Stromal Invasion Research Articles

NEDD4 Knockdown Suppresses Human Endometrial Stromal Cell Growth and Invasion by Regulating PTGS2-Mediated Ferroptosis in Endometriosis.

Endometriosis (EM) is a gynecological disease characterized by the benign growth of endometrial tissue outside the uterus. Upregulation of neuronally expressed developmentally downregulated 4 (NEDD4) has been reported to accelerate endometrial cancer progression. We explored whether abnormal expression of NEDD4 is correlated with EM. Endometrial tissue in patients without endometriosis was used to develop the original generation of endometrial stromal cells (ESCs). Different types of endometrial tissue of patients with endometriosis were used to measure the expression of NEDD4 by immunohistochemistry (IHC) and western blotting. Its biological functions in ESCs were investigated using a cell counting kit-8 assay, fluorescein diacetate (FDA) staining, and Transwell invasion assays. Additionally, its involvement in ferroptosis was assessed by measuring Fe2+, malondialdehyde (MDA), glutathione (GSH), and reactive oxygen species (ROS) levels and the expression of ferroptosis markers. Compared with normal controls, NEDD4 levels were significantly elevated in the endometrial tissue of patients with EM. Furthermore, NEDD4 expression was higher in the ectopic endometrium than in the eutopic endometrium. NEDD4 knockdown reduced the viability and invasive capacity of ESCs, increased Fe2+, MDA, and ROS levels, and decreased GSH content. Further analysis revealed that NEDD4 knockdown promoted ferroptosis in ESCs by increasing the expression of prostaglandin-endoperoxide synthase 2 (PTGS2). As an E3 ubiquitin ligase, NEDD4 reduced PTGS2 protein levels by accelerating its ubiquitination and subsequent proteasomal degradation. These findings suggest that inhibiting NEDD4 reduces ESC growth and invasion in EM by regulating PTGS2-dependent ferroptosis.

The Accuracy of Arterial Phase of Dynamic Contrast-Enhanced Magnetic Resonance Imaging in Predicting Cervical Stromal Invasion in Patients with Endometrial Carcinoma

Background: Endometrial cancer is the most common gynecological cancer. Cervical stromal invasion in patients with endometrial carcinoma is associated with local recurrence and overall survival, making accurate preoperative evaluation essential. Currently, the delayed phase of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is recommended for diagnosing cervical stromal invasion. However, this approach is time-consuming, and diagnostic interpretations can vary across observers and institutions. Objectives: To compare the diagnostic accuracy of arterial-phase and delayed-phase DCE-MRI for detecting cervical stromal invasion in endometrial carcinoma. Patients and Methods: This cross-sectional study retrospectively collected data from 445 patients with endometrial cancer. Two radiologists jointly evaluated cervical stromal invasion using histopathology as the gold standard reference. The McNemar test was used to compare the sensitivity and specificity of cervical stromal invasion detection between the arterial and delayed phases of DCE-MRI. Logistic regression analysis was conducted to assess the impact of tumor location and cervical lesions on diagnostic accuracy for cervical stromal invasion using DCE-MRI. Results: The mean age of the study population was 53.5 years [standard deviation (SD) = 3.1]. Dynamic contrast-enhanced magnetic resonance imaging images of the cervix demonstrated distinct enhancement characteristics. For detecting cervical stromal invasion, arterial-phase DCE-MRI showed a sensitivity of 66.4% [95% confidence interval (CI): 60.0 - 74.6%] and a specificity of 87.9% (95% CI: 83.9 - 91.0%). In the delayed phase, sensitivity was 69.1% (95% CI: 60.0 - 77.1%) and specificity was 88.2% (95% CI: 84.3 - 91.2%). There was no statistically significant difference between the arterial and delayed phases (P = 1.00). Factors influencing the assessment of cervical stromal invasion included the cluster distribution of Nabothian cysts and lesions located in the lower uterine segment or the internal os (P = 0.01, P < 0.01). Conclusion: The arterial phase of DCE-MRI is a feasible, time-saving, and effective approach for detecting cervical stromal invasion in endometrial carcinoma.

Characterization of E-Cadherin, SSEA-1, MSI-1, and SOX-2 Expression and Their Association with Pale Cells in Adenomyosis

Adenomyosis (AM) is a gynecological disease characterized by the invasion of endometrial glands and stroma within the myometrium. The etiology and pathogenesis of AM remain inadequately understood. Pale cells were identified as a novel cell type characterized by the absence of desmosomal contacts and light-colored cytoplasm. These cells were observed to migrate individually through ultra-micro ruptures in the basal membrane of the endometrial glands, translocating into the stroma and then further into the myometrium. Our study aimed to explore the possible stem cell properties of these pale cells. Forty hysterectomy specimens were analyzed using immunohistochemistry and immunofluorescence to assess negative E-cadherin expression and the positive expression of stem cell markers SSEA-1, MSI-1, and SOX-2. Immunohistochemical analysis revealed the presence of pale cells and occasionally rounded, enlarged E-cadherin-negative cells predominantly in the basal endometrial epithelium. The stem cell marker SSEA-1 was significantly elevated in the basalis epithelium, as well as in the ectopic epithelium. SSEA-1 positive cells were also identified in the stroma and myometrium. Sporadic colocalization of SSEA-1+/E-cadherin– cells was confirmed through immunofluorescence. The positive staining of pale cells for SSEA-1 and MSI-1 was also confirmed at the ultrastructural level by immunoelectron microscopy. These findings indicate that pale cells may possess stem cell characteristics, particularly a positive SSEA-1 profile, warranting further in vitro investigation into their role in the pathogenesis of adenomyosis.

Inhibiting SNX10 induces autophagy to suppress invasion and EMT and inhibits the PI3K/AKT pathway in cervical cancer.

Cervical cancer (CC) is a prevalent malignancy among women with high morbidity and poor prognosis. Sorting nexin 10 (SNX10) is a newly recognized cancer regulatory factor, while its action on CC progression remains elusive. Hence, this study studied the effect of SNX10 on CC development and investigated the mechanism. The SNX10 level in CC and the overall survival of CC cases with different SNX10 expressions were determined by bioinformatics analysis in GEPIA. The SNX10 expression in tumor tissues and clinical significance were studied in 64 CC cases. The overall survival was assessed using Kaplan-Meier analysis. The formation of LC3 was evaluated using immunofluorescence. Cell invasion was measured using the Transwell assay. Epithelial-to-mesenchymal transition (EMT) was determined by observing cell morphology and assessing EMT marker levels. A xenograft tumor was constructed to evaluate tumor growth. SNX10 was elevated in CC tissues and cells, and the CC cases with high SNX10 levels exhibited poor overall survival. Besides, SNX10 correlated with the FIGO stage, lymph node invasion, and stromal invasion of CC. SNX10 silencing induced CC cell autophagy and suppressed CC cell invasion and EMT. Meanwhile, silenced SNX10 could suppress invasion and EMT via inducing autophagy. Furthermore, SNX10 inhibition suppressed the PI3K/AKT pathway. Moreover, silenced SNX10 restrained the tumor growth, autophagy, and EMT of CC in vivo. SNX10 was enhanced in CC and correlated with poor prognosis. Silenced SNX10 induced autophagy to suppress invasion and EMT and inhibited the PI3K/AKT pathway in CC, making SNX10 a valuable molecule for CC therapy.

Adenomyosis and fibrosis define the morphological memory of the postpartum uterus of dairy cows previously exposed to metritis.

Optimal fertility after calving in lactating dairy cows is dependent upon the successful completion of uterine involution. Invasion of pathogenic bacteria into the uterine environment within the first week postpartum can lead to uterine disease (metritis). Metritis is associated with decreased fertility and a failure or delay in establishing pregnancy. We hypothesized that early postpartum metritis would be associated with long-term changes in uterine morphology that begin within the first 30 d postpartum (dpp) and are present during a typical breeding window (2–6 mo postpartum). First parity Holstein cows were diagnosed with metritis (M) or deemed healthy (H) at 7 to 10 dpp and uterine tissues were collected and analyzed post-mortem at 30 (Exp. 1; M = 10, H = 10), or 80 and 165 (Exp. 2; M = 9, H = 10) dpp for the presence of abnormal morphology, including abnormal invasion of endometrial glands and stroma into the myometrium (adenomyosis) and endometrial fibrosis. Glands were identified using immunohistochemistry for FOXA2 (uterine gland specific marker) and fibrosis was identified using mason's trichrome stain (MTS). The severity of adenomyosis was assessed by the number and size of adenomyotic foci and the distance of foci from the endometrium-myometrium interface (EMI). The degree of fibrosis was defined by MTS intensity. Data were analyzed using a 2-way ANOVA procedure including the effect of metritis and dpp on dependent variables foci size, distance from EMI, and MTS intensity. A negative binomial regression model was utilized for the dependent variable of foci number. The presence, size, and distance from the EMI of adenomyotic foci were greater for later postpartum (Exp. 2, 80 and 165 dpp) and early postpartum cows (Exp. 1, 30 dpp) that were previously diagnosed with metritis, suggesting greater severity of adenomyosis. Endometrial fibrosis was greater at the stratum basalis (near EMI) compared with the stratum compactum endometrium (near uterine lumen) for all Exp. 2 (80 and 165 dpp) cows. Greater fibrosis (regardless of endometrial region) was observed in cows diagnosed with metritis compared with healthy controls. Taken together, these data indicate that early postpartum metritis is associated with long-term changes to postpartum uterine morphology, including increased pathological fibrogenesis, leading to the presence of late postpartum endometrial fibrosis (scar tissue), and aberrant endometrial invasion into the myometrium (adenomyosis). Additionally, increased collagen fiber at the EMI suggests a correlation between the development of adenomyosis and fibrosis, which could result from sustained endometrial inflammation caused by uterine disease.

Multiparametric MRI-based radiomics combined with 3D deep transfer learning to predict cervical stromal invasion in patients with endometrial carcinoma.

To develop and compare various preoperative cervical stromal invasion (CSI) prediction models, including radiomics, three-dimensional (3D) deep transfer learning (DTL), and integrated models, using single-sequence and multiparametric MRI. Data from 466 early-stage endometrial carcinoma (EC) patients from three centers were collected. Radiomics models were constructed based on T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) mapping, contrast-enhanced T1-weighted imaging (CE-T1WI), and four combined sequences as well as 3D DTL models. Two integrated models were created using ensemble and stacking algorithms based on optimal radiomics and DTL models. Model performance and clinical benefits were assessed using area under the curve (AUC), decision curve analysis (DCA), net reclassification index (NRI), integrated discrimination index (IDI), and the Delong test for model comparisons. Multiparametric MRI models were superior to single-sequence models for radiomics or DTL models. Ensemble and stacking integrated models displayed excellent performance. The stacking model had the highest average AUC (0.908) and accuracy (0.883) in external validation groups 1 and 2 (AUC = 0.965 and 0.851, respectively) and emerged as the best predictive model for CSI. All models significantly outperformed the radiologist (P < 0.05). In terms of net benefits, all models demonstrated favorable outcomes in DCA, NRI, and IDI, with the stacking model yielding the highest net benefit. Multiparametric MRI-based radiomics combined with 3D DTL can be used to noninvasively predict CSI in EC patients with greater diagnostic accuracy than the radiologist. Stacking integrated models showed significant potential utility in predicting CSI. Which helps to provide new treatment strategy for clinicians to treat early-stage EC patients.

Diagnostic utility of apparent diffusion coefficient in preoperative assessment of endometrial cancer: are we ready for the 2023 FIGO staging?

BackgroundAlthough endometrial cancer (EC) is staged surgically, magnetic resonance imaging (MRI) plays a critical role in assessing and selecting the most appropriate treatment planning. We aimed to assess the diagnostic performance of quantitative analysis of diffusion-weighted imaging (DWI) in preoperative assessment of EC.MethodsProspective analysis was done for sixty-eight patients with pathology-proven endometrial cancer who underwent MRI and DWI. Apparent diffusion coefficient (ADC) values were measured by two independent radiologists and compared with the postoperative pathological results.ResultsThere was excellent inter-observer reliability in measuring ADCmean values. There were statistically significant lower ADCmean values in patients with deep myometrial invasion (MI), cervical stromal invasion (CSI), type II EC, and lympho-vascular space involvement (LVSI) (AUC = 0.717, 0.816, 0.999, and 0.735 respectively) with optimal cut-off values of ≤ 0.84, ≤ 0.84, ≤ 0.78 and ≤ 0.82 mm2/s respectively. Also, there was a statistically significant negative correlation between ADC values and the updated 2023 FIGO stage and tumor grade (strong association), and the 2009 FIGO stage (medium association).ConclusionsThe preoperative ADCmean values of EC were significantly correlated with main prognostic factors including depth of MI, CSI, EC type, grade, nodal involvement, and LVSI.

Endometrial carcinoma with cervical stromal invasion: Three case reports

BACKGROUND Endometrial cancer is a kind of well-known tumors of female genitourinary system. Cervical stromal invasion is an adverse factor for poor prognosis of endometrial cancer. There is still controversy regarding the use of magnetic resonance imaging (MRI) in the diagnosis of cervical stromal invasion of endometrial cancer. The diagnosis of cervical stromal invasion varies significantly between different observers and institutions. We present a limited case series of the particular pattern of endometrial cancer, which infiltrates the cervical stroma and is often overlooked. CASE SUMMARY We present three cases of endometrial carcinoma with cervical stromal invasion with cancer-free uterine cavity. One patient, a reproductive-aged woman, exhibited irregular menstruation and was diagnosed with endometrial polyps by hysteroscopy and segmental curettage. A MRI scan revealed polypoid nodules within the internal cervical orifice. The other two cases were postmenopausal women who presented with abnormal vaginal bleeding. Hysteroscopy and segmental curettage suggested atypical hyperplasia of the endometrium. MRI scans did not detect any malignant signs in the endometrium. In one case, a non-thickened endometrium was observed, while in another, hyperplasia of the endometrium was seen. Notably, none of these patients had malignant tumors identified in the uterine cavity via MRI scans. However, postoperative pathological results following hysterectomy consistently indicated cervical stromal invasion. CONCLUSION Cervical stromal invasion is easily missed if no cancer is found in the uterine body on MRI. Immunohistochemistry of endoscopic curettage specimens should be conducted to avoid underestimation of the disease.

Sensitivity and specificity of Nuclear Magnetic Resonance for the evaluation of myometrial infiltration, cervical stromal invasion and lymph node involvement and their anatopathological correlation in endometrial cancer

Sensitivity and specificity of Nuclear Magnetic Resonance for the evaluation of myometrial infiltration, cervical stromal invasion and lymph node involvement and their anatopathological correlation in endometrial cancer

Assessment of postoperative therapy de-escalation for early-stage, intermediate-risk cervical cancer

ObjectiveThe objective of this study was to assess the oncologic outcome of surgically-treated patients with early-stage, intermediate-risk cervical cancer according to postoperative therapy modality.MethodsThis retrospective cohort study queried the Japanese...

A seed or soil problem in early endometriosis: stromal cell origin drives cellular invasion and coupling over mesothelial cell origin

To study the role of the mesothelial cells in early endometriosis lesion formation by assessing in vitro cell to cell communication and invasion of endometrial cells across a mesothelial cell monolayer, with both cell types derived from both endometriosis and control patients. Laboratory based experimental study SETTING: University hospital and laboratory PATIENT(S): Consenting reproductive aged women who underwent laparoscopy for gynecologic reasons and were confirmed to either have endometriosis with pathology tissue diagnosis (n=8) or no endometriosis (n=8) at the time of surgery INTERVENTION: Primary stromal cells cultured from endometrial pipelle biopsies and primary mesothelial cells cultured from peritoneal explants were utilized in trans-mesothelial invasion assays and gap junction coupling assays. Comparison of potential for lesion formation, using in vitro models, of both primary endometrial and mesothelial cells from endometriosis and control patients, establishing the former as the primary disease driver. When comparing mesothelial cells from control patients to mesothelial cells from endometriosis patients, there was no significant difference in the amount of stromal cell invasion across either barrier. In contrast, when comparing stromal cell origin, the amount of invasion by endometriosis stromal cells was greater than control stromal cells regardless of whether the mesothelial cell monolayer was derived from disease or control patients. Additionally, primary mesothelial cells induced more gap junction coupling, a requirement for invasion, in stromal cells from endometriosis than control patients, again independent of mesothelial origin. The notable exception was mesothelial cells derived from endometriotic lesion affected areas that showed depressed ability to support invasion. While both endometrial and mesothelial cells need to function for establishment of endometriosis lesions, the endometrium seems to be the key player, serving as an ideal target for diagnostic strategies and therapeutic intervention. This notion is consistent with prior studies, however we are the first to directly test both primary mesothelial and endometrial cells from endometriosis and control patients to compare propensities for mesothelial invasion.

Adjuvant Hysterectomy in Patients After Radiation for Locally Advanced Cervical Cancer: A Single-Center Prospective Longitudinal Study.

Residual or recurrent cervical cancer post-CCRT is a challenging clinical issue, even though there has been much effort in recent decades to increase patient survival after radiation. There is a paucity of literature regarding the role of hysterectomy in recurrent/residual disease after radiation in LACC patients. Such a procedure is controversial and not routinely performed because of difficulties in obtaining tumor-free margins and the high rate of associated morbidity. Evaluate outcomes and morbidities in patients who had undergone hysterectomy for residual or recurrent disease after radiation in LACC patients. This is a prospective observational study on radiotherapy-treated LACC patients (IIB-III) with residual disease or recurrent disease who have undergone adjuvant hysterectomy. This study has been conducted at AHPGIC, Cuttack, with a sample size of 30 patients. 18/30 patients underwent extrafascial hysterectomy, and rest 12 patients had radical hysterectomy. No significant difference in complications, achieving tumor free margins or recurrences post adjuvant hysterectomy based on the radicality of surgery was observed. 5 cases of recurrences post-adjuvant hysterectomy were detected. Some of the factors which had significant association with recurrences post adjuvant hysterectomy were non squamous histology, no preoperative brachytherapy, deep stromal invasion and positive surgical margins. Median follow-up time was 14months (12-27months). This study shows that adjuvant hysterectomy is feasible with good outcome and acceptable morbidity after chemoradiotherapy in cervical cancer patients "If selection of patients for adjuvant hysterectomy is appropriate."

Comparison of Interobserver Variability Between Two Grading Systems Used for Urothelial Carcinoma

Background: Inter-observer variability among pathologists' reports has been a significant challenge in the diagnosis of diseases, especially cancers. Designing a grading system with minimal inter-observer variability can help achieve more accurate diagnoses. Objectives: We aimed to determine whether the grading system proposed by Cheng and colleagues (Cheng’s grading system) can improve inter-observer variability among pathologists in grading urothelial cancer, compared with the World Health Organization (WHO) grading system (2004/2016). Methods: Four pathologists examined all slides of bladder biopsy samples diagnosed as urothelial carcinoma, available in the archives of Imam Reza Hospital, Mashhad, Iran, from 2019 to 2022. Each pathologist reported the tumor grade based on both grading systems, independently of previous answers or the reports of their colleagues. Results: Of 132 samples, the majority were from men (84.1%); the mean age of patients was 66.56±11.31 years. For low and high grades of the WHO system and grade II in Cheng’s grading system, κ = 0.602; agreement was lower for grade III (κ = 0.439) and higher for grade IV (κ = 0.690) compared with the WHO grading system. There was significant agreement among the pathologists in all tumor characteristics, with excellent agreement for stromal invasion (κ = 0.790) and muscular invasion (κ = 0.884), fair to good agreement for WHO 2004/2016 grading (κ = 0.602) and Cheng’s grading (κ = 0.574) overall, and poor agreement for tumor heterogeneity (κ = 0.360). Conclusions: Both grading systems demonstrated favorable agreement among pathologists, without significant differences between the two systems. These results confirm the appropriateness of both grading systems.

The Polish Society of Gynecological Oncology Guidelines for the Diagnosis and Treatment of Cervical Cancer (v2024.0).

Background: Recent publications underscore the need for updated recommendations addressing less radical surgery for <2 cm tumors, induction chemotherapy, or immunotherapy for locally advanced stages of cervical cancer, as well as for the systemic therapy for recurrent or metastatic cervical cancer. Aim: To summarize the current evidence for the diagnosis, treatment, and follow-up of cervical cancer and provide evidence-based clinical practice recommendations. Methods: Developed according to AGREE II standards, the guidelines classify scientific evidence based on the Agency for Health Technology Assessment and Tariff System criteria. Recommendations are graded by evidence strength and consensus level from the development group. Key Results: (1) Early-Stage Cancer: Stromal invasion and lymphovascular space involvement (LVSI) from pretreatment biopsy identify candidates for surgery, particularly for simple hysterectomy. (2) Surgical Approach: Minimally invasive surgery is not recommended, except for T1A, LVSI-negative tumors, due to a reduction in life expectancy. (3) Locally Advanced Cancer: concurrent chemoradiation (CCRT) followed by brachytherapy (BRT) is the cornerstone treatment. Low-risk patients (fewer than two metastatic nodes or FIGO IB2-II) may consider induction chemotherapy (ICT) followed by CCRT and BRT after 7 days. High-risk patients (two or more metastatic nodes or FIGO IIIA, IIIB, and IVA) benefit from pembrolizumab with CCRT and maintenance therapy. (4) Metastatic, Persistent, and Recurrent Cancer: A PD-L1 status from pretreatment biopsy identifies candidates for Pembrolizumab with available systemic treatment, while triplet therapy (Atezolizumab/Bevacizumab/chemotherapy) becomes a PD-L1-independent option. Conclusions: These evidence-based guidelines aim to improve clinical outcomes through precise treatment strategies based on individual risk factors, predictors, and disease stages.

Clinicopathologic characteristics and prognostic factors of patients with surgically treated high-grade neuroendocrine carcinoma of the cervix: A multicenter retrospective study.

To evaluate the prognostic factors and survival outcomes of patients with surgically treated high-grade neuroendocrine carcinoma of the cervix (NECC). This multicenter, retrospective study involved 98 cervical cancer patients with stage IA2-IIA2 and IIIC1/2p high-grade NECC. We divided the patients into two groups based on histology: the pure and mixed groups. All clinicopathologic variables were retrospectively evaluated. Cox regression and Kaplan-Meier methods were used for analysis. In our study, 60 patients were in the pure group and 38 patients were in the mixed group. Cox multivariate analysis showed that mixed histology was a protective factor impacting overall survival (OS) (P = 0.026) and progression free survival (PFS) (P = 0.018) in surgically treated high-grade NECC. Conversely, survival outcomes were negatively impacted by ovarian preservation (OS: HR, 20.84; 95% CI: 5.02-86.57, P < 0.001), age >45 years (OS: HR, 4.50; 95% CI: 1.0-18.83, P = 0.039), tumor size >4 cm (OS: HR, 6.23; 95% CI: 2.34-16.61, P < 0.001), parity >3 (OS: HR, 4.50; 95% CI: 1.02-19.91, P = 0.048), and perineural invasion (OS: HR, 5.21; 95% CI: 1.20-22.53, P = 0.027). Kaplan-Meier survival curves revealed notable differences in histologic type (OS: P = 0.045; PFS: P = 0.024), chemotherapy (OS: P = 0.0056; PFS: P = 0.0041), ovarian preservation (OS: P = 0.00031; PFS: P = 0.0023), uterine invasion (OS: P < 0.0001; PFS: P < 0.0001), and depth of stromal invasion (OS: P = 0.043; PFS: P = 0.022). Patients with mixed histologic types who undergo surgery for high-grade NECC have a better prognosis. Meanwhile, ovarian preservation, tumor size >4 cm, parity >3, age >45 years and perineural invasion were poor prognostic predictors. Therefore, patients with high-risk factors should be considered in clinical practice.

METTL14 Promotes Proliferation, Migration, and Invasion in Endometriotic Stromal Cell Growth by Activating the ZEB1/MEK/ERK Pathway.

The aim of this study was to explore the mechanism of methyltransferase-like 14 (METTL14) on human endometriotic stromal cell (ESC; HEM15A) proliferation, migration, and invasion to provide novel therapy for endometriosis (EMs). Normal human endometrial stromal cells (HESCs) and HEM15A cells were selected. Corresponding controlled experiments were performed to analyze whether overexpression of METTL14, N6-methyladenosine (m6A) methylated ZEB1 mRNA, upregulation of ZEB1, and activating the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) can affect the proliferation, migration, and invasion of HEM15A cells. Materials, Setting, and Methods: HEM15A and HESCs were cultured in vitro. HEM15A cells were treated with oe-METTL14 and oe-zinc finger E-box-binding protein 1 (ZEB1) plasmids, 3-deazaadenosine (3-DAA) and the MEK/ERK pathway inhibitor isoprenaline (ISO). After identifying HEM15A and HESCs, METTL14, ZEB1, p-ERK1/2/ERK1/2, and p-MEK/MEK levels, and cell proliferation, migration, and invasion were assessed. The modification sites of ZEB1 and m6A were predicted using SRAMP database, with an m6A modification level assessed by MeRIP. The binding of YT521-B homology domain 2 (YTHDF2) to ZEB1 messenger RNA (mRNA), and ZEB1 stability and mRNA level were tested. Compared with HESCs, METTL14 level in HEM15A was significantly reduced. METTL14 overexpression in HEM15A prominently increased its proliferation, migration, and invasion. METTL14 overexpression notably elevated m6A-methylated ZEB1 mRNA level and reduced the stability and expression of ZEB1 mRNA. Further m6A modification inhibition increased ZEB1 mRNA stability and mRNA and protein levels and decreased ZEB1 m6A modification level. ZEB1 upregulation partially reversed METTL14 overexpression-inhibited HEM15A proliferation, migration, and invasion. METTL14 inhibited the MEK/ERK signaling activation by regulating ZEB1, and the MEK/ERK signaling activation partly averted METTL14-suppressed proliferation, migration, and invasion. The effects of METTL14 on other growth aspects of HEM15A cells and the relation between ZEB1 and m6A require further investigation. METTL14 lowered ZEB1 expression by regulating ZEB1 m6A modification levels, thereby inhibiting the activation of the MEK/ERK pathway and ESC proliferation, migration, and invasion.

Predictive factors for adnexal involvement in endometrial cancer FIGO stage IIIA

ObjectiveUnderstanding ovarian involvement incidence and risk factors in women with endometrial cancer may inform the decision of ovary preservation.MethodsOur retrospective study included all consecutive fully surgically staged patients with endometrial...

Impact of Adenomyosis on In Vitro Fertilization Outcomes in Women Undergoing Donor Oocyte Transfers: A Prospective Observational Study

(Abstracted from Fertil Steril 2024;121(3)) Adenomyosis is a common gynecological condition characterized by the invasion of endometrial glands and stroma from the basal layer of the endometrium into the myometrium. Although adenomyosis is frequently discovered in the diagnostic workup of couples with infertility, it is unclear whether adenomyosis causes infertility.

Treatment Patterns and Surgical Outcomes of Stage IA1 Cervical Carcinoma

OBJECTIVE The primary objective was to determine the 5-year overall survival rate and 5-year disease-free survival rate of patients with CACx 1A1 treated at Chiang Mai University Hospital and the secondary objective was to describe treatment modalities as well as their associated complications. METHODS Patients with stage IA1 cervical cancer diagnosed from January 2001 to June 2018 at Chiang Mai University Hospital were retrospectively reviewed. Inclusion criteria included previously untreated patients diagnosed with stage IA1 cervical cancer (2018 FIGO staging system). Exclusion criteria were patients with recurrent cervical cancer, other gynecologic malignancies, and those in a pregnant state. The analysis included treatment patterns, surgical types, and clinicopathologic variables, i.e., nodal metastasis, parametrial involvement, positive surgical margins, deep stromal invasion (DSI), lymph-vascular space invasion (LVSI), adjuvant treatment, 5-year disease-free survival, and 5-year overall survival. All pathologic slides were reviewed by gynecologic pathologists. The Kruskal-Wallis test, Fisher’s exact test, the Kaplan-Meier method and log-rank test were used for statistical analysis. RESULTS Of the 184 patients included in this study, simple hysterectomy was the most common treatment (57.3%), followed by modified radical hysterectomy (MRH) and radical hysterectomy (RH) (27.6% and 9.7% respectively). Conization and radiation were chosen in a few cases. At the median follow up time of 40.8 months, the 5-year disease free survival rate was 99.1% and the 5-year overall survival rate was 95.0%. Pelvic lymph node dissection was done in 62 cases (33.7%), but only one case (0.54%) had pelvic lymph node metastasis. CONCLUSIONS The surgical and survival outcomes for women with stage IA1 cervical cancer are excellent. They can be effectively treated with less radical interventions such as simple hysterectomy and conization. Lymph node metastasis is rare at this stage (0.54%); therefore, lympha-denectomy may possibly be omitted. KEYWORDS cervical cancer, IA1, treatment outcome

The role of neoadjuvant chemotherapy before radical surgery in stage IB2/IIA2 squamous cell cervical cancers

BackgroundThis study aimed to evaluate the outcomes of patients diagnosed with stage IB2/IIA2 cervical squamous cell carcinoma who underwent neoadjuvant chemotherapy (NACT) prior to radical hysterectomy compared to those who did not receive NACT before surgery.Materials and methodsThis is a multicenter study including data of 6 gynecological oncology departments. The study is approved from one of the institution’s local ethics committee. Patients were stratified into two cohorts based on the receipt of NACT preceding their surgical intervention. Clinico-pathological factors and progression-free survival were analyzed.ResultsTotally 87 patients were included. Lymphovascular space invasion (LVSI) was observed as 40% in the group receiving NACT, while it was 66.1% in the group not receiving NACT (p = 0.036). Deep stromal invasion (> 50%) was 56% in the group receiving NACT and 84.8% in the group not receiving NACT (p = 0.001). In the univariate analysis, application of NACT is statistically significant among the factors that would be associated with disease-free survival. Consequently, a multivariate analysis was conducted for progression-free survival, incorporating factors such as the depth of stromal invasion, the presence of LVSI, and the administration of NACT. Of these, only the administration of NACT emerged as an independent predictor associated with decreased progression-free survival. (RR:5.88; 95% CI: 1.63–21.25; p = 0.07).ConclusionsNACT shouldn’t be used routinely in patients with stage IB2/IIA2 cervical cancer before radical surgery. Presented as oral presentation at National Congress of Gynaecological Oncology & National Congress of Cervical Pathologies and Colposcopy (2022/ TURKEY).