scholarly journals AKR1B1 and AKR1B10 as Prognostic Biomarkers of Endometrioid Endometrial Carcinomas

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3398
Author(s):  
Marko Hojnik ◽  
Snježana Frković Grazio ◽  
Ivan Verdenik ◽  
Tea Lanišnik Rižner
Keyword(s):  
Endometrial Cancer ◽  
Disease Free Survival ◽  
Prognostic Biomarkers ◽  
Survival Prediction ◽  
Paraffin Sections ◽  
Free Survival ◽  
Endometrioid Endometrial Cancer ◽  
Cox Analysis ◽  
Endometrial Carcinomas ◽  
Disease Free

The roles of aldo-keto reductase family 1 member B1 (AKR1B1) and B10 (AKR1B10) in the pathogenesis of many cancers have been widely reported but only briefly studied in endometrial cancer. To clarify the potential of AKR1B1 and AKR1B10 as tissue biomarkers of endometrial cancer, we evaluated the immunohistochemical levels of AKR1B1 and AKR1B10 in tissue paraffin sections from 101 well-characterized patients with endometrioid endometrial cancer and 12 patients with serous endometrial cancer and compared them with the clinicopathological data. Significantly higher immunohistochemical levels of AKR1B1 and AKR1B10 were found in adjacent non-neoplastic endometrial tissue compared to endometrioid endometrial cancer. A trend for better survival was observed in patients with higher immunohistochemical AKR1B1 and AKR1B10 levels. However, no statistically significant differences in overall survival or disease-free survival were observed when AKR1B1 or AKR1B10 were examined individually in endometrioid endometrial cancer. However, analysis of AKR1B1 and AKR1B10 together revealed significantly better overall and disease-free survival in patients with both AKR1B1 and AKR1B10 staining above the median values compared to all other patients. Multivariant Cox analysis identified strong AKR1B1 and AKR1B10 staining as a statistically important survival prediction factor. Conversely, no significant differences were found in serous endometrial cancer. Our results suggest that AKR1B1 and AKR1B10 play protective roles in endometrioid endometrial cancer and show potential as prognostic biomarkers.

scholarly journals ATR Mutation in Endometrioid Endometrial Cancer Is Associated With Poor Clinical Outcomes

2009 ◽  
Vol 27 (19) ◽  
pp. 3091-3096 ◽  
Author(s):  
Israel Zighelboim ◽  
Amy P. Schmidt ◽  
Feng Gao ◽  
Premal H. Thaker ◽  
Matthew A. Powell ◽  
...  
Keyword(s):  
Dna Damage ◽  
Overall Survival ◽  
Endometrial Cancer ◽  
Dna Damage Response ◽  
Disease Free Survival ◽  
Free Survival ◽  
Damage Response ◽  
Endometrioid Endometrial Cancer ◽  
Disease Free ◽  
Exon 10

Purpose Mutations in the DNA damage response gene ATR (exon 10 A10 mononucleotide repeat) have been previously described in endometrial and other cancers with defective DNA mismatch repair. In vitro studies showed that endometrial cancer cell lines with A10 repeat tract truncating mutations have a failure in the ATR-dependent DNA damage response. Cell lines carrying A10 mutations fail to trigger Chk1 activation in response to ionizing radiation and topoisomerase inhibitors. We sought to determine the frequency and clinicopathologic significance of ATR mutations in patients with endometrioid endometrial cancer. Patients and Methods The ATR exon 10 A10 repeat was analyzed by direct sequencing in 141 tumors with microsatellite instability (MSI-positive) and 107 microsatellite stable (MSI-negative) tumors. The relationships between mutations and clinicopathologic variables, including overall and disease-free survival, were assessed using contingency table tests and Cox proportional hazard models. Results ATR mutations were identified in 12 cases (4.8%; three cases with insertions and nine cases with deletions). Mutations occurred exclusively in MSI-positive tumors (P = .02), with an overall mutation rate of 8.5%. Mutation was not associated with age, race, surgical stage, International Federation of Gynecology and Obstetrics grade, or adjuvant treatment. Multivariate analyses revealed a significant association with reduced overall survival (hazard ratio [HR] = 3.88; 95% CI, 1.64 to 9.18; P = .002) and disease-free survival (HR = 4.29; 95% CI, 1.48 to 12.45; P = .007). Conclusion Truncating ATR mutations in endometrial cancers are associated with biologic aggressiveness as evidenced by reduced disease-free and overall survival. Knowledge of ATR mutation status may hold promise for individualized treatment and targeted therapies in patients with endometrial cancer.

scholarly journals Microsatellite Instability as a Maker of Prognosis: a Systematic Review and Meta-analysis of Endometrioid Endometrial Cancer Survival Data

2022 ◽  
Author(s):  
Jing-ping Xiao ◽  
Ji-sheng Wang ◽  
Yuan-yu Zhao ◽  
Jiang Du ◽  
Yunzi Wang
Keyword(s):  
Overall Survival ◽  
Endometrial Cancer ◽  
Microsatellite Instability ◽  
Early Stage ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Free Survival ◽  
Endometrioid Endometrial Cancer ◽  
Disease Free

Abstract Introduction To investigate whether microsatellite instability (MSI) is an important prognostic biomarker for endometrioid endometrial cancer (EEC).Methods The PubMed, EMBASE and the Cochrane Cooperative Library databases were searched from inception to July 2021. Overall survival, disease-free survival, progression-free survival, EEC-specific survival, recurrence-free survival and the recurrence rate were pooled to analyze the correlation between MSI and EEC. In addition, Egger’s regression analysis and Begg’s test were used to detect publication bias.Results 17 studies met the inclusion criteria and were included in our meta-analysis with a sample size of 4723, and the included patients with endometrioid cancer (EC) all were EEC. The pooled hazard ratios (HR) in patients with EEC shown that MSI was significantly associated with shorter overall survival [HR=1.37, 95% confidence interval (CI) (1.00-1.86), p=0.048, I2=60.6%], shorter disease-free survival [HR=1.99, 95% CI (1.31-3.01), p=0.000, I2=67.2%], shorter EEC-specific survival [HR=2.07, 95% CI (1.35-3.18), p=0.001, I2=31.6%] and a higher recurrence rate [Odds ratios (OR)=2.72, 95% CI (1.56-4.76), p=0.000, I2=0.0%]. In the early-stage EEC subgroup, MSI was significantly associated with shorter overall survival [HR=1.47, 95% CI (1.11-1.95), p=0.07], shorter disease-free survival [HR=4.17, 95% CI (2.37-7.41), p=0.000], and shorter progression-free survival [HR=2.41, 95% CI (1.05-5.54), p=0.039]. No significant heterogeneity was observed in overall survival (I2=20.9%), disease-free survival (I2=0.0%), or progression-free survival (I2=0.0%) in patients with early-stage EEC. Meanwhile, publication bias was not observed, and the p-value for Egger’s test of overall survival, disease-free survival, and EEC-specific survival were p=0.131, p=0.068 and p=0.987, respectively.Conclusion MSI is likely an important biomarker for poor prognosis in patients with EEC, and this correlation is even more certain in patients with early-stage EEC.

scholarly journals Circulating tumor DNA as a prognostic marker in high-risk endometrial cancer

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Weiwei Feng ◽  
Nan Jia ◽  
Haining Jiao ◽  
Jun Chen ◽  
Yan Chen ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
High Risk ◽  
Tumor Recurrence ◽  
Disease Free Survival ◽  
Circulating Tumor Dna ◽  
Plasma Samples ◽  
Free Survival ◽  
Tumor Relapse ◽  
Disease Free ◽  
Tumor Dna

Abstract Background Currently, there is no reliable blood-based marker to track tumor recurrence in endometrial cancer (EC) patients. Liquid biopsies, specifically, circulating tumor DNA (ctDNA) analysis emerged as a way to monitor tumor metastasis. The objective of this study was to examine the feasibility of ctDNA in recurrence surveillance and prognostic evaluation of high-risk EC. Methods Tumor tissues from nine high-risk EC patients were collected during primary surgery and tumor DNA was subjected to next generation sequencing to obtain the initial mutation spectrum using a 78 cancer-associated gene panel. Baseline and serial post-operative plasma samples were collected and droplet digital PCR (ddPCR) assays for patient-specific mutations were developed to track the mutations in the ctDNA in serial plasma samples. Log-rank test was used to assess the association between detection of ctDNA before or after surgery and disease-free survival. Results Somatic mutations were identified in all of the cases. The most frequent mutated genes were PTEN, FAT4, ARID1A, TP53, ZFHX3, ATM, and FBXW7. For each patient, personalized ddPCR assays were designed for one-to-three high-frequent mutations. DdPCR analysis and tumor panel sequencing had a high level of agreement in the assessment of the mutant allele fractions in baseline tumor tissue DNA. CtDNA was detected in 67% (6 of 9) of baseline plasma samples, which was not predictive of disease-free survival (DFS). CtDNA was detected in serial post-operative plasma samples (ctDNA tracking) of 44% (4 of 9) of the patients, which predicted tumor relapse. The DFS was a median of 9 months (ctDNA detected) versus median DFS undefined (ctDNA not detected), with a hazard ratio of 17.43 (95% CI, 1.616–188.3). The sensitivity of post-operative ctDNA detection in estimating tumor relapse was 100% and specificity was 83.3%, which was superior to CA125 or HE4. Conclusions Personalized ctDNA detection was effective and stable for high-risk EC. CtDNA tracking in post-operative plasma is valuable for predicting tumor recurrence.

Features associated with survival and disease-free survival in early endometrial cancer

1990 ◽  
Vol 31 (2) ◽  
pp. 209-210
Author(s):  
GP Sutton ◽  
HE Geisler ◽  
FB Stehman ◽  
PCM Young ◽  
TM Kimes ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Disease Free Survival ◽  
Free Survival ◽  
Disease Free

Expression of L1CAM and KI-67 in Endometrial Cancer of Egyptian Females: Clinical Impact and Survival

2020 ◽  
Vol 106 (1_suppl) ◽  
pp. 36-36
Author(s):  
Fatma Gharib ◽  
Dareen Abd elaziz mohamed ◽  
Basma Saed Amer
Keyword(s):  
Endometrial Cancer ◽  
Endometrial Adenocarcinoma ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Rank Test ◽  
Significant Heterogeneity ◽  
Ki 67 ◽  
Free Survival ◽  
Disease Free ◽  
L1cam Expression

Introduction: Endometrial adenocarcinoma is characterized by a good prognosis. However, the disease response shows a significant heterogeneity. Treatment of endometrial cancer (EC) is still based on clinico-pathological parameters, which have limited role in risk stratification. There is a need for more determinant markers, such as L1 Cell Adhesion Molecule (L1CAM), to identify patients at higher risk of relapse and tailor a more convenient treatment. L1CAM has a capacity to enhance cell motility and promote tumor invasion in different malignancies. In Egypt, the incidence rate of EC is growing over time. Especially in Elgharbiah governorate (home of this study). L1CAM expression and Ki-67 was reported and compared with other clinico-pathological criteria. Method: Seventy-six female patients of endometrial carcinomas were involved in this prospective study. The patients were treated and followed up at Tanta University Hospitals in the period between January 2015 to April 2019. L1CAM expression and Ki-67 was detected by immuno-histochemical exam and compared with other clinico-pathological criteria. Survival was assessed and compared by Kaplan-Meier curves and log-rank test. Results: Positive L1CAM expression was detected in 17 patients (22.4%) and was significantly correlated with unfavorable prognostic factors such as higher stage and grade ( P= 0.021 and P =0.001 respectively), lympo-vascular invasion ( P <0.001), non-endometroid type ( P <0.027) and Ki-67 ( P= 0.003). Univariate analysis revealed that: positive L1CAM; higher tumor grade; high stage; and non-endometrioid type were significantly associated with shorter disease-free survival (DFS) but no significant correlation was detected between Ki-67 and DFS. In multivariate analysis, positive L1CAM remained statistically significant with DFS [P =0.045; 95%CI (1.028:11.17); HR=3.38]. Conclusion: Our study indicates that L1CAM expression and Ki-67 are significantly associated with poor tumor characteristics. L1CAM is significantly associated with shorter disease-free survival and may be a helpful tool as a part of a simple clinical molecular classification for EC.

scholarly journals Prospective Cohort Study of Pre- and Postdiagnosis Physical Activity and Endometrial Cancer Survival

2020 ◽  
Vol 38 (34) ◽  
pp. 4107-4117
Author(s):  
Christine M. Friedenreich ◽  
Linda S. Cook ◽  
Qinggang Wang ◽  
Renée L. Kokts-Porietis ◽  
Jessica McNeil ◽  
...  
Keyword(s):  
Physical Activity ◽  
Overall Survival ◽  
Endometrial Cancer ◽  
Cohort Study ◽  
Disease Free Survival ◽  
Activity Levels ◽  
Recreational Physical Activity ◽  
Free Survival ◽  
Physical Activity Levels ◽  
Disease Free

PURPOSE The aim of this study was to evaluate associations between pre- and postdiagnosis physical activity and survival in survivors of endometrial cancer by physical activity domain, intensity, dose (metabolic-equivalent task [MET]-hours/week/year), and change from pre- to postdiagnosis. METHODS We conducted a prospective cohort study in Alberta, Canada, of 425 women who were diagnosed with histologically confirmed invasive endometrial cancer between 2002 and 2006 and observed to 2019. The interviewer-administered Lifetime Total Physical Activity Questionnaire recorded prediagnosis (assessed at a median of 4.4 months after diagnosis) and postdiagnosis physical activity (assessed at a median of 3.4 years after diagnosis). Associations between physical activity and overall and disease-free survival were assessed using Cox proportional hazards models adjusted for age, stage, grade, treatments, body mass index, menopausal status, hormone therapy use, family history of cancer, and comorbidities. RESULTS After a median follow-up of 14.5 years, there were 60 deaths, including 18 endometrial cancer deaths, and 80 disease-free survival events. Higher prediagnosis recreational physical activity was statistically significantly associated with improved disease-free survival (> 14 v ≤ 8 MET-hours/week/year; hazard ratio [HR], 0.54; 95% CI, 0.30 to 0.96; Ptrend = .04), but not overall survival (HR, 0.56; 95% CI, 0.29 to 1.07; Ptrend = .06). Higher postdiagnosis recreational physical activity (> 13 v ≤ 5 MET-hours/week/year) was strongly associated with both improved disease-free survival (HR, 0.33; 95% CI, 0.17 to 0.64; Ptrend = .001) and overall survival (HR, 0.33; 95% CI, 0.15 to 0.75; Ptrend = .007). Participants who maintained high recreational physical activity levels from pre- to postdiagnosis also had improved disease-free survival (HR, 0.35; 95% CI, 0.18 to 0.69) and overall survival (HR, 0.43; 95% CI, 0.20 to 0.94) compared with those who maintained low physical activity levels. CONCLUSION Recreational physical activity, especially postdiagnosis, is associated with improved survival in survivors of endometrial cancer.

Correlation of TNFAIP8 overexpression with the proliferation, metastasis, and disease-free survival in endometrial cancer

Tumor Biology ◽  
2014 ◽  
Vol 35 (6) ◽  
pp. 5805-5814 ◽  
Author(s):  
Tianbo Liu ◽  
Hongyu Gao ◽  
Meng Yang ◽  
Tingting Zhao ◽  
Yunduo Liu ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Disease Free Survival ◽  
Free Survival ◽  
Disease Free

scholarly journals Prognostic Impact of Hypoxia-InduciblemiRNA-210in Patients with Lung Adenocarcinoma

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Jun Osugi ◽  
Yuka Kimura ◽  
Yuki Owada ◽  
Takuya Inoue ◽  
Yuzuru Watanabe ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Disease Free Survival ◽  
Inverse Correlation ◽  
Prognostic Impact ◽  
Free Survival ◽  
Cox Analysis ◽  
Medical University ◽  
Disease Stages ◽  
The Relationship ◽  
Disease Free

Objective. The aim of this study was to investigate the prognostic value ofMicroRNA-210(miR-210) expression in patients with non-small-cell lung cancer (NSCLC).Methods. We examined themiR-210expression of samples of 80 patients, who underwent surgical resection at Fukushima Medical University from 2004 to 2007, by using quantitative RT-PCR. The relationship betweenmiR-210expression and clinicopathological factors as well as histological subtype was statistically analyzed.Results.miR-210expression showed an inverse correlation with disease-free and overall survival in patients with NSCLC. Significant correlations were found betweenmiR-210expression and lymph node metastasis, late disease stages, and poor prognosis in patients with adenocarcinoma. Multivariate Cox analysis indicated thatmiR-210expression was an independent prognostic factor for disease-free survival in patients with adenocarcinoma.Conclusions. We showed thatmiR-210may be a prognostic biomarker for patients with NSCLC, especially for those with lung adenocarcinoma.

Impact of coexistent adenomyosis on outcomes of patients with endometrioid endometrial cancer: a propensity score-matched analysis

2018 ◽  
Vol 104 (1) ◽  
pp. 60-65 ◽  
Author(s):  
Hulya Ayik Aydin ◽  
Tayfun Toptas ◽  
Selen Bozkurt ◽  
Elif Pestereli ◽  
Tayup Simsek
Keyword(s):  
Endometrial Cancer ◽  
Propensity Score ◽  
Disease Free Survival ◽  
Tumor Grade ◽  
Multivariable Logistic Regression Model ◽  
Free Survival ◽  
Endometrioid Endometrial Cancer ◽  
The Common ◽  
Matched Comparison

Purpose: Despite the common occurrence of adenomyosis in endometrial cancer (EC), there is a paucity and conflict in the literature regarding its impact on outcomes of patients. We sought to compare outcomes of patients with endometrioid type EC with or without adenomyosis. Methods: A total of 314 patients were included in the analysis. Patients were divided into 2 groups according to the presence or absence of adenomyosis. Adenomyosis was identified in 79 patients (25.1%). A propensity score-matched comparison (1:1) was carried out to minimize selection biases. The propensity score was developed through multivariable logistic regression model including age, stage, and tumor grade as covariates. After performing propensity score matching, 70 patients from each group were successfully matched. Primary outcome of the study was disease-free survival (DFS), and the secondary outcomes were overall survival (OS) and disease-specific survival (DSS). Results: Median follow-up time was 61 months for the adenomyosis positive group and 76 months for the adenomyosis negative group. There were no statistically significant differences in 3- and 5-year DFS, OS, and DSS rates between the 2 groups. Five-year DFS was 92% vs 88% (hazard ratio [HR] 1.54 [0.56-4.27]; p = 0.404), 5-year OS was 94% vs 92% (HR 1.60 [0.49-5.26]; p = 0.441), and 5-year DSS was 94% vs 96% (HR 2.51 [0.46-13.71]; p = 0.290) for patients with and without adenomyosis, respectively. Conclusions: Coexistent adenomyosis in EC is not a prognostic factor and does not impact survival outcomes.

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