Expression In Endometrial Carcinoma Research Articles

Tumoral programmed cell death 1 (PD1) expression in endometrial carcinoma is a prognostic marker for patient outcome

ObjectiveImmune checkpoint inhibitors have recently demonstrated benefit in patients with advanced and recurrent endometrial carcinoma. This retrospective study investigated immune checkpoint molecules in endometrial carcinoma as they pertain to the...

Immunohistochemical expression of B-cell lymphoma 2 gene -Bcl-2 in endometrial carcinoma

Background and objectives: Apoptosis, a process of cell death, is inhibited by the B-cell lymphoma 2 protein, leading to the prolonged survival of cells. Participation of Bcl-2 in starting and advancement of endometrial carcinoma remains inconclusive, with varying results observed. The aims of this study were to assess the frequency of B-cell lymphoma 2 expression in endometrial carcinoma, and to investigate the connection between B-cell lymphoma 2 expression with some clinicopathological parameters. Methods: A retrospective study was carried out for seventy-eight formalin fixed paraffin embedded blocks of total abdominal hysterectomy specimens diagnosed as endometrial carcinoma, which were randomly obtained from a private laboratory and Rizgary teaching hospital laboratory in Erbil city during June 2021-June 2022. In this study, endometrial carcinoma cases were subjected to the utilization of B-cell lymphoma 2 gene, which is a Mouse monoclonal antibody, and its expression was evaluated. Results: The expression of Bcl-2 was observed in 61.5% of the studied cases. The majority (93.6%) of EC cases were of low grade, although Bcl-2 expression was observed at a greater frequency (64.4%) in low-grade endometrial carcinoma, but there was no significant association. Additionally, no statistically significant correlation was found between B-cell lymphoma 2 gene expression and other clinicopathological parameters like, age, myometrial invasion, lympho-vascular invasion, lymph node status and tumor stage. Conclusion: Bcl-2 was expressed in 61.5% of the studied cases with no significant association with any of the variables, additional research is necessary to assess the expression of B-cell lymphoma 2 gene in relation to endometrial carcinoma invasion and metastasis.

Prognostic Significance of L1CAM Expression in Endometrial Carcinoma

Prognostic Significance of L1CAM Expression in Endometrial Carcinoma

R1 Title: Prognostic Significance of L1CAM Expression in Endometrial Carcinoma

R1 Title: Prognostic Significance of L1CAM Expression in Endometrial Carcinoma

Upregulation of sperm-associated antigen 5 expression in endometrial carcinoma was associated with poor prognosis and immune dysregulation, and promoted cell migration and invasion

Sperm-associated antigen 5 (SPAG5) regulates cancer cell invasion and is involved in the progression of many cancers. However, the role of SPAG5 in endometrial carcinoma (EC) is still unknown. The purpose of this study was to explore the role of SPAG5 in EC and its potential molecular mechanism. The UALCAN tool and cBioPortal were used to analyze the expression and alterations of SPAG5 in EC, respectively. OncoLnc was used for survival analysis. We analyzed the effects of SPAG5 on immune cell infiltration and the expression levels of immune checkpoints. We also overexpressed and knocked down SPAG5 in EC cells to explore the effect of SPAG5 regulation on migration, invasion, apoptosis, and the cell cycle of EC cells. We found that SPAG5 was overexpressed and the SPAG5 gene was often mutated in EC. High SPAG5 expression was significantly associated with poor overall survival in patients with EC. SPAG5 also affected the level of immune cell infiltration in the TIME and the expression of immune checkpoints lymphocyte activating 3 (LAG3) and T cell immunoreceptor with Ig and ITIM domains (TIGIT) in patients with EC. It may also be involved in the immunotherapy response in these patients. In vitro experiments showed that SPAG5 promotes cancer cell migration and invasion. In conclusion, this study lays the foundation for further understanding the molecular mechanisms of EC involving SPAG5 and contributes to diagnosing and managing this disease.

Assessment of Galectins -1, -2, -3, and -8 Expression in Endometrial Carcinoma and Its Clinical Implications

Assessment of Galectins -1, -2, -3, and -8 Expression in Endometrial Carcinoma and Its Clinical Implications

PD-L1 Immunohistochemical Expression in Endometrial Carcinoma: Egyptian Cross-Sectional Study.

Endometrial carcinoma (EC) is the most common cancer of the female genital tract. According to the recently evolved strategies of cancer immunotherapy, immune checkpoints inhibitors are one of the most crucial strategies. Programmed Death Ligand 1 (PD-L1) is an important immune checkpoint regulator. PD-L1 antibodies have shown efficacy in clinical trials of some malignancies. Some of these antibodies have been approved for clinical usage by the Food and Drug Administration (FDA). This retrospective study included a total of 100 ECs, collected from archived, formalin-fixed, paraffin-embedded tissue blocks of hysterectomy specimens of Egyptian females. The samples were immunohistochemically analyzed for PD-L1 expression (in both tumor cells; TCs and tumor infiltrating leucocytes; TILs) by a semiquantitative score (0 to 4), with cutoff points of (0: <1% of the cells, 1: 1% to 4%, 2: 5% to 9%, 3: 10% to 49%, and 4: ≥ 50%). Membranous staining only was considered positive. PD-L1 was highly expressed in ECs (67% TCs+ and 61% TILs+), with statistically significant relationships with age, lympho-vascular space invasion (LVSI) and TILs score (P = 0.006, 0.016 and <0.005 respectively). However, no statistically significant relationships were detected between PD-L1 expression and the following parameters: histological type, histological grade, pathological stage (pT) or FIGO stage, myometrial, cervical, adnexal/serosal, parametrial involvements and nodal metastasis, as well as ESMO risk stratification system. Moreover, statistically significant relationships were achieved when correlating TILs score with tumor grade and LVSI (P = 0.034 and 0.012 respectively). Also, comparing endometrial hyperplasia (EH) PD-L1 and TCs PDL1 median scores achieved statistically significant relationship (P = 0.001). Our results concluded that PD-L1 expression was greater in both TCs and TILs in a subgroup of patients that have advanced age, LVSI and are TILs-rich, identifying them as potential candidates for anti-PD-1/PD-L1 immunotherapy.

Clinicopathological Significance of Nucleosome Remodeling and Deacetylase Complex Expression in Endometrial Carcinoma.

Only a few studies have examined the expression of nucleosome remodeling and deacetylase complex in endometrial carcinoma (EC). The aim of this study was to analyze the expressions of histone deacetylase (HDAC1), HDAC2, and chromodomain helicase DNA-binding protein 4 (CHD4) in EC. Sixty cases of EC were categorized into two clusters based on the expression levels of the three proteins. Cluster 1 (C1) exhibited elevated expressions of HDAC2 and CHD4 compared with cluster 2 (C2). Notably, 75% of cases in C2 represented non-aggressive histological types, whereas 37.5% of cases in C1 manifested aggressive types. C2 exclusively comprised pathological tumor stage 1 (pT1) tumors, whereas C1 included pT2 and pT3 tumors. In C1, 25% of cases displayed aberrant p53 expression, contrasting with the absence of such expression in C2. Furthermore, only one patient in C2 experienced disease recurrence, whereas 20.8% of patients in C1 developed recurrent tumors. High HDAC2 and CHD4 expression may be associated with adverse clinicopathological characteristics in EC. Further studies are needed to validate these results.

E-Cadherin Expression in Endometrial Carcinoma

E-Cadherin Expression in Endometrial Carcinoma

Value of Multimodal Diffusion-weighted Imaging in Preoperative Evaluation of Ki-67 Expression in Endometrial Carcinoma.

To investigate the value of multimodal diffusion weighted imaging (DWI) in preoperative evaluation of Ki-67 expression of endometrial carcinoma (EC). Patients who had undergone pelvic DWI, intravoxel incoherent motion (IVIM), and diffusion kurtosis imaging (DKI) sequence MRI scan before surgery were retrospectively enrolled. Single index model, double index model, and DKI were used for post-processing of the DWI data, and the apparent diffusion coefficient (ADC), real diffusion coefficient (D), pseudo diffusion coefficient (D*), perfusion fraction (f), non-Gaussian mean diffusion kurtosis (MK), mean diffusion coefficient (MD) and anisotropy fraction (FA) were calculated and compared between the Ki-67 high (≥50%) and low (<50%) expression groups. Forty-two patients with a median age of 56 (range 37 - 75) years were enrolled, including 15 patients with a high Ki-67 (≥50%) expression and 27 with a low Ki-67 (<50%) expression. The MK (0.91 ± 0.12 vs. 0.76 ± 0.12) was significantly (P<0.05) higher while MD (0.99 ± 0.17 vs. 1.16 ± 0.22), D (0.55 ± 0.06 vs. 0.62 ± 0.08), and f (0.21 vs. 0.28) were significantly (P<0.05) lower in the high than in the low expression group. The combined model of MK, MD, D, and f-values had the largest area under the curve (AUC) value of 0.869 (95% CI: 0.764-0.974), sensitivity 0.733 and specificity 0.852, followed by the MK value with an AUC value 0.827 (95% CI: 0.700-0.954), sensitivity 0.733 and specificity 0.815. IVIM and DKI have certain diagnostic values for preoperative evaluation of the EC Ki-67 expression, and the combined model has the highest diagnostic efficiency.

Expression of DKK1 in Endometrial Endometrioid Carcinoma and Its Correlation with Wnt/β-catenin Signalling Pathway.

Endometrial cancer is the most prevalent form of cancer affecting female reproductive organs. The most common histologic type, endometrioid carcinoma, accounts for 75-80% of all endometrial cancer cases. Studies on DKK1 expression profiles and their inhibitory role in the Wnt signalling pathway in the genesis and development of endometrial carcinoma are scarce. This study aimed to investigate DKK1 expression in endometrial carcinoma and its correlation with the Wnt/β-catenin pathway. A total of 160 formalin-fixed paraffin-embedded samples were included in this study (50 cases of endometrial atypical hyperplasia, 50 cases of endometrioid endometrial carcinoma, 30 cases of proliferative endometrium and 30 cases of secretory endometrium). The expression patterns of DKK1, E-cadherin, β-catenin and c-Myc in endometrial atypical hyperplasia and carcinoma were investigated and compared with that of proliferative and secretory endometrium. Immunohistochemistry and analysis were performed from July 2018 to June 2020. A decreasing pattern of immunopositivity for DKK1, E-cadherin and β-catenin from proliferative/secretory endometrium to endometrial atypical hyperplasia and endometrioid carcinoma was found. Increasing c-Myc immunopositivity was noted from proliferative/secretory endometrium to endometrial atypical hyperplasia and endometrioid carcinoma. Moreover, decreasing DKK1 immunopositivity was well correlated with E-cadherin, β-catenin and c-Myc immunopositivity. Decreasing DKK1 positivity from benign endometrium to endometrioid carcinoma suggests a negative regulatory function of DKK1 in endometrioid carcinoma. DKK1 is downregulated in the Wnt signalling pathway in endometrioid endometrial carcinoma. Therefore, DKK1 is promising as a biomarker for screening endometrioid carcinoma. Future studies should examine the reactivation of the DKK1 gene, which may be a valuable strategy for antagonising the Wnt signalling pathway.

Androgen Receptor Expression in Endometrial Carcinoma and its Correlation with Clinicopathological Features-An Experience at a Tertiary Care Hospital in North India

Androgen Receptor Expression in Endometrial Carcinoma and its Correlation with Clinicopathological Features-An Experience at a Tertiary Care Hospital in North India

Significance analysis of PAX8 expression in endometrial carcinoma.

To analyze the expression and prognostic value of paired-box 8 (PAX8) expression in uterine corpus endometrial carcinoma (UCEC) by bioinformatics. The expression of PAX8 gene in UCEC was analyzed by R language and immunohistochemistry. The correlation between PAX8 expression and clinicopathological features was analyzed by R language. The prognostic factors was analyzed by univariate/multivariate regression. The survival curve of patients was analyzed by Kaplan–Meier Plotter (K–M Plotter). The diagnostic value of PAX8 in UCEC was analyzed by receiver operating characteristic curve, and the relationship between PAX8 expression and methylation was analyzed by Ualcan. The relationship between methylation and prognosis was analyzed by MethSurv database. The expression of PAX8 in cancer tissues was significantly higher than that in normal tissues. The expression of PAX8 was related to clinical stage, age, histological type, histologic grade, tumor invasion and disease-specific survival event. Univariate/multivariate regression analysis showed that clinical stage, tumor invasion, and PAX8 expression were the influence factors of overall survival (OS), while histologic grade and PAX8 expression were the influence factors of disease-specific survival, and patients with low expression had a longer OS. The area under the curve of receiver operating characteristic curve was 0.81 for PAX8 diagnosis of UCEC. PAX8 was hypomethylated in cancer tissue, and patients with hypermethylated PAX8 had a longer OS. The high expression of PAX8 induced by hypomethylation may play an important role in the occurrence and prognosis of UCEC.

CYLD expression in endometrial carcinoma and correlation with clinicohistopathological parameters

ObjectiveEndometrial cancer is a threat to women health worldwide. Cylindromatosis (CYLD) enzyme is a tumour suppressor, considered an effective prognostic marker in various malignancies, but its role in endometrial carcinoma is not fully elucidated. Here, we sought to estimate the prognostic value of CYLD expression in endometrial carcinoma. Materials and methodsCYLD levels were immunohistochemically evaluated in 65 patients with endometrial carcinoma and inferential statistics were applied. ResultsLow or negative CYLD expression significantly correlates with older ages, non-endometrioid and invasive carcinomas, tumours with moderate or poor differentiation and advanced stages. Moreover, non-endometrioid and invasive carcinomas are independent risk factors for weaker CYLD expression. Kaplan–Meier analysis illustrated that negative or low CYLD expression is statistically significantly associated with increased death risk, compared to moderate or high expression. ConclusionThis study demonstrates for the first time a clear correlation between CYLD expression and clinicohistopathological parameters of endometrial carcinoma patients, suggesting its use as a potential prognostic/predictive marker for Endometrial Carcinoma.

PRAME Expression in Endometrioid and Serous Endometrial Carcinoma: A Potential Immunotherapeutic Target and Possible Diagnostic Pitfall.

Preferentially expressed antigen in melanoma (PRAME) is a cancer testes antigen initially employed as a diagnostic marker for melanoma. Although negative in most normal tissues, its expression has been reported in benign endometrial glands. Additionally, PRAME expression has been identified in a growing list of solid and hematologic malignancies and is of interest as a predictive biomarker, as cancer vaccination strategies and adoptive T-cell transfer targeting this molecule are under clinical investigation; additionally, PRAME may identify candidates for retinoid therapy. However, expression of PRAME has not been well-studied in endometrial cancers. We herein evaluate PRAME expression in endometrial carcinomas to better characterize its limitations as a diagnostic melanoma marker as well as its potential as a predictive biomarker in endometrial carcinomas. PRAME expression was evaluated in 256 endometrioid (n=235) and serous (n=21) endometrial carcinomas via tissue microarray. In all, 89% (227/256) demonstrated some degree of nuclear PRAME expression, including 88% (207/235) of endometrioid carcinomas and 95% (20/21) of serous carcinomas. Diffuse (>50%) expression was observed in 70% (179/256) of all cases, including 69% (163/235) of endometrioid carcinomas and 76% (16/21) of serous carcinomas. There was no association between degree of expression and grade, mismatch repair protein status, or stage. The widespread expression of PRAME in endometrial carcinomas suggests this marker should not be interpreted as specific for melanoma in this context. However PRAME may have utility as a predictive biomarker in endometrial cancer, and expansion of testing of PRAME-based therapies to endometrioid and serous endometrial carcinomas may lead to new therapeutic options for these endometrial cancer subtypes.

Metformin Regulates TET2 Expression to Inhibit Endometrial Carcinoma Proliferation: A New Mechanism.

ObjectivesTo investigate the relationship between TET2 expression and endometrial cancer’s clinicopathological features and prognosis, and the effect of metformin on TET2 and 5hmC levels in endometrial cancer cells.MethodsThe clinical significance of TET2 expression in endometrial carcinoma was analyzed from TCGA public database. Eighty-eight patients with endometrial cancer and 20 patients with normal proliferative endometrium were enrolled in this study. TET2 and 5hmC were respectively detected by Immunohistochemistry and ELISA in endometrial tissues. Kaplan-Meier and Cox proportional hazard regression models were used to analyze relationships between TET2 and 5hmC and the overall survival of EC patients. Endometrial cell proliferation was assessed after TET2 gene knockdown. Western blotting and real-time PCR were used to detect the effect of metformin on TET2 expression and to explore whether AMPK is involved in metformin-mediated TET2 regulation.ResultsThe clinical significance of expression of TET2 in endometrial cancer from TCGA public database confirmed that TET2 expression was significantly down-regulated in cancer samples and TET2 expression was also significantly different among different histopathological samples and TET2 is down-regulated in advanced, high-grade, and relapsed endometrial carcinoma tissues(P<0.05). Immunohistochemical analysis showed that TET2 and 5hmC levels were significantly lower in endometrial adenocarcinoma(P<0.05). TET2 expression was correlated with the degree of EC differentiation (P < 0.05). 5hmC levels were associated with clinical stage, differentiation, the depth of myometrial invasion, and lymph node metastasis (P < 0.05). The mean survival time of patients with negative staining for TET2 and 5hmC was shorter than that of patients with positive staining for both markers (P<0.05). Multivariate Cox regression analysis showed that TET2 expression was an independent risk factor for prognosis in patients with endometrial adenocarcinoma (HR = 14.520, 95% CI was 1.From 060 to 198.843, P = 0.045). siRNA-mediated TET2 knockdown increased the proliferation of EC cells. Metformin increased the levels of TET2 and 5hmC in EC cells. AMPK was involved in the regulation of TET2 by metformin.ConclusionsTET2 may play an important role in EC development and may be a prognostic marker. Moreover, TET2 may be involved in a novel mechanism by which metformin inhibits EC cell proliferation.

Significance of CD47 expression in endometrial carcinoma.

CD47 is a membrane protein that belongs to the immunoglobulin superfamily and regulates macrophage phagocytosis negatively. As CD47 expression at the cancer cell membrane would inhibit the phagocytic activity of immune cells, it is connected to an unfavorable prognosis in leukemia and malignancies of various solid organs. Materials and. In this study, retrospectively evaluated 72 patients who had been diagnosed with endometrial carcinoma at Pathology Department and had undergone total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH + BSO) and/or lymphadenectomy. CD47 expression was evaluated in tumorous and nontumor areas in all patients considering cytoplasmic and membranous brown staining in cells. The proportion of expression was evaluated as well as the intensity and an "h score" was obtained. This score was compared with known prognostic parameters. CD47 expressions showed a statistically significant correlation with tumor grade (P < 0.05); however, no significant relationship was observed with myometrial invasion depth and lymph vascular invasion status (P = 0.923 and P = 0.754, respectively). As with other tumors, anti-CD47 antibody may be an alternative treatment option in patients with high-grade endometrial carcinoma.

High-mobility group AT-hook 2 expression in serous and endometrioid endometrial carcinomas

Background Subtyping of endometrial carcinoma, mainly high-grade cases, is a major pathological dilemma. Several biomarkers have been evaluated for differentiation between serous endometrial carcinoma (SEC) and endometrioid endometrial carcinoma (EEC), with variable sensitivity and specificity. Aim To evaluate the diagnostic role of high-mobility group AT-hook 2 (HMGA-2) in differentiation between SEC and EEC, compared with p16 and progesterone receptor (PR), and to evaluate HMGA-2 expression in endometrial carcinoma in relation to clinicopathological parameters. Materials and methods This study included 62 endometrial carcinoma specimens, classified as 20 biopsies of serous carcinoma and 42 endometrioid carcinomas. All specimens were subjected to immunohistochemistry using HMGA-2, p16, and PR antibodies. Results HMGA-2, p16, and PR showed significantly different expression between serous and endometrioid carcinomas. P16 showed more sensitivity and specificity (85 and 80.9%, respectively) than HMGA-2 (75 and 71.4%, respectively) in diagnosis of SEC. PR showed sensitivity and specificity of 88.1 and 90%, respectively, in diagnosis of EEC. Moreover, high HMGA-2 expression was significantly related to high tumor grade, advanced tumor stage, and presence of lymphovascular invasion. Conclusions HMGA-2 can be used as an adjunct biomarker in diagnosis of SEC, combined with p16 and PR. Moreover, HMGA-2 can be considered as a marker of aggressive tumor behavior in endometrial carcinoma.

Immunohistochemical Expression of “HE4” in Endometrial Hyperplasia versus Endometrial Endometrioid Carcinoma

Aim &#x0D; Endometrial cancer is the most common cancer of the female genital tract. No effective biomarkers currently exist to allow for an efficient risk classification of endometrial carcinoma. Human epididymis protein 4 (HE4) overexpression is first observed in ovarian cancer tissue and subsequent research has shown that the HE4 overexpression has also been observed in patients with endometrial carcinoma. To our knowledge, this marker was evaluated in small number of research studies in cases of endometrial carcinoma versus hyperplasia. This has inspired us to test for immunohistochemical expression of HE4 in endometrial endometrioid carcinoma and hyperplastic endometria and to correlate HE4 expression with various prognostic pathological parameters including International Federation of Gynecology and Obstetrics (FIGO) grading and staging.&#x0D; Methods &#x0D; Immunohistochemical staining for HE4 was performed on paraffin-embedded sections of forty cases of endometrial endometrioid carcinoma and thirty cases of endometrial hyperplasia: including 15 cases of non-atypical hyperplasia and 15 cases of atypical hyperplasia. A histochemical score was used to evaluate HE4 expression by the tumor cells.&#x0D; Results&#x0D; In this study, HE4 overexpression level was significantly higher in endometrial endometrioid carcinoma than endometrial hyperplasia and significantly higher than non-atypical endometrial hyperplasia (P&lt;0.05). HE4 strong expression was detected in 20% of atypical endometrial hyperplasia, but no statistical significance was detected between atypical hyperplasia and endometrial carcinoma. HE4 overexpression showed statistically significant positive correlation with FIGO grading, FIGO staging, and depth of myometrial invasion.&#x0D; Conclusion:&#x0D; During interpretation of endometrial biopsies of atypical hyperplasia, HE4 strong expression might raise the possibility of the presence of coexisting adenocarcinoma not biopsied or even warning of a near future malignant transformation. Also, strong expression of HE4 by tissue biopsy of adenocarcinoma should be reported as this might predict higher grade and stage of the tumor, a point that should be considered by surgeons while performing hysterectomy. These results should be further confirmed by extending the study on a large scale, correlation of HE4 expression with the molecular classification of Tumor Cancer Genome Atlas and long term follow up are required to establish the prognostic significance of HE4 expression in endometrial carcinoma and atypical hyperplasia.&#x0D; Keywords: Endometrial carcinoma, Endometrial hyperplasia, HE4, Immunohistochemistry.

Prognostic and clinicopathological significance of TMEFF2, SMOC-2, and SOX17 expression in endometrial carcinoma

Backgroundthere is a need for novel biomarkers and targeting therapies for predicting Endometrial carcinoma (EC) progression and recurrence. TMEFF2 is a gene that was found to play a role in EMT. SMOC-2 is expressed in embryogenesis and it was identified as a recent stem cell-related gene that has a role in cancer progression. SRY-box 17 (SOX17) is a member of the SRY-related HMG-box (SOX) family of transcription factors. Dysregulation or downregulation of SOX17 expression was found in many cancer tissues.Aim: In the present study, we aimed to assess the tissue protein expressions of TMEFF2, SMOC-2, and SOX17 in EC using immunohistochemistry to evaluate their clinicopathological values and prognostic roles in EC patients.PATIENTS AND METHODS: This is prospective cohort study included 120 patients with EC. Sections from 120 paraffin blocks were retrieved and stained with TMEFF2, SMOC-2, and SOX17 using immunohistochemistry, the expression of markers in all tissue samples was assessed, analyzed and correlation of pathological parameters with the levels of expression was done. All patients were followed up till death or till the last known alive data for about 50 months (range from 25 to 60).RESULTS: TMEFF2, SMOC-2 expression was correlated with the presence of lymph node metastases (p = 0.023), distant metastasis (p = 0.039) recurrence of the tumor after successful therapy, overall survival, and disease-free survival (p < 0.001). SOX17 positive expression was positively correlated with low grade (p = 0.019), absence of lymph node metastasis (p = 0.001), absence of distant metastasis (p = 0.013), low stage (p = 0.03), and its negative expression was positively correlated with recurrence of the tumor after successful therapy, overall survival and disease-free survival (p = 0.001).In conclusion, we demonstrated that both TMEFF2 and SMOC-2 were highly expressed in EC and were associated with a shortened survival rate, dismal outcome, and poor prognosis in EC patients. While SOX17 expression was related to a favorable outcome and its down-regulation was associated with dismal EC patient's survival.