Search Results (144)

Despite the growing knowledge about ovarian cancer, it has not yet been possible to develop an effective screening test for this cancer. Therefore, it seems necessary to identify new risk factors, such as genetic polymorphisms. The aim of this study was to demonstrate whether polymorphisms of the ESR1 gene rs2234693 and rs9340799 may be involved in the development of ovarian cancer. The material for the study was DNA obtained from 100 ovarian cancer patients and 100 control groups. Polymorphisms were determined using the PCR-RFLP technique. The presence of the CC genotype (rs2234693) has been shown to more than double the risk of ovarian cancer (OR 2.21; p = 0.041). In the case of the second polymorphism, rs9340799, the carrier of the GG genotype more than doubles the risk of ovarian cancer (OR 2.62 p = 0.031). Analysis of ESR1 gene haplotypes in relation to the rs2234693 and rs9340799 polymorphisms showed that the occurrence of TCAG and CCGG systems may be associated with a significant increase in the risk of ovarian cancer (OR 1.98, p = 0.043 and OR 2.45, p = 0.041, respectively). In the group of patients with ovarian cancer, a correlation was shown between the polymorphisms rs2234693 and rs9340799 in the tissues of ovarian cancers with the lowest stage compared to more advanced ovarian cancers, which may indicate a relationship between these factors and the stage of the tumor. Women’s age had no effect on the prevalence of individual genotypes or the associated risk of disease. Polymorphisms rs2234693 and rs9340799 of the ESR1 gene may be associated with the occurrence of ovarian cancer. Full article

The Wuding chicken, a renowned indigenous breed in Yunnan Province, is prized for its superior meat quality; however, its economic potential is limited by pronounced broodiness and suboptimal egg production. Central to alleviating these constraints is the precise regulation of ovarian granulosa cell (GC) proliferation and steroidogenic processes that dictate follicular development and laying performance. While Estrogen Receptor 2 (ESR2) is a known transcription factor implicated in follicular maturation, its spatiotemporal dynamics within the hypothalamic-pituitary-ovarian (HPO) axis and its specific regulatory mechanisms in Wuding chicken remain elusive. This study characterizes ESR2 expression across the HPO axis during the laying and broody periods and functionally validates its role in GCs. We observed that ESR2 expression was significantly higher throughout the HPO axis during the laying period compared to the broody period, with the most pronounced differential expression occurring in the ovary. Notably, subcellular localization analysis revealed that ESR2 is distributed in both the nucleus and the cytoplasm, indicating involvement in both nuclear transcriptional regulation and cytoplasmic signaling. Functional assays demonstrated that ESR2 modulates the expression of genes associated with GC proliferation, steroidogenesis, and apoptosis, involving the PI3K/AKT/mTOR signaling pathway. Our findings indicate that this process involves a synergistic interplay between genomic and potential non-genomic actions. Specifically, ESR2 overexpression upregulates the expression of key signaling components and steroidogenic genes, including CYP19A1, STAR, PTGS2, and FSHR, while its cytoplasmic localization suggests a role in non‑genomic interactions. Together, these coordinated mechanisms synergistically maintain GC functional homeostasis. Collectively, these results prove that ESR2 plays an important role in regulating GC homeostasis and follicular development through genomic and non-genomic modes of action. These findings provide a molecular basis for the role of ESR2 in avian follicular development and offer potential targets for improving the reproductive efficiency of Wuding chickens. Full article

Background/Objectives: Patients admitted to intensive care units (ICUs) are confronted with complex clinical situations that impact their physical condition and psychological well-being. Psycho-emotional disorders such as pain, anxiety and post-traumatic stress are highly prevalent in this context, significantly affecting both the patient’s experience and the quality of care provided. Effective communication can help manage patients’ psycho-emotional states and prevent post-ICU disorders. To evaluate the effectiveness of the CONECTEM communicative intervention in improving the psycho-emotional well-being of critically ill patients admitted to the intensive care unit, regarding pain, anxiety, and post-traumatic stress symptoms. Methods: A quasi-experimental study employed a pre–post-test design with both a control group and an intervention group. The study was conducted in two ICUs in a tertiary Hospital in Spain. A total of 111 critically ill patients and 180 nurse–patient interactions were included according to the inclusion/exclusion criteria. Interactions were classified according to the level of the patient’s consciousness into three groups: G1 (Glasgow 15), G2 (Glasgow 14–9), and G3 (Glasgow < 9). Depending on the patient’s communication difficulties, nurses selected one of three communication strategies of the CONECTEM intervention (AAC low teach, pictograms, magnetic board, and musicotherapy). Pain was assessed using the VAS or BPS scale, anxiety using the STAI, and symptoms of PTSD using the IES-R. The RASS scale was utilized to evaluate the degree of sedation and agitation in critically ill patients receiving mechanical ventilation. Data analysis was performed using repeated ANOVA measures for the pre–post-test, as well as Pearson’s correlation test and Mann–Whitney U or Kruskal–Wallis statistical tests. Results: The results showed pre–post differences consistent with pain after the intervention in patients with Glasgow scores of 15 (p < 0.001) and 14–9 (p < 0.001) and in anxiety (p = 0.010), reducing this symptom by 50% pre-test vs. 26.7% post-test. Patients in the intervention group with levels of consciousness (Glasgow 15–9) tended to decrease their post-traumatic stress symptoms, with reductions in the mean IES scale patients with a Glasgow score of 15 [24.7 (±15.20) vs. 22.5 (±14.11)] and for patients with a Glasgow score of 14–9 [(Glasgow 14–9) [30.2 (±13.56) 27.9 (±11.14)], though this was not significant. Given that patients with a Glasgow score below 9 were deeply sedated (RASS-4), no pre–post-test differences were observed in relation to agitation levels. Conclusions: The CONECTEM communication intervention outcomes differed between pre- and post-intervention assessments in patients with a Glasgow Coma Scale score of 15–9 regarding pain. These findings are consistent with a potential benefit of the CONECTEM communication intervention, although further studies using designs that allow for stronger causal inference are needed to assess its impact on the psycho-emotional well-being of critically ill patients. Full article

Background: Fibromyalgia syndrome (FMS) and post-traumatic stress disorder (PTSD) may co-occur and are associated with increased symptom burden, functional impairment, and reduced quality of life. Accumulating evidence suggests shared neurobiological mechanisms. Trauma-focused interventions targeting maladaptive memory processes may therefore represent a relevant therapeutic approach in this population. Objective: To evaluate the feasibility, tolerability, and preliminary clinical associations of a brief reconsolidation-based therapy in women with comorbid FMS and PTSD. Methods: This multicenter pilot study included adult women diagnosed with FMS and PTSD who underwent six sessions of reconsolidation therapy combining traumatic memory reactivation with propranolol administration. Clinical outcomes were assessed at baseline and at 3-month follow-up using the Fibromyalgia Impact Questionnaire (FIQ), the Impact of Event Scale–Revised (IES-R), the Montgomery–Åsberg Depression Rating Scale (MADRS), the Beck Depression Inventory (BDI), the Rosenberg Self-Esteem Scale (RSES), and the SF-36. Changes over time were analyzed using paired statistical tests and linear mixed-effects models. Results: Fourteen participants completed the intervention and follow-up assessments. The intervention was feasible and well tolerated. Changes over time were observed in fibromyalgia-related quality of life (FIQ scores), PTSD symptom severity (IES-R), and depressive symptoms (MADRS, BDI), as well as in selected SF-36 domains, including vitality, social functioning, and mental health. A progressive decrease in IES-R scores was observed across treatment sessions. Conclusions: This pilot study suggests that reconsolidation-based therapy is feasible in women with comorbid FMS and PTSD and was associated with changes in PTSD symptoms and fibromyalgia-related functional impact. Given the exploratory design and absence of a control group, these findings should be interpreted cautiously and warrant confirmation in larger, controlled trials. Full article

The COVID-19 pandemic exposed the fragility of global health systems, as physicians faced extremely challenging conditions including excessive workloads, infection risk, and high patient mortality. We conducted a cross-sectional survey that aimed to assess the post-pandemic prevalence of anxiety, depression, and post-traumatic stress disorder (PTSD) in a sample of Greek physicians who worked on the frontline during the SARS-CoV-2 (COVID-19) pandemic. An online survey was conducted between 1 March and 31 July 2023, in which 200 Greek physicians were invited via e-mail to voluntarily answer a confidential online questionnaire, and 58 of them responded. The survey included two clinically validated tools: the Patient Health Questionnaire-4 (PHQ-4) and the Impact of Event Scale—Revised (IES-R). Univariate correlations of 26 exposure variables with anxiety, depression, combined anxiety/depression, and PTSD were performed. In total, 58 eligible physicians (46.6% female) participated in this study. The rates of anxiety, depression, combined anxiety/depression, and PTSD were 27.5% (95% CI: 16.7–40.9), 31.0% (19.5–44.5), 22.4% (12.5–35.3), and 24.1% (13.9–37.2), respectively. Notably none of the physicians working in a laboratory developed any mental health symptoms. The following factors were found to be associated with the development of higher mental health symptoms: age ≤ 30, employment in healthcare ≤ 10 years, working in COVID-19 wards, working in intensive care units or COVID-19 wards, a history of mental health symptoms, a history of physical conditions, shortages of materials and equipment for diagnosing or treating patients, development of a disease other than COVID-19, and the development of a new mental health condition during the pandemic (p < 0.05 for all associations). Our findings highlight the need to better prepare physicians with adequate materials, infrastructure, and psychological support such that, in a potential future health crisis, they will not be at such high risk of mental health problems. Full article

Objective: This pilot study assessed the psychological and physical impact of the COVID-19 pandemic on postpartum women that gave birth during the pandemic, and evaluated the feasibility of remote monitoring for maternal mental health. The study also proposes a conceptual framework to strengthen remote maternal care in future public health emergencies. Methods: Conducted between 2020 and 2021 in Reggio Emilia, one of Italy’s ten hardest-hit provinces during the early COVID-19 outbreak, this study enrolled 21 pregnant women (10 COVID-19-positive at delivery, 11 COVID-19-negative controls). Psychological and physical health were assessed using validated instruments: the Beck Depression Inventory (BDI) and Edinburgh Postnatal Depression Scale (EPDS) for depression, the State-Trait Anxiety Inventory (STAI) for anxiety, the Impact of Event Scale–Revised (IES-R) for trauma-related stress, and the SF-36 for physical functioning. Additional measures included breastfeeding experience and resilience. Remote assessments were conducted between 6 and 12 months postpartum to evaluate psychological recovery and satisfaction with perinatal care. C test was used to compare the two groups of women. Results: COVID-19-positive women reported significantly higher depressive symptoms (BDI: 13.50 ± 8.14 vs. 6.73 ± 4.73; U = 27, p = 0.048), and elevated state anxiety levels (STAI-S: 41.60 ± 10.23 vs. 33.64 ± 10.15; U = 27, p = 0.048) compared to controls. Post-traumatic stress symptoms were also higher among COVID-positive participants (IES-R total: 41.10 ± 19.33 vs. 30.64 ± 7.99; U = 24.5, p = 0.029). No significant differences emerged in EPDS or trait anxiety scores. Conclusions: Remote data collection proved feasible for postpartum women during the pandemic and highlighted elevated depressive, anxiety, and trauma-related symptoms in COVID-19-positive mothers. These findings support the development of flexible digital care frameworks for maternal well-being in crises. The introduction of the “10 Gold Rules for Remote Maternal Healthcare in Critical Situations” offers a forward-looking, expert-informed conceptual framework to guide the development of scalable, trust-based digital care models that go beyond monitoring to include proactive, patient-centred support. Full article

Background: The ESR2 gene encodes Estrogen Receptor-β1 (ERβ1), a putative tumor suppressor in hormone-dependent malignancies. Although ERβ biology has been studied extensively at the expression level, the functional impact of nonsynonymous SNPs (nsSNPs) and untranslated-region (UTR) variants in ESR2 remains underexplored. Methods: We retrieved variants from Ensembl and performed an integrative in silico assessment using PredictSNP, I-Mutant, MUpro, HOPE, MutPred2, and CScape for pathogenicity, oncogenicity and structural stability; STRING/KEGG/GO for pathway context; RegulomeDB and polymiRTS for regulatory effects; and cBioPortal for pan-cancer clinical outcomes (breast (BRCA), endometrial (UCEC), and ovarian (OV)). We evaluated effects of nsSNPs on ERβ1 stability, ligand-binding/DNA-binding domains, co-factor recruitment, and post-transcriptional regulation. Results: Across tools, 93 missense nsSNPs were consistently predicted to be deleterious. Notably, several variants were found to destabilize ERβ1, particularly within the ligand-binding domains (LBD) and DNA-binding domains (DBD). Putative oncogenic drivers R198P and D154N showed high CScape scores and very low population frequencies, consistent with pathogenicity. Several substitutions were predicted to impair coactivator binding and disrupt interactions with key transcriptional partners, including JUN, NCOA1, and SP1. At the post-transcriptional level, rs139004885 was predicted to disrupt miRNA binding, while 3′UTR rs4986938 showed strong regulatory potential and comparatively high population frequency; by contrast, most other identified SNPs were rare. Clinically, pan-cancer survival analyses indicated worse overall survival (OS) in BRCA for ESR2-Altered cases (HR ≈ 2.25; q < 0.001), but better OS in UCEC (HR ≈ 0.24; q ≈ 0.014) and OV (HR ≈ 0.29; q < 0.001), highlighting a tumor-type-specific association. Conclusions: This integrative analysis prioritizes high-impact ESR2 variants that likely impair ERβ1 structure and shows context-dependent clinical effects. Despite their generally low frequency (except for rs4986938), prospective validation linking variant class to ERβ expression and survival outcomes is needed to support biomarker development and therapeutic applications. Full article

Background: This study explores post-traumatic growth (PTG) among parents of childhood cancer survivors (CCSs), a group often underrepresented in research. Method: A convergent parallel mixed-methods design integrating Bayesian Multilevel Latent Class Analysis and Thematic Analysis was utilized in a longitudinal study involving 58 caregivers (50 mothers, 8 fathers) from the Children’s Clinical University Hospital in Riga. Quantitative data were collected at diagnosis using the Psychosocial Assessment Tool (PAT) and Big Five Inventory-10 (BFI-10). Follow-up assessments post-treatment included the Responses to Stress Questionnaire (RSQ), Impact of Event Scale-Revised (IES-R), and the Post-traumatic Growth Inventory (PTGI). Qualitative data were collected through structured interviews. Results: A 2-class model distinguished parents with low PTG from those with moderate to high PTG. Change in values, detachment from trivial stressors, and acceptance of life emerged as key indicators of growth. PTG was not significantly correlated with overall post-traumatic stress symptoms, but engagement coping strategies showed a positive association with PTG and personality traits like extraversion and openness. Conclusions: The mixed methods approach revealed sample-specific PTG elements not reflected in standardized tools. Initial perceptions of the cancer diagnosis shaped psychological outcomes, with PTG facilitated by adaptive coping, self-reflection, support, emotional disclosure, and psychological struggle. This study offers the first insights into PTG among Latvian parents of CCSs, a previously unexplored area. Full article

Background: COVID-19 has been associated with multisystemic sequelae, including persistent neurocognitive impairment and emerging metabolic alterations. Growing evidence suggests that glial dysfunction and inflammation may play a pivotal role in both cognitive decline and new-onset diabetes following SARS-CoV-2 infection. Objectives: This study aimed to assess the prevalence and characteristics of cognitive impairments in post-COVID-19 patients and to explore their correlation with new-onset diabetes, neuroanatomical changes, and psychological symptoms, with a specific focus on gender differences. Methods: A total of 245 patients (mean age 56.8 ± 12 years), previously diagnosed with COVID-19, were enrolled between April 2021 and August 2023. Participants underwent a comprehensive neuropsychological assessment (MMSE, Rey-Osterrieth Figure, FAB, Hamilton, STAI, IES-R), structured interviews, and, in a subset, brain MRI. Individuals with pre-existing neurological disorders were excluded. Data were analyzed for cognitive performance, neuroimaging abnormalities, and metabolic outcomes, including new-onset diabetes. Results: Cognitive dysfunction was identified in 87% of participants: mild in 47%, moderate in 21.6%, and severe in 10.8%. Glial alterations on MRI were observed in 51%, hippocampal atrophy in 9%, and temporal lobe reduction in 4%. Notably, 12% of patients developed new-onset diabetes post-COVID, of whom 80% exhibited mild to moderate cognitive deficits. Depressive symptoms were present in 80.9%, and anxiety in 93.5%, with significantly higher incidence in female patients. PTSD symptoms correlated with greater cognitive impairment. Ongoing research into the mechanisms underlying these persistent cognitive impairments in subjects with and without types 1 and 2 diabetes. This paper presents the final data of the research published in the previous article referenced in the bibliography. Conclusions: This study highlights a significant association between cognitive decline and new-onset diabetes in post-COVID patients, likely mediated by systemic inflammation and glial dysfunction. Particularly noteworthy are the findings of neuroanatomical alterations, including nonspecific glial signal changes, hippocampal atrophy, and temporal lobe volume reductions, suggesting post-infectious cerebral vulnerability with potential long-term consequences. These results support the need for integrating cognitive screening, brain neuroimaging, and metabolic monitoring into post-COVID care pathways—especially for women and individuals presenting with anxiety or depressive symptoms. An early and interdisciplinary approach is essential to address the neuro-metabolic and cerebral sequelae of long COVID. Full article

Background: Severe burn injuries often lead to lasting physical and psychological consequences. Post-traumatic stress disorder (PTSD) is common among burn survivors and may be influenced by persistent somatic complaints. This study examined whether PTSD is associated with a higher burden of physical symptoms during and after inpatient rehabilitation. Methods: We conducted a subgroup analysis of a multicenter prospective cohort study involving 103 adult burn patients in inpatient rehabilitation. Based on Impact of Event Scale—Revised (IES-R) scores and clinical evaluation, patients were grouped as PTSD (n = 43) or No PTSD (n = 60). Physical symptoms assessed included skin dryness (xerosis), temperature sensitivity (cold/heat), numbness, skin tightness, and increased sweating. Results: Patients with PTSD reported significantly more physical symptoms at follow-up than those without PTSD: xerosis (74% vs. 50%, p = 0.03), cold sensitivity (61% vs. 35%, p = 0.02), heat sensitivity (63% vs. 39%, p = 0.03), numbness (63% vs. 33%, p = 0.006), skin tightness (82% vs. 52%, p = 0.004), and sweating (45% vs. 19%, p = 0.01). PTSD patients also had more severe burns, reflected in higher full-thickness TBSA (2% vs. 0%, p = 0.03) and elevated ABSI scores (median 6 vs. 5, p = 0.04). Conclusion: PTSD is associated with a higher and more persistent burden of physical skin symptoms after severe burns. These findings underscore the importance of early PTSD screening and integrated psychological-somatic rehabilitation to improve long-term recovery and quality of life. Full article

Background/Objectives: Both traumatic and stressful events, including major life changes, may contribute to post-traumatic stress symptoms (PTS), often associated with anxiety and depression. Feelings of loneliness may influence these relationships, whilst social support seems to mitigate the effects of stressful events on mental health. Our study thus aimed to evaluate the mediating role of loneliness in the relationships between PTS and both anxiety and depressive symptoms among university students. Methods: The data were from the CAMPUS study (0058642/21; FHMS 20-21 157), a survey on university students’ mental health in Italy and the UK. Using a logit model, mediation analyses were carried out to test whether the relationships between PTS and both anxiety and depressive symptoms might be mediated by loneliness. A path analysis was then performed to jointly test the associations between the Impact of Event Scale—Revised (IES-R)’s subscales and clinical domains. Results: Positive associations were found between PTS and both anxiety (p < 0.001) and depressive symptoms (p < 0.001). However, loneliness mediated approximately 22% of the effect of the PTS on anxiety symptoms (indirect effect: 1.04, 95% CI: 0.59; 1.48, p < 0.001) and approximately 33% of the effect of the PTS on depressive symptoms (indirect effect: 1.81, 95% CI: 1.22; 2.39, p < 0.001). Furthermore, the path analysis indicated associations between the IES-R’s hyperarousal subscale and both anxiety (coeff.: 0.34, p < 0.001) and depressive symptoms (coeff.: 0.27, p < 0.001). Conclusions: Along with the associations between PTS and both anxiety and depressive symptoms, our findings highlight the key role of loneliness in both these associations. Targeted interventions to reduce loneliness, especially for students exposed to traumatic events, may ultimately improve their mental health. Full article

Background/Objectives: Most survivors of out-of-hospital cardiac arrest (OHCA) may suffer from cognitive, mental difficulties, and fatigue, which negatively impact their quality of life, despite a good physical recovery. However, no definitive data are available on this topic, so this study aims to assess the feasibility and acceptability of a centralized, sub-regional screening system for OHCA survivors in Italy and the prevalence of these disorders. Methods: OHCA survivors discharged with good neurological outcomes (Cerebral Performance Category (CPC) ≤ 2 and modified Ranking Scale (mRS) ≤ 3) from hospitals in the “Lombardia CARe” registry will be evaluated by a clinical psychologist using the Montreal Cognitive Assessment (MoCA), Hospital Anxiety and Depression Scale (HADS), EQ-5D-5L for quality of life, and the Impact of Event Scale-Revised (IES-R) at pre-discharge or within 15 days and then at 1, 3, 6, and 12 months. Patients with clinical issues will be referred for psychological support or to a community rehabilitation program. Feasibility will be defined as a recruitment rate ≥ 80% and acceptability as a retention rate ≥ 50% over 12 months. Results: Based on historical data from the Lombardia CARe, an estimated 350 eligible survivors are expected, which will allow estimation of a prevalence ranging between 20% and 30% with 5% precision and 95% confidence. Conclusions: This study will be the first in Italy to evaluate the feasibility and acceptability of a centralized, sub-regional system for pre-/post-discharge evaluation of cognitive impairment, mental health, and quality of life in a large cohort of OHCA survivors, documenting the prevalence of these disorders. Full article

Background: ESR1 mutations are biomarkers in breast cancer patients who develop metastatic disease after endocrine therapy (ET). Recently, the Food and Drug Administration (FDA) and European Medicines Agency (EMA) have approved Elacestrant, a selective estrogen receptor degrader for patients harboring ESR1 mutations. This has necessitated the establishment of reliable and sensitive NGS- or PCR-based assays to detect these ESR1 resistance mutations in liquid biopsy samples. Methods: We evaluated NGS results of a pan-cancer cohort of almost 6000 patients from two major German institutes of pathology, to show that the occurrence of ESR1 mutations is extremely rare (<1%) in ET-naïve patients. This suggests that ESR1 mutations arise almost exclusively under the pressure of ET. Therefore, we designed a breast cancer-specific hybrid capture-based NGS liquid biopsy assay covering 12 breast cancer-related genes, including ESR1, PIK3CA, AKT1, ERBB2, BRCA1/2, and TP53. We validated the HS2-Mamma-LIQ assay extensively using reference material to detect mutations to 0.1% variant allele frequency (VAF) and compared the performance to a commercially available ESR1 ddPCR assay. Results: We show the results of routine diagnostic analysis of the first consecutive 354 patients with activating ESR1 mutations rate of 43%, with 20% of patients harboring co-mutations in PIK3CA and other genes underlining the relevance of tumor heterogeneity. Our study highlights liquid biopsy as a preferred approach for monitoring ESR1 mutations in breast cancer patients by showing cases where NGS analysis suggests complex tumor heterogeneity with multiple ESR1 as well as PIK3CA mutations at different VAFs. Conclusions: Our findings not only corroborate prior research concerning the rarity of these mutations in unselected patients but also emphasize the importance of robust and broad molecular assays rather than single gene assays in their detection and characterization in the diagnostic setting. Advantages of different approaches are discussed to address the current clinical need. Full article

Breast cancer (BC) is a multifactorial condition and it primarily expresses the estrogen receptor α (ERα) that is encoded by the gene estrogen receptor 1 (ESR1), which modulates estrogen signaling. ESR1, by facilitating estrogen overproduction, plays an indispensable role in the progression and survival of the majority of BCs. To obtain molecular insights into these phenomena, we analyzed The Cancer Genome Atlas (TCGA) breast invasive carcinoma (BRCA) RNA-Seq datasets for the expression of ESR1 and its correlation to microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), along with its methylation patterns. Regulation of ESR1 was also assessed with a total of 43 cancerous and non-cancerous breast cell lines. Analyses of both TCGA BRCA and breast cell line RNA-Seq data revealed that specific lncRNAs, i.e., MEG3, BIK, MLL, and FAS are negatively correlated with the ESR1, in which PARP1 demonstrates a positive association. Additionally, both miR-30a and miR-145 showed negative correlations with the ESR1 expression. Of the 54 ESR1 methylation loci analyzed, the majority of them exhibited a negative correlation with the ESR1 expression, highlighting a potentially modifiable regulatory mechanism. These findings underscore the complex regulatory events influencing ESR1 expression and its interaction with diverse signaling pathways, demonstrating novel insights into breast pathogenesis and its potential therapeutics. Full article

Introduction: Among uterine tumors resembling ovarian sex cord tumors (UTROSCTs), it has been suggested that GREB1-rearranged cases are biologically distinct from ESR1-rearranged cases and might be considered as a separate entity. Objectives: The aim of this systematic review was to assess the difference between GREB1- and ESR1-rearranged UTROSCTs with regard to several clinico-pathological parameters. Methods: Three electronic databases were searched from their inception to February 2025 for all studies assessing the presence of GREB1 and ESR1 rearrangements in UTROSCTs. Exclusion criteria comprised overlapping patient data, case reports, and reviews. Statistical analysis was performed to compare clinicopathological variables between GREB1- and ESR1-rearranged UTROSCTs. Dichotomous variables were compared by using Fisher’s exact test; continuous variables were compared by using Student’s t-test. A p-value < 0.05 was considered significant. Results: Six studies with 88 molecularly classified UTROSCTs were included. A total of 36 cases were GREB1-rearranged, and 52 cases were ESR1-rearranged. GREB1-rearranged UTROSCTs showed a significantly older age (p < 0.001), larger tumor size (p = 0.002), less common submucosal/polypoid growth (p = 0.005), higher mitotic index (p = 0.010), more common LVSI (p = 0.049), and higher likelihood to undergo hysterectomy (p = 0.008) compared to ESR1-rearranged cases. No significant differences were detected with regard to margins, cytological atypia, necrosis, retiform pattern, and rhabdoid cells. No significant differences were found in the immunohistochemical expression of any of the assessed markers (wide-spectrum cytokeratins, α-inhibin, calretinin, WT1, CD10, CD56, CD99, smooth muscle actin, desmin, h-caldesmon, Melan-A/MART1, SF1, or Ki67). GREB1-rearranged UTROSCTs showed significantly lower disease-free survival compared to ESR1-rearranged UTROSTCs (p = 0.049). Conclusions: In conclusion, GREB1-rearranged UTROSCTs occur at an older age, are less likely to display a submucosal/polypoid growth, and exhibit larger size, a higher mitotic index, more common lymphovascular space invasion, and lower disease-free survival compared to ESR1-rearranged UTROSCTs. Nonetheless, the similar immunophenotype suggests that they belong to the same tumor family. Further studies are necessary to confirm this point. Full article