scholarly journals RNF183 Is a Prognostic Biomarker and Correlates With Tumor Purity, Immune Infiltrates in Uterine Corpus Endometrial Carcinoma

2020 ◽  
Vol 11 ◽  
Author(s):  
Rong Geng ◽  
Yuhua Zheng ◽  
Lijie Zhao ◽  
Xiaobin Huang ◽  
Rong Qiang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endometrial Cancer ◽  
Endometrial Carcinoma ◽  
Progression Free Survival ◽  
M2 Macrophage ◽  
Free Survival ◽  
Uterine Corpus ◽  
Immune Infiltration ◽  
Tumor Purity ◽  
High Level

RNF183, a member of the E3 ubiquitin ligase, has been shown to involve in carcinogenesis and proposed as one of the biomarkers in Uterine Corpus Endometrial Carcinoma (UCEC). However, no research focused on the role of RNF183 in UCEC. We analyzed the expression and immune infiltration of RNF183 in UCEC. TIMER, UALCAN, and GEPIA were used to analyze the gene expression of RNF183. We emplored Kaplan-Meier Plotter to examine the overall survival and progression-free survival of RNF183, and applied GeneMANIA to identify RNF183-related functional networks. LinkedOmics was helpful to identify the differential gene expression of RNF183, and to further analyze gene ontology and the genome pathways in the Kyoto Protocol. Finally, we used TIMER to investigate the immune infiltration of RNF183 in UCEC. Otherwise, we partly verified the results of bioinformatics analysis that RNF183 controlled ERα expression in ERα-positive Ishikawa cells dependent on its RING finger domain. We also found that ERα increased the stability of RNF183 through the post-translational mechanism. Together, patients with a high level of RNF183 harbor favorable overall and progression-free survival. High expression of RNF183 was associated with a low stage, endometrioid, and TP53 Non-Mutant status in endometrial cancer. The RNF183 expression was greater at higher expression and the tumor stage was greater at the lower level. On the side of immunization, high level of RNF183 in UCEC is negatively related to tumor purity, infiltrating levels of CD4 + T cells, neutrophils, and dendritic cells. Besides, the expression of RNF183 in UCEC is significantly correlated with the expression of several immune cell markers, including B cell, M1 macrophage marker, M2 Macrophage, Dendritic cell, Th1 markers, Th2 markers, Treg markers, and T cell exhaustion markers, indicating its role in regulating tumor immunity. These results suggested that RNF183 may be considered as a novel prognostic factor in endometrial cancer and an early diagnostic indicator for patients with UCEC.

Why Routine Clinical Follow-up for Patients With Early Stage Endometrial Cancer Is Not Always Necessary: A Study on Women in South Wales

2014 ◽  
Vol 24 (3) ◽  
pp. 556-563 ◽  
Author(s):  
Lilly Aung ◽  
Robert E.J. Howells ◽  
Kenneth C.K. Lim ◽  
Emma Hudson ◽  
Peter W. Jones
Keyword(s):  
Endometrial Cancer ◽  
Confidence Interval ◽  
Endometrial Carcinoma ◽  
Early Stage ◽  
Progression Free Survival ◽  
Disease Recurrence ◽  
Hazard Ratio ◽  
Free Survival ◽  
South Wales

ObjectiveThis study aimed to examine the existing methods of follow-up in women who have undergone treatment of early endometrial carcinoma in South Wales and to assess if they are appropriate.DesignThis study used a retrospective analysis of follow-up data.SettingThis study was performed in the Virtual Gynaecological Oncology Centre, South Wales, United Kingdom.SampleThis study sample is composed of 552 women.MethodsData regarding follow-up were collected retrospectively from patient case notes and computerized data systems. Data were analyzed using the Pearson χ2 test, Cox proportional hazard regression analysis, and Kaplan-Meier curves.Main Outcome MeasuresThis study aimed to determine whether routine follow-up was beneficial in detecting disease recurrence and whether outcome was influenced by routine follow-up.ResultsBetween January 1, 2000, and December 31, 2010, 552 women were treated for early stage endometrial carcinoma. The 5-year survival was 81%, and the 5-year progression-free survival was 77%. Of these 552 women, 81 (15%) developed a disease recurrence; the majority (61/81 [75%]) recurred within 3 years. The median survival was 35 months compared with 47 months in patients who did not develop a recurrence. Of the 81 patients, 73 (90%) were symptomatic and only 5 patients were truly asymptomatic at follow-up. The most important and significant prognostic factor was “recurrent disease” with overall survival (hazard ratio, 2.20; P < 0.001; 95% confidence interval, 1.75–2.65) and progression-free survival (hazard ratio, 2.52; P < 0.001; 95% confidence interval, 2.09–2.95). “Asymptomatic recurrence” was not an independent predictor of outcome.ConclusionsRoutine follow-up for early endometrial cancer is not beneficial for patients because most were symptomatic at the time of detection. It does not significantly improve the outcome. We propose altering the follow-up time regimen and adopting alternative follow-up strategies for women in South Wales.

scholarly journals Lenvatinib and pembrolizumab in the treatment of metastatic endometrial cancer: literature review and case report

2021 ◽  
pp. 124-128
Author(s):  
A. A. Rumyantsev
Keyword(s):  
Endometrial Cancer ◽  
Endometrial Carcinoma ◽  
Objective Response Rate ◽  
Response Rate ◽  
Therapeutic Option ◽  
Objective Response ◽  
Progression Free Survival ◽  
Response To Therapy ◽  
Effective Therapeutic Option ◽  
High Level

In 2019 in Russia endometrial carcinoma was diagnosed in 27151 patients, 6820 women died from the disease. The standard of frontline therapy for patients with advanced endometrial carcinoma is platinum and taxane-based chemotherapy with satisfactory efficacy – the median progression-free survival is about 13 months, and up to 50% of patients achieve objective response to therapy. On the other hand, for patients with recurrent endometrial cancer after frontline chemotherapy the results of chemotherapy remained generally unsatisfactory, the objective response rate to standard treatment was about 10 to 15%. During the last few years there significant progress has been made in this area – studies identified a subgroup of patients with a high level of microsatellite instability (MSI-high) highly sensitive to pembrolizumab therapy. In this subset of patients, who account for up to 25% of patients with metastatic endometrial cancer, the objective response rate to pembrolizumab monotherapy is up to 57%. Further studies have shown that the addition of lenvatinib to pembrolizumab therapy may be a highly effective therapeutic option for patients without MSI-high. This article describes a clinical case of the successful therapy of a patient with platinumresistant endometrial carcinoma with a combination of pembrolizumab and lenvatinib. 

scholarly journals The effect of myometrial invasion on prognostic factors and survival analysis in endometrial carcinoma

1970 ◽  
Vol 19 (4) ◽  
pp. 3235-3241
Author(s):  
Cem Dane ◽  
Sait Bakir
Keyword(s):  
Overall Survival ◽  
Endometrial Cancer ◽  
Prognostic Factors ◽  
Survival Rate ◽  
Endometrial Carcinoma ◽  
Myometrial Invasion ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Free Survival ◽  
The Relationship

Background: We investigated the relationship between myometrial invasion and the prognostic factors on overall and progression free survival in endometrial carcinoma.Methods: 122 cases operated with endometrial cancer were included into the study. Progression-free survival and overall survival were evaluated according to degree of myometrial invasion. We also investigated the relationship between myometrial invasion and prognostic factors. Results: The 5- year progression-free survival rate was 90 % in stage I, 66 % in stage II, 32 % in stage III and 60 % in stage IV. The 5- year overall survival rate was 95 % in stage I, 89 % in stage II, 49 % in stage III and 30 % in stage IV. The progression free survival and overall survival for patients with more than 50 % myometrial invasion were detected 67 % at 58 months and 66 % at 60 months, respectively. The clinicopathological variables that significantly correlated with myometrial invasion of more than 50 % were as follows: pelvic lymph node metastasis (p: 0,00029-OR: 11.2), cervical stromal invasion (p: 0008-OR:7.9), LVSI (p< 0.0001-OR: 16.5).Conclusion: The depth of myometrial invasion is one of the most important prognostic indicators and determinants of therapy in endometrial cancer. Keywords: Endometrial carcinoma; Progression free survival; Overall survival; Prognostic factors.

A Phase 2, Randomized, Open-Label Study of Irosustat Versus Megestrol Acetate in Advanced Endometrial Cancer

2017 ◽  
Vol 27 (2) ◽  
pp. 258-266 ◽  
Author(s):  
Patricia Pautier ◽  
Ignace Vergote ◽  
Florence Joly ◽  
Bohuslav Melichar ◽  
Elzbieta Kutarska ◽  
...  
Keyword(s):  
Overall Survival ◽  
Endometrial Cancer ◽  
Adverse Events ◽  
Confidence Interval ◽  
Progression Free Survival ◽  
Megestrol Acetate ◽  
Phase 2 ◽  
Open Label ◽  
Free Survival ◽  
Recurrent Endometrial Cancer

ObjectiveAdvanced/metastatic or recurrent endometrial cancer has a poor prognosis. Malignant endometrial tissue has high steroid sulphatase (STS) activity. The aim of this study was to evaluate STS as a therapeutic target in patients with endometrial cancer.MethodsThis was a phase 2, multicenter, international, open-label, randomized (1:1), 2-arm study of the STS inhibitor oral irosustat 40 mg/d versus oral megestrol acetate 160 mg/d in women with advanced/metastatic or recurrent estrogen receptor–positive endometrial cancer. The primary end point was the proportion of patients without progression or death 6 months after start of treatment. Secondary end points included progression-free survival, time to progression, overall survival, and safety.ResultsSeventy-one patients were treated (36 with irosustat, 35 with megestrol acetate). The study was prematurely stopped after futility analysis. Overall, 36.1% and 54.1% of patients receiving irosustat or megestrol acetate had not progressed or died at 6 months, respectively. There were no statistically significant differences between irosustat and megestrol acetate in response and overall survival rates. Irosustat patients had a median progression-free survival of 16 weeks (90% confidence interval, 9.0–31.4) versus 40 weeks (90% confidence interval, 16.3–64.0) in megestrol acetate patients. Treatment-related adverse events occurred in 20 (55.6%) and 13 (37.1%) patients receiving irosustat or megestrol, respectively. Most adverse events in both groups were grade 1 or 2.ConclusionsAlthough irosustat monotherapy did not attain a level of activity sufficient for further development in patients with advanced/recurrent endometrial cancer, this study confirms the activity of hormonal treatment (megestrol acetate) for this indication.

scholarly journals Overexpression of the OCT-1 Gene Is a Biomarker Associated with Poor Outcomes in Diffuse Large B-Cell Lymphoma (DLBCL) - Data from a Retrospective Cohort from Latin America: Defining a Very High-Risk Clinical-Molecular Subgroup

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 41-42
Author(s):  
Luis Alberto de Padua Covas Lage ◽  
Gisele Rodrigues Gouveia ◽  
Suzete Cleusa Ferreira ◽  
Sheila Aparecida Coelho de Siqueira ◽  
Abrahão Elias Hallack Neto ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Risk ◽  
B Cell ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Prognostic Impact ◽  
Molecular Subgroup ◽  
Free Survival ◽  
Very High

Introduction: Diffuse large B-cell lymphoma (DLBCL) is the most frequent lymphoid malignancy, representing 30-40% of all non-Hodgkin's lymphomas (NHLs). They comprise a group of aggressive and heterogeneous neoplasms in terms of clinical presentation, response to therapy and prognosis. The OCT-1 gene is a member of the homodomain-POU family of transcriptional regulators of B-lymphoid differentiation. OCT-1 acts by controlling the expression of specific B-cell genes, such as BCL-2, a potent inhibitor of apoptosis that is essential for the differentiation of B-cells in the germinal center. These genes can be expressed in DLBCL, but the role of BCL-2 in its prognosis has been contradictory and the prognostic impact of the OCT-1 gene has not yet been tested in this lymphoma. Methods: In this observational, retrospective, single-center study, we investigated the prognostic impact of BCL-2 and OCT-1 gene expression in Brazilian patients with DLCBL treated with immunopolychemotherapy R-CHOP in a real-world context. The BCL-2 and OCT-1 genes were assessed in 78.5% (77/98) DLBCL patients, and the RNA for quantitative real-time PCR (qRT-PCR) was isolated from formalin-fixed and paraffin-embedded (FFPE) samples. The values obtained for gene expression were transformed into categorical variables according to their medians (6.27 for BCL-2 and 24.5 for OCT-1). The association between clinical and laboratory variables and results of gene expression was verified by the Fischer test. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Univariate analysis was performed using Cox's bivariate regression method and multivariate analysis using Cox multiple regression methodology. Results: The median age of the cohort was 54.5 years (15-84), 50% (49/98) were male, 49.4% (38/77) and 51.4% (40/77) showed expression of OCT-1 and BCL- 2 ≥ median, respectively. The clinical characteristics of the 98 Brazilian patients with DLBCL that comprised our cohort are summarized in Table 1. The overall response rate (ORR) in all patients was 68.4% (67/98), 65.3% (64/98) showed a complete response (CR), and 3.1% (3/98) showed partial response (PR), while 6.1% (6/98) were primary refractory. With a median follow-up of 3.77 years (95% CI: 3.2-4.1), the median overall survival (OS) was 5.43 years (95% CI: 2.2-NR) and the median progression-free survival (PFS) was 5.15 years (95% CI: 2.9-NR). The 5-year OS and PFS was 54.2% (42.2% -64.8%) and 52.0% (40.1-62.6%), respectively. In the univariate analysis OCT-1 ≥ median was associated with shortened OS (HR: 2.45, 95% CI: 1.21-4.96, p = 0.013) and PFS (HR: 2.27, 95% CI: 1.14-4.51, p = 0.019). Overexpression of BCL-2 was associated with worse PFS (HR: 2.00, 95% CI: 1.02-3.95, p = 0.043). Subgroup analysis showed that OCT-1 overexpression predominated in elderly individuals (≥ 60 years) in a statistically significant mode (29/38 cases - 76.3%, p = 0.029). It was also observed that overexpression of OCT-1 was associated with worse OS in the high-risk adjusted International Prognostic Index (aIPI) subgroup (p = 0.048) - Figure 1, and worse PFS in patients ≥ 60 years old (p = 0.025) - Figure 2. In the multivariate analysis, overexpression of OCT-1 was associated with poor PFS (HR: 2.22, 95% CI: 1.06-4.76, p = 0.035). Conclusion: In this study, we demonstrated that overexpression of the OCT-1 gene was an independent prognostic factor associated with adverse outcomes in Brazilian patients with DLCBL. We also show that in patients with unfavorable risk, such as the elderly and those with intermediate-high and high-risk IPI, overexpression of OCT-1 contributed to the identification of a very high-risk clinical-molecular subgroup, where the results with standard R-CHOP therapy are unsatisfactory, and they may benefit from intensified therapeutic strategies. Our results are preliminary and need to be validated in subsequent studies of prospective nature and with an expanded sample. Disclosures No relevant conflicts of interest to declare.

scholarly journals Outcome of Endometrial Cancer Stage IIIA with Adnexa or Serosal Involvement Only

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Jan J. Jobsen ◽  
Lambert Naudin ten Cate ◽  
Marnix L. M. Lybeert ◽  
Astrid Scholten ◽  
Elzbieta M. van der Steen-Banasik ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Endometrial Carcinoma ◽  
Distant Metastasis ◽  
Cancer Stage ◽  
Disease Specific Survival ◽  
Stage Iiia ◽  
Free Survival ◽  
Locoregional Failure ◽  
Distant Metastasis Free Survival ◽  
Disease Specific

Objective. The aim of this study is to look at possible differences in outcome between serosa and adnexal involvement stage IIIA endometrial carcinoma.Methods. 67 patients with stage IIIA endometrial carcinoma were included, 46 with adnexal involvement and 21 with serosa. A central histopathological review was performed.Results. The 7-year locoregional failure rate was (LRFR) 2.2% for adnexal involvement and 16.0% for involvement of the serosa (P=.0522). The 7-year distant metastasis-free survival was 72.7% for adnexal involvement and 58.7% for serosa (P=.3994). The 7-year disease-specific survival (DSS) was 71.8% for patients with adnexal involvement and 75.4% for patients with serosa.Conclusion. Endometrial carcinoma stage IIIA with involvement of the adnexa or serosa showed to have a comparable disease-specific survival. Locoregional control was worse for serosa involvement compared to adnexa.

Concurrent 5-Fluorouracil, Mitomycin C and Radiation, with or without Brachytherapy, in Recurrent Endometrial Cancer: A Scoring System to Predict Clinical Response and Outcome

2005 ◽  
Vol 91 (3) ◽  
pp. 215-220 ◽  
Author(s):  
Daniela Smaniotto ◽  
Giuseppe D'Agostino ◽  
Stefano Luzi ◽  
Vincenzo Valentini ◽  
Gabriella Macchia ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Mitomycin C ◽  
Local Control ◽  
Progression Free Survival ◽  
External Beam Radiation ◽  
External Beam ◽  
Beam Radiation ◽  
Free Survival ◽  
Recurrent Endometrial Cancer ◽  
Grade 3

Aims and background This prospective, phase II study aimed to test the efficacy of concurrent 5-fluorouracil, mitomycin C and radiation, with or without brachytherapy, on the clinical outcome of a series of recurrent endometrial cancer patients and to determine the prognostic impact of a subset of factors. Methods Thirty patients with locally recurrent, nonmetastatic endometrial cancer received external beam radiation (4-week split course: 23.4 + 23.4 Gy) plus two courses of concomitant chemotherapy (5-fluorouracil, 96-h continous infusion, days 1-4; 1 g/m2/day; mitomycin C, 10 mg/m2, bolus iv, day 1). Nineteen patients (63.3%) underwent endocavitary, low-dose brachytherapy boost (20-25 Gy); eight patients (26.7%) received external beam radiation boost (14-20 Gy). Results Eleven complete responses (36.7%), 11 partial responses (36.7%), 6 disease stabilizations (20.0%) and 2 progressions (6.6%) were observed. After a median follow-up of 27 months (range, 1-108), overall actuarial 3-year survival, progression-free survival and local progression-free survival were 46.8%, 35.2% and 41.2%, respectively. Two patients (6.7%) experienced hematological grade 3 toxicity. Two patients (6.7%) had grade 3 intestinal toxicity. Severe late toxicity was infrequent, only 3 patients showing severe vaginal stenosis (10.0%). A clinical score of 0 to 1 was assigned to each patient on the basis of the absence (score = 0) or presence (score = 1) of any of the following prognostic factors: time between surgery and recurrence shorter than 12 months, pelvic wall site of recurrence, positive lymph nodes, hemoglobin <11 g/dL. With this device, it was clear that patients with a low score had a significantly better outcome (clinical remission: 77.2% of patients with a score <2 vs 25.0% of patients with a score ≥2, P = 0.009), better local control of the disease (50.2% vs. 0 at 3 years, P = 0.014,) and better overall survival (65.8% vs 0 at 3 years, P = 0.003). Conclusions Our data suggest that this combined modality therapy was relatively well tolerated and resulted in reasonable local control and survival. The scoring system proved to be helpful in identifying patients with the best chance of benefiting from the treatment.

MDR1 gene expression in endometrial carcinoma

2003 ◽  
Vol 13 (5) ◽  
pp. 673-677
Author(s):  
M. C. Terek ◽  
O. Zekioglu ◽  
F. Sendag ◽  
F. Akercan ◽  
A. Ozsaran ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endometrial Cancer ◽  
Endometrial Carcinoma ◽  
Clear Cell ◽  
Mdr1 Gene ◽  
Histologic Subtype ◽  
P Glycoprotein ◽  
Mdr1 Gene Expression ◽  
Premenopausal Patients ◽  
The Mean

The objective of the present study was to determine the MDR1 gene expression in endometrial cancer. Twenty-six newly diagnosed patients with endometrial carcinoma were included in this study. Patients were treated with surgery followed by adjuvant radiotherapy. Four- to six-micrometer sections of the archival paraffin-embedded blocks were cut, deparaffinized, and stained by immunohistochemical technique using P-glycoprotein dye. Endothelial cell staining was used as the positive control of the dye. Immunostaining was categorized from 0% to 100% based on the percentage of cells stained by examining 3–4 high-power fields. The mean P-glycoprotein immunoreactivity for the whole study group was 17 ± 25% (0–90). The mean P-glycoprotein immunoreactivity was 21 ± 26% (0–90) for the endometrioid histology and 6 ± 13% (0–30) for the clear cell histology. P-glycoprotein immunoreactivity was not detected in a case of mucinous histologic subtype. There was a significant negative correlation between age and P-glycoprotein immunoreactivity (r = −0.530, P = 0.005). The P-glycoprotein immunoreactivity was found to be 30% positive in only one case of clear cell histologic type out of five. However, P-glycoprotein immunoreactivity was not significantly lower in clear cell histologic subtype compared with endometrioid subtype of endometrial cancer (P = 0.116). P-glycoprotein immunoreactivity was found to be 0% in grade 1 (n = 2), 22 ± 28% in grade 2 (n = 17), and 8 ± 14% in grade 3 (n = 7) patients (P = 0.273). Premenopausal patients were found to have a significantly higher P-glycoprotein expression (40 ± 33)% vs. 11 ± 20%, P = 0.04). P-glycoprotein immunoreactivity was found to be less with advanced age in endometrial carcinoma. However, premenopausal patients were found to have a significantly higher P-glycoprotein expression.

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