progestins with durable weight control and metabolic optimization under guideline-concordant surveillance—appears feasible in routine gynecologic care. Future research should establish causal effects, durability, and optimal sequencing/combination of interventions in trials with endometrial endpoints. Full article

Objectives: Endometrial cancer is the most common gynaecologic malignancy, and its mortality rate is rising. Advanced or recurrent disease remains challenging because historically there have been limited therapeutic options. We aim to describe a complete and durable response to the HER2-directed antibody–drug conjugate trastuzumab deruxtecan (T-DXd) in a heavily pretreated patient with HER2-positive, mismatch-repair-deficient metastatic serous endometrial cancer. Methods: A 72-year-old woman underwent hysterectomy, bilateral salpingo-oophorectomy, and staging procedures for FIGO stage IIIA, high-grade serous papillary endometrial carcinoma. Tumour profiling revealed dMMR, a p53 abnormal pattern, and HER2 overexpression (IHC 3+). She received carboplatin/paclitaxel plus avelumab, followed by pegylated liposomal doxorubicin and weekly paclitaxel. After progression on paclitaxel, off-label T-DXd was initiated. Molecular data (FoundationOne CDx) were collected, along with and serial imaging and CA125 assessments. Results: The patient developed cough after two cycles of T-DXd; interstitial lung disease was excluded, and treatment resumed with steroid cover. By December 2024, PET/CT demonstrated complete metabolic response, with resolution of vaginal-vault and para-aortic lesions and normalisation of CA125. Real-world progression-free survival exceeded eight months, with ongoing symptom improvement. Treatment was generally well tolerated; the principal adverse event was grade 3 neutropenia requiring dose reduction. No cardiotoxicity or interstitial lung disease occurred. Conclusions: This case illustrates that T-DXd can induce deep and durable remission in HER2-positive, dMMR metastatic serous endometrial cancer after multiple lines of therapy. It adds real-world evidence supporting further investigation of HER2-directed antibody–drug conjugates in gynaecologic malignancies, and underscores the need for confirmatory trials and refined biomarker-driven patient selection. Full article

Background/Objectives: Endometrial carcinoma is an emerging challenge for public health systems globally, especially in countries with a high development index. Traditionally, histopathological staging and grading have been the main criteria informing treatment modalities. More recently, clinically actionable molecular targets have been developed, following observations from the TCGA project and the ProMisE cohort. Although promising, the cost of these methods is an obstacle for some countries that lack well developed theranostics infrastructure in their public systems. This study aimed to contextualize our center’s diagnostic experience from the perspective of histopathological diagnosis. Methods: This is a retrospective study that selected 109 cases of already diagnosed endometrial carcinoma from the interval of 2017–2023. We analyzed traditional parameters related to staging and grading, using the FIGO 2009 system as well as basic histological parameters (lymphovascular invasion, perineural invasion, necrosis). Excel and SPSS 26 were used for database management and correlations. Findings were contextualized using the more recent studies that reported on similar parameters. Results: Higher-grade tumors were associated with lymphovascular invasion (p = 0.04) and lymph node involvement (p = 0.0006), as well as deeper myoinvasion (p = 0.0018). Myoinvasion (p = 0.013) and lymphovascular invasion (p = 0.0001) were associated with advanced disease (FIGO III and IV). Our cohort showed a relative paucity (6.5%) of non-endometrioid endometrial carcinoma and presence of lymphovascular invasion (9.2%). Perineural invasion was found in 3 cases with extrauterine involvement. Conclusions: Histopathological diagnosis represents an integral component in informing clinical management for endometrial carcinoma and should serve as a means of triage for more expensive molecular techniques. It nevertheless presents reproducibility issues. Further efforts should focus on resolving such issues or possibly introducing less-researched parameters like perineural invasion. Full article

Cervical cancer is a major global health concern with serious implications for women’s health. It is most often caused by persistent infection with high-risk human papillomavirus (HPV) types. However, about 5–11% of cervical carcinoma cases are HPV-independent, entities with their own unique set of histopathological, molecular, and clinical features. The histopathological forms of HPV-independent cervical cancer include gastric-type adenocarcinoma, clear-cell, mesonephric, and endometrioid carcinoma. Unlike HPV-associated cervical cancers, which require E6 and E7 oncogenes for their expression, HPV-independent tumors exhibit specific mutations such as TP53, PIK3CA, KRAS, STK11, and PTEN. These mutations lead to alternative oncogenic pathways. Diagnosis of HPV-independent cervical adenocarcinoma is often delayed because of possible misclassification as endometrial adenocarcinomas, which frequently results from inadequate HPV testing. This often leads to advanced presentation stages, higher rates of lymphovascular invasion, and, in many cases, a reduced response to chemotherapy and immunotherapy—though outcomes can vary across histotypes and selected patient subgroups—due to the immune-cold tumor microenvironment. Although these morphologic and molecular characteristics describe tumors that are very difficult to manage, PI3K/mTOR and KRAS inhibitors may offer potential therapeutic options for selected patients. This review focuses on the pathogenic and molecular mechanisms, histopathological features, prognosis, and therapeutic difficulties of HPV-independent cervical cancers. Moreover, it provides a comprehension of contemporary issues in diagnostic methods and some new therapeutic approaches, suggesting the need for precision medicine in this aggressive type of cervical cancer. Further studies are necessary to enhance early detection, improve treatment results, and increase survival rates for patients with HPV-independent cervical cancer. Full article

Endometrial carcinoma (EC) is the most common malignancy of the female reproductive tract, with increasing incidence driven by aging populations and obesity. While molecular classification has improved diagnostic precision, the identification of clinically relevant metabolic biomarkers remains incomplete, and targeted therapies are not yet standardized. In this study, we investigated metabolic alterations in four EC cell lines (AN3-CA, EFE-184, HEC-1B and MFE-296) compared to non-malignant controls under normoxic and stress conditions (hypoxia and lactic acidosis) to identify metabolomic differences with potential clinical relevance. Untargeted gas chromatography–mass spectrometry (GC/MS) and targeted liquid chromatography–mass spectrometry (LC/MS) profiling revealed two distinct metabolic subtypes of EC. Cells of metabolic subtype 1 (AN3-CA and EFE-184) exhibited high biosynthetic and energy demands, enhanced cholesterol and hexosyl-ceramides synthesis and increased RNA stability, consistent with classical cancer-associated metabolic reprogramming. Cells of metabolic subtype 2 (HEC-1B and MFE-296) displayed a phospholipid-dominant metabolic profile and greater hypoxia tolerance, suggesting enhanced tumor aggressiveness and metastatic potential. Key metabolic findings were validated via real-time quantitative PCR. This study identifies and characterizes distinct metabolic subtypes of EC within the investigated cancer cell lines, thereby contributing to a better understanding of tumor heterogeneity. The results provide a basis for potential diagnostic differentiation based on specific metabolic profiles and may support the identification of novel therapeutic targets. Further validation in three-dimensional culture models and ultimately patient-derived samples is required to assess clinical relevance and integration with current molecular classifications. Full article

Background/Objectives: To evaluate the clinicopathological features, treatment, and survival outcomes and to identify independent prognosticators for recurrence and mortality in patients with endometrioid ovarian cancer. Methods: The medical records of patients diagnosed with endometrioid ovarian carcinoma between January 2010 and December 2022 were reviewed retrospectively. Demographic and disease-related data were evaluated. Kaplan–Meier survival analysis using log rank test and Cox regression was performed. Results: Seventy-six patients were included in the study. The median age at diagnosis was 54 years (range 31–86). A total of 85.5% of the patients were diagnosed with early-stage disease and 88.1% of the tumours represented low-grade carcinomas. Synchronous endometrioid endometrial cancer was confirmed in 19.7% of the cases. All patients underwent surgical management and 65.8% received adjuvant chemotherapy. Median follow-up time was 67.5 months. The 5-year disease-free survival and overall survival were 92.1% and 93.4%, respectively. The risk of cancer-related death was higher in advanced stages (HR = 13.86; 95% CI 2.16–57.17; p < 0.001) and in the presence of residual disease (HR = 15.18; 95% CI 2.36–87.17; p < 0.002). Residual disease and advanced stages were also identified as independent risk factors for disease relapse with HR = 16.04 (95% CI 2.61–93.7; p < 0.002) and HR = 11.73 (95% CI 1.92–41.6; p < 0.001), respectively. Conclusions: Endometrioid ovarian carcinoma usually affects younger patients with the majority of the cases representing low-grade carcinomas diagnosed at early stages. Residual disease and advanced stages are independently associated with inferior survival outcomes. There was no significance of lymph node dissection and adjuvant chemotherapy in the overall and recurrence-free survival rates. Further research focusing on molecular profiling should aim to define the prevalence and the prognostic value of major molecular alterations and develop precise stratification models to plan personalised treatment for optimal care. Full article

Primary ovarian large cell neuroendocrine carcinoma is an extremely rare and aggressive gynecologic malignancy with poorly defined molecular characteristics and no standard treatment protocols. We present a case of pure ovarian LCNEC in a postmenopausal woman who underwent optimal cytoreductive surgery followed by platinum-based chemotherapy. Histopathologic and immunohistochemical analyses confirmed the diagnosis. Next-generation sequencing (NGS) revealed a pathogenic BRCA2 frameshift mutation (c.7177dupA), an ATM nonsense mutation, and Tier II mutations in TP53 and PTEN. The tumor exhibited homologous recombination deficiency (HRD), microsatellite instability-high (MSI-H), and an exceptionally high tumor mutational burden (TMB) of 277.49 mutations/Mb. These molecular alterations closely resemble those observed in high-grade neuroendocrine carcinomas of cervical and endometrial origin, suggesting a convergent genomic profile across gynecologic neuroendocrine carcinomas (NECs). Our findings underscore the potential of comprehensive genomic profiling in rare tumors such as ovarian LCNEC to refine diagnosis and identify candidates for biomarker-driven therapies, including PARP inhibitors and immune checkpoint inhibitors. This case supports the integration of molecular diagnostics into clinical practice and highlights the need for prospective studies incorporating molecular stratification to inform treatment strategies for rare and aggressive neuroendocrine tumors. Full article

Background: Endometrial proliferative lesions are common in the menopausal transition and carry a measurable risk of carcinoma. Early risk stratification may guide evaluation and follow-up. Methods: We performed a single-center retrospective study of 315 women aged 45–55 years (May 2021–May 2024) at a private clinic in Bucharest. Lesions were classified per WHO 2014 as hyperplasia without atypia, atypical hyperplasia/endometrial intraepithelial neoplasia (AH/EIN), or adenocarcinoma; “advanced pathology” was defined as AH/EIN or adenocarcinoma. Clinical comorbidities and transvaginal ultrasound endometrial thickness were recorded. Associations were tested with χ²; odds were estimated with multivariable logistic regression (adjusted ORs), with a modified Poisson sensitivity analysis for adjusted relative risk. Thickness differences were compared by one-way ANOVA, and severity correlations by Spearman’s ρ. Internal validation used 1000-bootstrap resampling. Results: Hyperplasia without atypia comprised 74.6% of cases, AH/EIN 20.0%, and adenocarcinoma 5.4% (advanced pathology 25.4%). Diabetes was independently associated with advanced pathology (aOR 2.75; 95% CI 1.14–6.61; p = 0.0237), while a history of non-atypical hyperplasia was inversely associated (aOR 0.31; 95% CI 0.13–0.72; p = 0.0068). Obesity showed a borderline association (aOR 1.79; 95% CI 0.98–3.26; p = 0.058), and long-term oral contraceptive use also approached significance (aOR 0.42; 95% CI 0.18–1.00; p = 0.051). Endometrial thickness increased stepwise with histopathological severity (ANOVA p < 0.0001; η² = 0.44) and correlated with ordered severity (ρ = 0.634). The multivariable model showed moderate discrimination (AUC 0.68; optimism-corrected 0.66) with acceptable calibration (slope 0.92; Hosmer–Lemeshow p = 0.052) and overall accuracy (Brier 0.18). Conclusions: In perimenopausal abnormal bleeding, metabolic comorbidities—especially diabetes—together with increased endometrial thickness identify women at higher risk of AH/EIN or carcinoma. Histopathology remains the diagnostic reference. The model can aid clinical prioritization but requires external validation and should not be used as the sole basis for decisions. Full article

Background/Objectives: Endometrial cancer (EC) remains a significant clinical challenge due to increasing incidence and mortality, particularly among patients with TP53 gene mutations, which define a high-risk molecular subtype. This study aimed to characterize the clinicopathological and molecular features of a cohort of patients diagnosed with endometrial cancer and confirmed TP53 mutations. Methods: This retrospective single-center study analyzed 20 patients with histologically confirmed EC and pathogenic TP53 mutations treated at the Pomeranian Medical University Clinical Hospital No. 2 between January 2023 and March 2025. Clinical, histological, and molecular data—including FIGO stage, tumor grade, and coexisting mutations—were collected. Results: Patients had a mean age of 69.2 years and a mean BMI of 29.5 kg/m². The most common histological types were endometrioid (45%) and serous carcinoma (40%). Grade 3 tumors were found in 65% of cases, and 65% of patients exhibited lymphovascular space invasion. Notably, 30% of patients were upstaged under the FIGO 2023 classification when incorporating TP53 mutation status. Four patients had coexisting PIK3CA mutations. No significant differences were observed in BMI, endometrial thickness, or abnormal bleeding between histological subgroups. Conclusions: TP53-mutated endometrial cancers are associated with aggressive histopathological features and advanced staging. Molecular profiling, particularly TP53 mutation assessment, provides essential prognostic information and may inform personalized therapeutic strategies. Larger, multicenter studies are warranted to validate these findings and identify actionable molecular targets. Full article