Endometrial Cancer Metastasis Research Articles

Abstract 4126: The inhibitory effect of statins on distant metastasis and recurrence of endometrial cancer

Abstract Endometrial cancer (EC) is the most common gynecologic malignancy. The most common histological type is endometrioid endometrial cancer (EEC). While the majority of patients present with early-stage and low-grade EEC and have an excellent prognosis, a subset develops distant recurrence derived from EEC after initial treatment of the primary. However, the exact mechanism of distant metastasis and recurrence from EEC is still unclear. In addition, the lack of suitable pre-clinical models is a significant barrier to research for distant metastasis and recurrent cancer derived from EEC. Our preclinical EEC model, the ablation of both Mig-6 and Pten in the uterus (Pgrcre/+Mig-6f/fPtenf/f; Mig-6d/dPtend/d), dramatically accelerates the development of EEC compared to single ablation of either gene. The ablation of both Mig-6 and Pten in the uterus (Pgrcre/+Mig-6f/f Ptenf/f; Mig-6d/dPtend/d mice) displayed distant metastases into the ovary, diaphragmatic skeletal muscle, lymph node, and lung. However, the Ptend/d mice exhibited endometrial cancer without distant metastases. After hysterectomy of EEC confined to uterus, Mig-6d/dPtend/d mice exhibited recurrent EEC in abdomen and lung. To identify prognostic factors for distant metastatic and recurrent EEC, we performed transcriptomic analysis in endometrial hyperplasia, a precancerous condition, from Ptend/d and Mig-6d/dPtend/d mice. Our transcriptomic analysis identified that cholesterol biosynthesis was the most significantly activated pathway in Mig-6d/dPtend/d mice compared to Ptend/d mice. Statins, also known as HMG-CoA reductase inhibitors, are the most common cholesterol-lowering drugs. We evaluated the effect of atorvastatin on tumorigenesis and recurrence of EEC. Mig-6d/dPtend/d mice treated with atorvastatin displayed significant reduction of tumor size compared to vehicle treated group. For vehicle-treated group, our pathological analysis revealed EEC outside the uterus, therefore EEC had disseminated to involve the ovary, diaphragmatic skeletal muscle, lymph node, and lung. However, EEC was confined to the uterus in the atorvastatin treated group. Furthermore, atorvastatin treatment reduced the rate of recurrent EEC development. This data demonstrated that atorvastatin has a remarkable inhibitory effect on metastasis and recurrence of EEC in Mig-6d/d Ptend/d mice. Our results suggest that statins suppress development of distant metastasis and recurrence in mouse models of EEC with Pten and Mig-6 deficiency by inhibiting cholesterol biosynthesis. Citation Format: Keun Cheon Kim, Jung Yoon Yoo, Russell R Broaddus, Eunhee M Jeong, Mark I Hunter, Tae Hoon Kim, Jae-Wook Jeong. The inhibitory effect of statins on distant metastasis and recurrence of endometrial cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4126.

Risk factors for pelvic and para-aortic lymph node metastasis in non-endometrioid endometrial cancer

PurposeThe aim of this study was to evaluate the risk factors for pelvic lymph node metastasis (LNM) and para-aortic LNM in non-endometrioid endometrial cancer (non-EEC). MethodsA total of 283 patients with non-EEC hospitalized in the First Affiliated Hospital of Zhengzhou University from January 2012 to December 2020 were included. Various characteristics were retrospectively analyzed in relation to LNM. ResultsUnivariable and multivariable logistic regression analysis revealed cervical stromal invasion (OR = 3.441, 95% CI = 1.558–7.6, p = 0.002), myometrial invasion ≥1/2 (OR = 2.661, 95% CI = 1.327–5.337, p < 0.006), lymphovascular space involvement (LVSI) (OR = 4.118, 95% CI = 1.919–8.837, p < 0.001), positive peritoneal cytology (OR = 2.962, 95% CI = 1.344–6.530, p = 0.007), CA125 (OR = 1.002, 95% CI = 1–1.004, p = 0.026) were the independent risk factors for pelvic LNM. And myometrial invasion ≥1/2 (OR = 5.881, 95% CI = 2.056–16.427, p = 0.001), LVSI (OR = 4.962, 95% CI = 1.933–12.740, p = 0.001), adnexal (OR = 5.921, 95% CI = 2.003–17.502, p = 0.001) were the independent risk factors for para-aortic LNM. With the increase of independent risk factors, the rates of LNM were increased significantly. ConclusionsCervical stromal invasion, myometrial invasion ≥1/2, LVSI, positive peritoneal cytology, and CA125 were risk factors for pelvic LNM. Myometrial invasion ≥1/2, LVSI and involvement of the adnexa were risk factors for para-aortic LNM which could provide a good basis to help predict which non-EEC patients are at higher risk for LNM.

The Predictive Value of Preoperative Inflammatory Markers / Lymphocyte Ratios for Endometrial Cancer; What does the eosinophil to lymphocyte ratio means for survival?

Aim: &#x0D; In various solid tumors, cancer-associated inflammation is associated with adverse long-term outcomes. The purpose of this study was to examine the influence of the preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and other systemic inflammatory markers on lymph node metastasis and 5-year survival in endometrial cancer.&#x0D; Materials and Method: &#x0D; A total of 379 female patients at the Gynecology and Obstetrics Clinic of the University Hospital with a final postoperative pathology of endometrial cancer were included in the 5-year survival study. The preoperative total neutrophil, monocyte, eosinophil, and platelet counts were divided by the lymphocyte count to obtain the NLR, monocyte-to-lymphocyte ratio (MLR), eosinophil-to-lymphocyte ratio (ELR), and PLR values. All patients underwent bilateral pelvic paraaortic lymph node dissection and omentectomy in addition to total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH + BSO). The pathology lab at our university evaluated all cytology and postoperative specimens. The staging system used was the FIGO 2009 surgical staging system.&#x0D; Results: &#x0D; The results of our study showed significant correlations between lymph node metastasis and NLR, eosinophil-to-lymphocyte ratio (ELR), and PLR. Only a significant correlation between ELR and survival was discovered when the relationship with 5-year survival was examined. Aditionally significant correlations existed between NLR and cervical stromal involvement, cytology positivity, and stage.&#x0D; Conclusion: &#x0D; The prognostic factors for lymph node metastasis are NLR, PLR, and ELR. Only ELR is predictive of 5-year survival, but more prospective studies on ELR survival prediction are needed.

Preoperative evaluation and a nomogram prediction model for pelvic lymph node metastasis in endometrial cancer

ObjectiveThe primary objective of this study is to explore the preoperative risk factors of pelvic lymph node metastasis (PLNM) in endometrial cancer patients, and construct a nomogram prediction model. Materials and methodsWe retrospectively collected various preoperative clinical characteristics of patients and analyzed their relationship with PLNM. Logistic regression analysis was used to screen for independent risk factors for PLNM of endometrial cancer. A nomogram prediction model was constructed, the receiver operating characteristic (ROC), calibration curve and decision curve analysis (DCA) were constructed and used to assess discrimination, calibration, and net benefit. ResultsOut of the 276 patients, 74 (26.81%) with postoperative pathological confirmation of PLNM. Multivariate logistic regressive analysis demonstrated that preoperative depth of myometrial invasion (DIM) ≥50% determined by Magnetic Resonance Imaging (MRI) (p = 0.003), carbohydrate antigen 125 (CA125) (p = 0.030), carbohydrate antigen 19–9 (CA 19–9) (p = 0.044), and platelet/lymphocyte ratio (PLR) (p = 0.025) could serve as independent risk factors for PLNM. A risk factors-based nomogram prediction model was constructed, which showed good discrimination (AUC = 0.841, p < 0.001) and good efficacy (C-index = 0.842) and good calibration (mean absolute error = 0.046). DCA showed that the model can provide clinical benefits. ConclusionsPreoperative DIM ≥50% determined by MRI, serum CA 19–9, CA125 and PLR could be utilized to predict PLNM in endometrial cancer patients. This nomogram prediction model can provide preoperative help for evaluation and identification of patients with endometrial cancer, and provide a theoretical basis for clinical intervention.

ACSL1-Mediated Fatty Acid β-Oxidation Enhances Metastasis and Proliferation in Endometrial Cancer.

Gynecological malignancies, such as endometrial cancer (EC) and uterine cancer are prevalent. Increased Acyl-CoA synthetase long-chain family member 1 (ACSL1) activity may contribute to aberrant lipid metabolism, which is a potential factor that contributes to the pathogenesis of endometrial cancer. This study aimed to elucidate the potential molecular mechanisms by which ACSL1 is involved in lipid metabolism in endometrial cancer, providing valuable insights for targeted therapeutic strategies. Xenograft mouse models were used to assess the effect of ACSL1 on the regulation of endometrial cancer progression. ACSL1 protein levels were assessed via immunohistochemistry and immunoblotting analysis. To assess the migratory potential of Ishikawa cells, wound-healing and Transwell invasion assays were performed. Changes in lipids in serum samples from mice with endometrial cancer xenotransplants were examined in an untargeted lipidomic study that combined multivariate statistical methods with liquid chromatography‒mass spectrometry (LC/MS). Patient sample and tissue microarray data suggested that higher ACSL1 expression is strongly associated with the malignant progression of EC. Overexpression of ACSL1 enhances fatty acid β-oxidation and 5'-adenylate triphosphate (ATP) generation in EC cells, promoting cell proliferation and migration. Lipidomic analysis revealed that significant changes were induced by ACSL1, including changes to 28 subclasses of lipids and a total of 24,332 distinct lipids that were detected in both positive and negative ion modes. Moreover, pathway analysis revealed the predominant association of these lipid modifications with the AMPK/CPT1C/ATP pathway and fatty acid β-oxidation. This study indicates that ACSL1 regulates the AMPK/CPT1C/ATP pathway, which induces fatty acid β-oxidation, promotes proliferation and migration, and then leads to the malignant progression of EC.

FKBP38 suppresses endometrial cancer cell proliferation and metastasis by inhibiting the mTOR pathway

Endometrial cancer (EC) is a common gynecological malignancy, and advanced-stage or recurrent EC is associated with a high mortality rate owing to the ineffectiveness of currently available treatments. FK506-binding protein 38 (FKBP38) is a member of the immunophilin family and inhibits melanoma and breast cancer cell metastasis. However, the functions of FKBP38 and its potential mechanism in EC remain unclear. Herein, we analyzed the expression levels of FKBP38 in EC cells and found that the FKBP38 expression was high in Ishikawa cells, and low in AN3CA cells, traditionally considered a low grade and a high grade cell line, respectively, in pathology classification. Moreover, FKBP38 inhibited cell proliferation, migration and invasion in EC cells, FKBP38 knockdown significantly promoted tumor growth of Ishikawa cells in a subcutaneous xenograft model and increased the number of lung metastases of Hec-1-A cells in a metastatic mouse model. Furthermore, FKBP38 suppressed several target proteins of epithelial-to-mesenchymal transition (EMT) and reduced the phosphorylation of ribosomal S6 protein (S6), eukaryotic initiation factor 4E-binding protein 1 (4EBP-1), indicating the potent inhibition of the mammalian target of rapamycin (mTOR) pathway. Meanwhile, the inhibition of mTOR neutralized the elevation of EC cell proliferation, migration and invasion after FKBP38 knockdown. In summary, FKBP38 would exert a tumor-suppressing role by modulating the mTOR pathway. Our results indicate that FKBP38 may be considered as a factor of EC metastasis and a new target for EC therapeutic intervention.

Evaluation of factors influencing lymph node metastasis in endometrial cancers: A retrospective study.

The role of lymphadenectomy in the management of early endometrial cancer remains controversial. The aim of our study was to evaluate risk factors associated with nodal metastases in endometrial cancer and to devise a predictive risk model based on the significant risk factors in predicting node metastasis. A retrospective study was conducted on women diagnosed with uterus-confined endometrial cancer, and who underwent surgical staging with pelvic and/or paraaortic lymphadenectomy from our center during July 1, 2017 to June 30, 2019. Clinical details, Magnetic Resonance imaging (MRI)-detected myometrial invasion, and pre and post-operative histological details of tumor were correlated with pelvic and/or para-aortic lymph node metastasis. Risk factors were assessed using logistic regression model and risk models devised. 128 patients were included in the study. Paraaortic lymphadenectomy was done in 72.7% patients. Nodal metastasis was seen in 14.8% of patients. Logistic regression analyses revealed lymphovascular invasion (P = 0.002), parametrial involvement (P = 0.017) and nonendometrioid histology (P = 0.004) to be significant risk factors. Tumor size >2 cm, grade 3 and deep myometrial invasion had higher risk for nodal metastasis, although non-significant. Risk models were derived with sensitivity of 79-89.5%, specificity of 58.7-69.7%, Negative predictive value (NPV) of 95-97% and accuracy of 63-71%. Lymphovascular invasion, nonendometrioid histology and parametrial involvement are independent predictors of lymph node metastasis in endometrial cancer. Risk models using these risk factors can better predict the risk of nodal metastasis and thus avoid lymph node dissection in low risk patients. Our risk models had reasonably good sensitivity in nodal metastasis prediction and require further validation.

Predictive models for lymph node metastasis in endometrial cancer: A systematic review and bibliometric analysis.

Lymph node metastasis is associated with a poorer prognosis in endometrial cancer. The objective was to synthesize and critically appraise existing predictive models for lymph node metastasis risk stratification in endometrial cancer. This study is a systematic review. We searched the Web of Science for articles reporting models predicting lymph node metastasis in endometrial cancer, with a systematic review and bibliometric analysis conducted based upon which. Risk of bias was assessed by the Prediction model Risk Of BiAS assessment Tool (PROBAST). A total of 64 articles were included in the systematic review, published between 2010 and 2023. The most common articles were "development only." Traditional clinicopathological parameters remained the mainstream in models, for example, serum tumor marker, myometrial invasion and tumor grade. Also, models based upon gene-signatures, radiomics and digital histopathological images exhibited an acceptable self-reported performance. The most frequently validated models were the Mayo criteria, which reached a negative predictive value of 97.1%-98.2%. Substantial variability and inconsistency were observed through PROBAST, indicating significant between-study heterogeneity. A further bibliometric analysis revealed a relatively weak link between authors and organizations on models predicting lymph node metastasis in endometrial cancer. A number of predictive models for lymph node metastasis in endometrial cancer have been developed. Although some exhibited promising performance as they demonstrated adequate to good discrimination, few models can currently be recommended for clinical practice due to lack of independent validation, high risk of bias and low consistency in measured predictors. Collaborations between authors, organizations and countries were weak. Model updating, external validation and collaborative research are urgently needed. None.

Diagnostic value of ICG for sentinel lymph node mapping in patients with stage I endometrial cancer

Background. Lymphatic spread is the main route of metastasis in early stage endometrial cancer. Considering its significance, three risk factors of lymph node metastasis were identified. At a high risk of lymph node metastasis in patients with stage I endometrial cancer, pelvic and lumbar lymph node dissection is recommended. In low-risk patients, lymph node dissection is not performed. Lymph node dissection in medium-risk patients is considered as a staging procedure. However, in patients with aggravating factors that prevent extended hysterectomy, lymph node biopsy with ICG mapping and subsequent microstaging may be an alternative to lymph node dissection. Purpose of the study: to analyze the effectiveness of surgical approaches for staging endometrial cancer at different risk factors for lymphatic metastasis.Material and Methods. The treatment outcomes were retrospectively analyzed in 565 patients with stage I endometrial cancer treated at the gynecological oncology department of Botkin City Clinical Hospital and at the gynecological oncology department of Kaluga Regional Clinical Oncology Center from 2021 to 2023. All women were divided into three groups according to the risk factors of lymph node metastasis. Patients underwent hysterectomy, hysterectomy combined with pelvic or pelvic and lumbar lymphadenectomy, as well as hysterectomy with ICG mapping and sentinel lymph node biopsy.Results. A total of 334 endometrial cancer patients underwent surgery at Botkin City Clinical Hospital. In the medium-risk group patients (n=94), who underwent hysterectomy with pelvic (n=36) and pelvic + lumbar lymphadenectomy (n=31), lymph node metastases were detected in 4 (11.1 %) and 6 (19.4 %) patients, respectively. In the high-risk group (n=50) with similar surgeries, metastatic lymph nodes were identified in 2 (10.5 %, n=19) and 6 (26.1 %, n=23) patients, respectively. At Kaluga Regional Oncology Center, 231 patients underwent hysterectomy with sentinel lymph node biopsy. The low-risk group, the medium-risk group, and the high-risk group showed lymph node metastases in 7 (5.47 %), 6 (10.2 %), and 6 (13.6 %) patients, respectively.Conclusion. In stage I endometrial cancer patients with a low risk of lymph node metastasis, hysterectomy with sentinel lymph node biopsy is recommended. For medium-and high-risk groups, hysterectomy with systemic lymphadenectomy is recommended. If it is not possible to remove the pelvic and lumbar lymph nodes, their biopsy with ICG mapping and microstaging can be recommended. A combination of systemic lymphadenectomy with sentinel lymph node biopsy is a promising technique that could hypothetically demonstrate better results in terms of disease staging.

Incidence, risk factors, and a prognostic nomogram for distant metastasis in endometrial cancer: A SEER-based study.

To evaluate the metastatic pattern, identify the risk factors, and establish a nomogram for predicting prognosis of endometrial cancer (EC) with distant metastasis. A retrospective cohort study of women diagnosed with EC was conducted according to the Surveillance, Epidemiology, and End Results (SEER) database during 2010-2017. Multivariate logistic analysis and Cox analysis were performed to identify the risk factors in promoting distant metastasis and predictors associated with overall survival (OS) in this particular subpopulation. A nomogram was then constructed and validated by the concordance index (C-index), the area under the receiver operating characteristic curve (AUC), calibration plots, and decision curve analysis. A total of 2799 cases of distant metastasis in EC patients were identified, with an overall incidence rate of 3.74% from 2010 to 2017. Black race, unmarried status, non-endometrioid histologic types, and grade IV were significant risk factors for distant metastasis in EC patients. Meanwhile, race, histology, grade, metastasis status, surgery, lymphadenectomy, and chemotherapy were identified as independent prognostic factors for OS. A nomogram to predict 1-, 3-, and 5-year OS was established, and presented favorable accuracy and clinical applicability. Patients were further divided into high- and low-risk groups according to the model. The nomogram was developed as a highly accurate, individualized tool to better predict the prognosis of EC patients with distant metastasis, which would help clinicians to identify high-risk patients, and adjust and tailor their treatment strategies.

Endometrial Cancer Stem Cells Related Signaling Pathways

Abstract: Endometrial cancer is gynecologic cancer that occurs in the uterus. Endometrial cancer stem cells (ECSC) are a small population of cancer cells that represent a crucial role in the metastasis of endometrial cancer cells to other organs in the body. ECSC can proliferate and give rise to mature cancer cells, which are found to participate in the aggressiveness of metastatic lesions. Therefore, targeting ECSC can be a valuable strategy for drug development against the metastasis of endometrial cancer. Previous studies have demonstrated that several signaling pathways, including Wnt, mTOR, EGFR, NOTCH, STAT3, VEGF, and SHH show modest effects and regulate the growth, epithelial-to-mesenchymal transition (EMT), and tumorigenesis of ECSC. Non-coding RNAs (ncRNAs) also play an important role in ECSC self-renewal, progression, and drug resistance. Hence, targeting these pathways might be a novel therapeutic approach for endometrial cancer diagnosis and therapy. This mini-review aims to characterize the main signaling pathways involved in the stimulation of ECSCs proliferation and tumorigenesis.

Endometrial cancer (EC) derived G3BP1 overexpression and mutant promote EC tumorigenesis and metastasis via SPOP/ERα axis

BackgroundRas-GTPase-activating protein binding protein 1 (G3BP1) is an oncogenic factor, which highly expressed in a variety of cancers. In recent years, G3BP1 has been reported to promote the development of prostate cancer by inhibiting the degradation of AR through inhibiting SPOP. However, whether G3BP1 contributes in a similar manner to the abnormal accumulation of ERα, which is also an important target for hormone therapy, remains unknown. This article addresses this issue and explores potential mechanisms.MethodsBioinformatics tools were used for G3BP1 expression analysis, survival analysis, and clinical association analysis. Immunohistochemical staining was used to examine the correlation between G3BP1 and ERα in EC patients. In addition, western blot and co-immunoprecipitation were used to detect the half-life of G3BP1 and mutant, and the effect of G3BP1 and mutant on the ubiquitination and degradation of ERα mediated by SPOP. Then, the oncogenic functions of G3BP1 dependent on the SPOP/ERα axis were determined by CCK8 cell proliferation assay, colony formation assay and cell migration assay. Finally, we established the EC cells treated or untreated with fulvestrant, exploring the possibility of fulvestrant combined with the reduction of G3BP1 to improve the efficacy of fulvestrant.ResultsG3BP1 is abnormally high expressed and characterized by high-frequency mutation in EC. In addition, there is a positive correlation between G3BP1 protein and ERα protein. Mechanistically, both G3BP1 and mutant, the latter is displaying the longer half-life, competitively bind SPOP with ERα, thereby inhibiting SPOP-mediated ubiquitination and degradation of ERα. Functionally, G3BP1 and mutant promote the proliferation and migration of EC cells by regulating the G3BP1/SPOP/ERα axis. However, fulvestrant can reverse the cancer-promoting effects of G3BP1 and mutant.ConclusionsG3BP1 and its mutant positively regulate ERα signaling pathway by inhibiting SPOP-mediated ubiquitination and degradation of ERα, indicating the promising effect of fulvestrant on the suppression the occurrence and development of EC with high expressed G3BP1 and G3BP1 mutants.7zf14ZtBi1KWa6qjVt88ZxVideo

Use of clinical variables for preoperative prediction of lymph node metastasis in endometrial cancer.

Endometrial cancer is the most common gynaecological cancer, and most patients are identified during early disease stages. Noninvasive evaluation of lymph node metastasis likely will improve the quality of clinical treatment, for example, by omitting unnecessary lymphadenectomy. The study population comprised 611 patients with endometrial cancer who underwent lymphadenectomy at four types of institutions, comprising seven hospitals in total. We systematically assessed the association of 18 preoperative clinical variables with postoperative lymph node metastasis. We then constructed statistical models for preoperative lymph node metastasis prediction and assessed their performance with a previously proposed system, in which the score was determined by counting the number of high-risk variables among the four predefined ones. Of the preoperative 18 variables evaluated, 10 were significantly associated with postoperative lymph node metastasis. A logistic regression model achieved an area under the curve of 0.85 in predicting lymph node metastasis; this value is significantly higher than that from the previous system (area under the curve, 0.74). When we set the false-negative rate to ~1%, the new predictive model increased the rate of true negatives to 21%, compared with 6.8% from the previous one. We also provide a spreadsheet-based tool for further evaluation of its ability to predict lymph node metastasis in endometrial cancer. Our new lymph node metastasis prediction method, which was based solely on preoperative clinical variables, performed significantly better than the previous method. Although additional evaluation is necessary for its clinical use, our noninvasive system may help improve the clinical treatment of endometrial cancer, complementing minimally invasive sentinel lymph node biopsy.

Clinical Implication of PD-L1 Expression in Patients with Endometrial Cancer.

This study investigated PD-L1 expression in endometrial cancer, its links with prognostic factors, and survival outcomes in 232 patients. Of these, 73 (31.5%) had PD-L1-positive tumors and 159 (68.5%) had PD-L1-negative tumors. PD-L1 expression significantly correlated with adverse prognostic factors. The PD-L1-positive group had higher rates of high-grade tumors (37.0% vs. 19.1%, p = 0.004), deep myometrial invasion (35.6% vs. 24.4%, p = 0.004), lymphovascular space invasion (LVSI) (39.7% vs. 25.6%, p = 0.023), and lymph node metastasis (7.2% vs. 17.1%, p = 0.024) than the PD-L1-negative group. While 5-year progression-free survival (PFS) favored the PD-L1-negative group (94.1% vs. 86.3%), this difference lacked statistical significance (p = 0.139). No significant variations emerged in overall survival (OS) (p = 0.596) or recurrence rates between the groups. Although outcomes lack statistical significance, they suggest a plausible link between PD-L1 and established adverse prognostic factors, such as histological grade, myometrial invasion depth, LVSI, and lymph node metastasis in endometrial cancer. These insights hint at PD-L1's potential as an informal prognostic indicator, potentially aiding in endometrial cancer patient management.

Clinical value of hemoglobin, albumin, lymphocyte, and platelet indexes in predicting lymph node metastasis and recurrence of endometrial cancer: a retrospective study.

To study the clinical importance of hemoglobin, albumin, lymphocyte, and platelet (HALP) indexes in predicting lymph node metastasis and recurrence of endometrial cancer. From July 2016 to July 2020, 158 patients suffering from endometrial cancer who visited the gynecology department of General Hospital of Ningxia Medical University from were collected. Employing the X-Tiles program, the ideal HALP cut-off value was established, and the patients were separated into low and high HALP groups. Univariate and multivariate analysis were used to determine the relationship between HALP score and lymph node metastasis and recurrence of endometrial cancer. The optimal cut-off value of HALP score was established to be 22.2 using X-Tiles software, and the patients were separated into high HALP group (HALP score > 22.2, with 43 cases) and low HALP group (HALP score ≤ 22.2, 115 cases). Endometrial cancer patients' HALP scores were strongly connected with differentiation, the degree of myometrial invasion, and lymph node metastasis (P < 0.05), although not with age, menopausal status, or stage (P > 0.05). Multivariate logistic regression analysis revealed that the HALP score (OR = 2.087) was the influencing factor for lymph node metastasis (P < 0.05). The ROC curve suggested that the AUC of HALP score in predicting lymph node metastasis was 0.871, which had high diagnostic value. When compared to patients without recurrence, HALP scores of patients with recurrence were considerably lower (P < 0.05). Multivariate logistic regression analysis showed that HALP score (OR = 2.216) was the influencing factor for the occurrence of lymph node metastasis (P < 0.05). The ROC curve suggested that the AUC of HALP score in predicting relapse was 0.855, with high diagnostic value. The HALP score shows good predictive performance in predicting lymph node metastasis and recurrence of endometrial cancer, and has high clinical value, which helps in improving the accuracy and effectiveness of clinical diagnosis and prognosis research.

Adrenal gland metastasis of endometrial cancer: A case report

Adrenal gland metastasis of endometrial cancer: A case report

CircCCL22 Regulates CDC25A via Sponging miR-543 and Promotes Proliferation and Metastasis in Endometrial Cancer.

Endometrial cancer (EC) is the most common gynecological tumor. Circular RNAs are a novel type of non-coding RNA that have important regulatory functions, particularly in the pathogenic progression of cancer. In this study, we investigated the function of circCCL22, and elucidated its molecular mechanism in EC progresssion. The expression of circCCL22, miR-543 and CDC25A in EC tissues and cells were determined by qRT-PCR and western blot. Cell counting kit-8, 5-ethynyl-2'-deoxyuridine, wound healing and transwell assays were executed to assess the cell viability, proliferation, migration and invasion. Dual-luciferase report assay was utilized to investigate the interaction of miR-543 with circCCL22 and CDC25A. The role of circCCL22 in EC in vivo was investigated by xenograft assay. CircCCL22 was notably upregulated in EC tissues and cells. Functionally, circCCL22 knockdown suppressed EC cell proliferation, migration and invasion in vitro, and inhibited tumor growth in vivo. Mechanistically, circCCL22 acted as "miR-543 sponges" to regulate its targeted gene CDC25A expression in EC cells. The inhibiting effect induced by circCCL22 knockdown on EC cell proliferation, migration and invasion was greatly reversed by miR-543 inhibition or CDC25A overexpression. Our results revealed that circCCL22 regulated EC progression through targeting miR-543/CDC25A axis, and it could be a novel therapeutic target of EC.

Validation of Sentinel Lymph Node Biopsy in Robotic Endometrial Cancer Staging Surgery: Results From a High-Volume Center in India

PURPOSE Lymph node involvement is one of the most important factors influencing recurrence and survival in patients with endometrial cancer (EC). However, the therapeutic role of lymphadenectomy in early-stage disease has been called into question. Sentinel lymph node (SLN) mapping may be an acceptable alternative to omitting lymphadenectomy or performing a complete lymphadenectomy in patients with EC. To validate SLN biopsy (SLNB) using indocyanine green (ICG) dye and near-infrared imaging in the background of comprehensive lymphadenectomy in patients with EC undergoing robotic staging surgery at Tata Medical Center. METHODS This was a single-center, prospective observational study involving patients with EC undergoing robotic staging. Patients received a standardized cervical injection of ICG at the 3- and 9-o'clock positions, with the dye reinjected if mapping failed. Depending on preoperative histology and radiological staging, patients had SLNB or comprehensive systematic lymphadenectomy in addition to SLNB. RESULTS The study included 105 female patients, of whom 71 underwent SLN and full lymphadenectomy and 34 underwent only SLN. There was bilateral mapping in 92 (87.61%) patients, with no mapping in one patient. In 18 patients, ICG dye was reinjected. With the exception of one, the rest had successful mapping after reinjection. The sensitivity of the SLN-ICG algorithm was 92.3%, and the negative predictive value was 98.3%. Ultrastaging necessitated upstaging in 8.57% of patients. CONCLUSION With a very high negative predictive value, SLN mapping with ICG dye has a high degree of diagnostic accuracy in detecting lymph node metastases in EC.

The oncologic outcomes of endometrial cancer metastasizing to the adrenal gland and kidney: from case to analysis.

To evaluate the oncologic outcomes of endometrial cancer metastasis to the adrenal gland and kidney, based on a case study and review of the literature. A systematic review of the medical literature was performed to identify articles about metastatic endometrial cancer to the adrenal gland and kidney from 1975 until 2021. A 55-year-old female patient was admitted to our center. On pelvic examination, a mass protruding out of the cervix was observed, which was shown to be endometrioid carcinoma on biopsy. Disease stage was IVB, based on radiological and pathological results and the International Federation of Gynecology and Obstetrics 2018 staging. Neo-adjuvant chemotherapy was given. After therapy, the patient underwent type 2 hysterectomy, bilateral salpingo-oophorectomy, total omentectomy and lymph node dissection. Left nephrectomy, left adrenalectomy and left hemicolectomy were also performed because the conglomerate tumor invaded the left kidney, left adrenal gland, and left colon mesentery. Pathological findings were consistent with metastasis of endometrioid carcinoma in the left adrenal gland, left kidney parenchyma and hilum. Metastasis of endometrial cancer to the adrenal gland and kidney is extremely rare and metastasis to the kidney has been reported in only two previous cases. When there is an intraperitoneal spread of endometrial cancer, as well as ovarian cancer, cytoreductive surgery without leaving a residual tumor should be undertaken andshould include adrenalectomy and nephrectomy, if necessary.

Fumarate hydratase functions as a tumor suppressor in endometrial cancer by inactivating EGFR signaling.

Fumarase hydratase (FH) is an enzyme that catalyzes the reversible hydration and dehydration of fumarate to malate in the tricarboxylic acid cycle. The present study addressed the role of FH in endometrial cancer and clinically observed that the expression of FH was significantly lower in endometrial cancer tissues compared with normal endometrial tissues and, furthermore, that the decreased FH expression in endometrial cancer tissues was significantly associated with increased tumor size and lymph node metastasis. Further analysis in invitro study showed that cell proliferation, migration and invasion abilities were increased when the expression of FH in the endometrial cancer cells was knocked down, but, by contrast, overexpression of FH in endometrial cancer cells decreased cell proliferative, migratory and invasive abilities. Mechanistic studies showed that the expression of vimentin and twist, being two well-studied mesenchymal markers in endometrial cancer cells, were upregulated in fumarate hydratase-knockdowned cells. In addition, phosphokinase array analysis demonstrated that the expression of phospho-EGFR (Y1086), which promotes carcinogenesis in cancers, was increased in endometrial cancer cells when FH was knocked down. In conclusion, the present study suggested that FH is a tumor suppressor and inhibits endometrial cancer cell proliferation and metastasis by inactivation of EGFR. Further studies are required to clarify its role as a prognostic biomarker and therapeutic target for endometrial cancer.