scholarly journals Prognostic classification of endometrial cancer using a molecular approach based on a twelve-gene NGS panel

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Raquel López-Reig ◽  
Antonio Fernández-Serra ◽  
Ignacio Romero ◽  
Cristina Zorrero ◽  
Carmen Illueca ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Copy Number ◽  
Disease Free Survival ◽  
Developed Countries ◽  
Molecular Techniques ◽  
The Cancer Genome Atlas ◽  
Molecular Approach ◽  
Random Forest Classification ◽  
Forest Classification ◽  
Prognostic Groups

AbstractEndometrial Cancer (EC) is one of the most common malignancies in women in developed countries. Molecular characterization of different biotypes may improve clinical management of EC. The Cancer Genome Atlas (TCGA) project has revealed four prognostic EC subgroups: POLE, MSI; Copy Number Low (CNL) and Copy Number High (CNH). The goal of this study was to develop a method to classify tumors in any of the four EC prognostic groups using affordable molecular techniques. Ninety-six Formalin-Fixed Paraffin-embedded (FFPE) samples were sequenced following a NGS TruSeq Custom Amplicon low input (Illumina) protocol interrogating a multi-gene panel. MSI analysis was performed by fragment analysis using eight specific microsatellite markers. A Random Forest classification algorithm (RFA), considering NGS results, was developed to stratify EC patients into different prognostic groups. Our approach correctly classifies the EC patients into the four TCGA prognostic biotypes. The RFA assigned the samples to the CNH and CNL groups with an accuracy of 0.9753 (p < 0.001). The prognostic value of these groups was prospectively reproduced on our series both for Disease-Free Survival (p = 0.004) and Overall Survival (p = 0.030).Hence, with the molecular approach herein described, a precise and suitable tool that mimics the prognostic EC subtypes has been solved and validated. Procedure that might be introduced into routine diagnostic practices.

scholarly journals Mismatch repair deficiency: a step forward personalized medicine in endometrial cancer?

2016 ◽  
Vol 4 (2) ◽  
pp. 34-41
Author(s):  
Chiara Della Pepa ◽  
Susana Banerjee ◽  
Angela George
Keyword(s):  
Endometrial Cancer ◽  
Copy Number ◽  
Current Knowledge ◽  
Prognostic Significance ◽  
Good Prognosis ◽  
The Cancer Genome Atlas ◽  
Therapeutic Implications ◽  
Repair Deficiency ◽  
Cancer Genome Atlas

Endometrial cancer (EC) is the most common female malignancy in the world, it has traditionally been classified into two subgroups based on histopathological features, however this dualistic classification does not take into consideration subtypes such as high-grade endometrioid EC. Recently, work performed as part of The Cancer Genome Atlas study has focused on molecular genomic classification of EC, with four distinct molecular subtypes described: 1. POLE ultramutated, associated with a good prognosis; 2. Microsatellite instability (MSI) hypermutated; 3. Copy number low and microsatellite stable; 4. Copy number high, serous like, associated with a poor prognosis. The subgroup of patients with MSI is of particular interest for a number of reasons, including the use of tumour screening to identify patients with Lynch syndrome, the prognostic significance of MSI, and the potential therapeutic implications. This review will focus on the current knowledge in these areas and potential future directions.

scholarly journals Hypermethylated PCDHGB7 as a Biomarker for Early Detection of Endometrial Cancer in Endometrial Brush Samples and Cervical Scrapings

2022 ◽  
Vol 8 ◽  
Author(s):  
Jiangjing Yuan ◽  
Zhanrui Mao ◽  
Qi Lu ◽  
Peng Xu ◽  
Chengyang Wang ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Early Detection ◽  
Minimally Invasive ◽  
Predictive Value ◽  
Developed Countries ◽  
The Cancer Genome Atlas ◽  
Clinical Samples ◽  
Data Sets ◽  
Methylation Marker ◽  
Validation Set

Endometrial cancer (EC) is one of the most common gynecologic cancers in developed countries. Presently, it is imperative to develop a reliable, noninvasive, or minimally invasive detection method for EC. We explored the possibility of using DNA methylation marker from endometrial brush samples (with a “Tao brush”) and cervical scrapes (with a “Pap brush”) for early detection of EC. We analyzed the methylation data of EC and normal endometrial tissues from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) data sets. An optimized methylation-sensitive restriction enzyme combined with real-time fluorescent quantitative PCR (MSRE-qPCR) was used for methylation detection. Included in the training set were 143 endometrial tissues, 103 Tao, and 109 Pap brush samples. The validation set included 110 Tao and 112 Pap brush samples. PCDHGB7 was significantly hypermethylated in EC compared with normal endometrial tissues in the TCGA and GEO data sets (AUC &gt;0.95), which was verified in clinical samples. In the Pap brush samples, the AUC was 0.86 with 80.65% sensitivity and 82.81% specificity, whereas the Tao brush samples exhibited higher specificity (95.31%). The combination of Tao and Pap brush samples significantly increased the sensitivity to 90.32%. In the validation set, the final model yielded a sensitivity of 98.61%, specificity of 60.53%, positive predictive value of 82.56%, and negative predictive value of 95.83%. These results demonstrate the potential application of the novel methylation marker, hypermethylated PCDHGB7, in cervical scrapings and endometrial brush, which provides a viable, noninvasive, or minimally invasive method for early endometrial cancer detection across different clinical features and histologies to supplement current hysteroscopy diagnosis.

scholarly journals AKR1C3 Is Associated with Better Survival of Patients with Endometrial Carcinomas

2020 ◽  
Vol 9 (12) ◽  
pp. 4105
Author(s):  
Marko Hojnik ◽  
Nataša Kenda Šuster ◽  
Špela Smrkolj ◽  
Snježana Frković Grazio ◽  
Ivan Verdenik ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Endometrial Cancer ◽  
Confidence Interval ◽  
Disease Free Survival ◽  
Predictive Biomarkers ◽  
Developed Countries ◽  
Hazard Ratio ◽  
Free Survival ◽  
Response To Chemotherapy ◽  
Disease Free

The aldo-keto reductase (AKR) superfamily is gaining attention in cancer research. AKRs are involved in important biochemical processes and have crucial roles in carcinogenesis and chemoresistance. The enzyme AKR1C3 has many functions, which include production of prostaglandins, androgens and estrogens, and metabolism of different chemotherapeutics; AKR1C3 is thus implicated in the pathophysiology of different cancers. Endometrial and ovarian cancers represent the majority of gynecological malignancies in developed countries. Personalized treatments for these cancers depend on identification of prognostic and predictive biomarkers that allow stratification of patients. In this study, we evaluated the immunohistochemical (IHC) staining of AKR1C3 in 123 paraffin-embedded samples of endometrial cancer and 99 samples of ovarian cancer, and examined possible correlations between expression of AKR1C3 and other clinicopathological data. The IHC expression of AKR1C3 was higher in endometrial cancer compared to ovarian cancer. In endometrioid endometrial carcinoma, high AKR1C3 IHC expression correlated with better overall survival (hazard ratio, 0.19; 95% confidence interval, 0.06−0.65, p = 0.008) and with disease-free survival (hazard ratio, 0.328; 95% confidence interval, 0.12–0.88, p = 0.027). In patients with ovarian cancer, there was no correlation between AKR1C3 IHC expression and overall and disease-free survival or response to chemotherapy. These results demonstrate that AKR1C3 is a potential prognostic biomarker for endometrioid endometrial cancer.

scholarly journals The Oncology Safety of Diagnostic Hysteroscopy in Early-Stage Endometrial Cancer: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Yi Du ◽  
Yu Xu ◽  
Zhaojuan Qin ◽  
Liang Sun ◽  
Yali Chen ◽  
...  
Keyword(s):  
Systematic Review ◽  
Endometrial Cancer ◽  
Early Stage ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Developed Countries ◽  
Cochrane Library ◽  
Cancer Disease ◽  
Oncological Safety ◽  
Early Stage Endometrial Cancer

BackgroundHysteroscopy is becoming a common method for the diagnosis of uterine disorders in developed countries. However, hysteroscopy might worsen the prognosis of endometrial cancer because it could cause cancer dissemination into the peritoneal cavity through the fallopian tubes. Objective: The aim of this systematic review and meta-analysis was to explore the oncological safety of hysteroscopy for early-stage endometrial cancer.Search StrategyEligible studies were obtained from PubMed, Embase, and the Cochrane Library up to September 22, 2020.Selection CriteriaStudies which compared the oncological safety of hysteroscopy with other methods were included.Data Collection and AnalysisA total of 3980 patients were included in this study, of whom1357 patients had undergone hysteroscopy and2623 had not.Main ResultsThere was no significant association between hysteroscopy and worse prognosis in early-stage endometrial cancer [disease-free survival: log risk ratio(logRR) -0.22; 95% confidence interval (CI), -0.54 to 0.1; p=0.97; overall survival: logRR 0.03; 95% CI, -0.05 to 0.11; p=0.02; disease-specific survival: logRR 0.03; 95% CI, -0.03 to 0.10; p=0.00].ConclusionThis study suggests that hysteroscopy is a safe diagnostic and treatment method, and has no significant effect on the prognosis of early-stage endometrial cancer.Systematic Review RegistrationPROSPERO registration number: CRD42020193696.

scholarly journals Does an Endometrial Cancer Diagnosis among Asymptomatic Patients Improve Prognosis?

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 115
Author(s):  
Petra Vinklerová ◽  
Petra Ovesná ◽  
Markéta Bednaříková ◽  
Luboš Minář ◽  
Michal Felsinger ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Cancer Patients ◽  
Statistical Significance ◽  
Multivariable Analysis ◽  
Disease Free Survival ◽  
Developed Countries ◽  
Gynecological Malignancy ◽  
European Guidelines ◽  
Preclinical Phase ◽  
Asymptomatic Patients

Background: Endometrial cancer is the most common gynecological malignancy in developed countries with no screening available. There is still a tendency to provide invasive bioptic verification in asymptomatic women with abnormal ultrasound findings to diagnose carcinoma in a preclinical phase; even though, it is not supported by European guidelines. Our goal was to determine DFS (disease-free survival), OS (overall survival), and DSS (disease-specific survival) differences between symptom-free and symptomatic (bleeding, or spotting) endometrial cancer patients with similar stage and tumor/clinical characteristics. Methods: All of our patients with endometrial cancer following surgical treatment between 2006 and 2019 were assessed, evaluating risk factors for recurrence and death while focusing on bleeding using univariable and multivariable analysis. Results: 625 patients meeting the inclusion criteria were divided into asymptomatic (n = 144, 23%) and symptomatic (n = 481, 77%) groups. The median follow-up was 3.6 years. Using univariable analysis, symptomatic patients had a three times higher risk of recurrence (HR 3.1 (95% Cl 1.24–7.77), p = 0.016). OS (HR 1.35 (0.84–2.19), p = 0.219) and DSS (HR 1.66 (0.64–4.28), p = 0.3) were slightly worse without reaching statistical significance. In our multivariable analysis, symptomatology was deemed completely insignificant in all monitored parameters (DFS: HR 2.03 (0.79–5.24), p = 0.144; OS: HR 0.72 (0.43–1.21), p = 0.216). Conclusions: The symptomatic endometrial cancer patients risk factor of earlier recurrence and death is insignificantly higher when compared with the asymptomatic cohort. However, multivariable analysis verifies that prognosis worsens with other clinically relevant parameters, not by symptomatology itself. In terms of survival outcome in EC patients, we recognized symptomatology as a non-significant marker for the patient’s prognosis.

scholarly journals Adjuvant Treatment Recommendations in Early-Stage Endometrial Cancer: What Changes With the Introduction of The Integrated Molecular-Based Risk Assessment

2021 ◽  
Vol 11 ◽  
Author(s):  
Camilla Nero ◽  
Francesca Ciccarone ◽  
Antonella Pietragalla ◽  
Simona Duranti ◽  
Gennaro Daniele ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Endometrial Cancer ◽  
Adjuvant Therapy ◽  
Copy Number ◽  
Early Stage ◽  
Tumor Grade ◽  
Risk Groups ◽  
Molecular Classification ◽  
The Cancer Genome Atlas ◽  
Histologic Subtype

Adjuvant therapy recommendations for endometrial cancer were historically based on the individual patient’s risk of disease recurrence using clinicopathologic factors such as age, stage, histologic subtype, tumor grade, and lymphovascular space invasion. Despite the excellent prognosis for early stages, considerable under- and overtreatment remains. Integrated genomic characterization by the Cancer Genome Atlas (TCGA) in 2013 defined four distinct endometrial cancer subgroups (POLE mutated, microsatellite instability, low copy number, and high copy number) with possible prognostic value. The validation of surrogate markers (p53, Mismatch repair deficiency, and POLE) to determine these subgroups and the addition of other molecular prognosticators (CTNNB1, L1CAM) resulted in a practical and clinically useful molecular classification tool. The incorporation of such molecular alterations into established clinicopathologic risk factors resulted in a refined, improved risk assessment. Thus, the ESGO/ESTRO/ESP consensus in 2020 defined for the first time different prognostic risk groups integrating molecular markers. Finally, the feasibility and clinical utility of molecular profiling for tailoring adjuvant therapy in the high-intermediate-risk group is currently under investigation (NCT03469674).

Sarginio limfmazgio nustatymas sergant endometriumo vėžiu: nauja chirurginio stadijavimo kryptis

2020 ◽  
Vol 23 (1) ◽  
Author(s):  
Linas Andreika ◽  
Margarita Montrimaitė ◽  
Juliana Andreičik
Keyword(s):  
Endometrial Cancer ◽  
Lymph Node ◽  
Sentinel Lymph Node ◽  
Sentinel Lymph Node Biopsy ◽  
Gynecological Cancer ◽  
Developed Countries ◽  
Lymph Node Biopsy ◽  
Sentinel Lymph Nodes ◽  
Cancer Management ◽  
Node Biopsy

Summary. Endometrial cancer is the most common gynecological cancer in developed countries. Biopsy of the sentinel lymph node can be considered as an alternative to full lymphadenectomy. In order to identify sentinel lymph nodes, a tracer substance is injected into the uterus to visualize the lymphatic tract. Commonly used tracer substances are Technetium-99m (99mTc) colloid, blue dyes, and indocyanine green (ICG). In this review the significance of sentinel lymph node biopsy in endometrial cancer management and the technique of the procedure is discussed.

Lynch syndrome-related non-endometrioid endometrial cancer: analysis of outcomes

2019 ◽  
Vol 30 (1) ◽  
pp. 56-61
Author(s):  
Giorgio Bogani ◽  
Maria Grazia Tibiletti ◽  
Maria Teresa Ricci ◽  
Ileana Carnevali ◽  
Viola Liberale ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Lynch Syndrome ◽  
Disease Free Survival ◽  
Oncologic Outcomes ◽  
Cox Models ◽  
Matching Algorithm ◽  
Pathogenic Variants ◽  
Propensity Matching ◽  
Endometrioid Endometrial Cancer

ObjectiveWomen with Lynch syndrome have a risk up to 40–60% of developing endometrial cancer, which is higher than their risk of developing colorectal or ovarian cancer. To date, no data on the outcomes of patients with Lynch syndrome diagnosed with non-endometrioid endometrial cancer are available. The goal of this study was to evaluate the outcome of patients with Lynch syndrome diagnosed with non-endometrioid endometrial cancer.MethodsData from consecutive patients diagnosed with Lynch syndrome and with a histological diagnosis of non-endometrioid endometrial cancer were retrospectively collected in two referral institutes in Italy. A case–control comparison (applying a propensity matching algorithm) was performed in order to compare patients with proven Lynch syndrome and controls. Inclusion criteria were: (a) histologically-proven endometrial cancer; (b) detection of a germline pathogenic variant in one of the MMR genes; (c) adequate follow-up. Only carriers of pathogenic or likely pathogenic variants (ie, class 5 and 4 according to the InSiGHT classification) were included in the study. Survival outcomes were assessed using KaplanMeier and Cox models.ResultsOverall, 137 patients with Lynch syndrome were collected. Mean patient age was 49.2 (10.9) years. Genes involved in the Lynch syndrome included MLH1, MSH2, and MSH6 in 43%, 39%, and 18% of cases, respectively. The study population included 27 patients with non-endometrioid endometrial cancer, who were matched 1:2 with patients with sporadic cancers using a propensity matching algorithm. After a median follow-up of 134 months (range 1–295), 2 (7.4%) of the 27 patients developed recurrent disease (3 and 36 months) and subsequently died of disease (7 and 91 months). Patients diagnosed with Lynch syndrome experienced better disease-free survival (HR 7.86 (95% CI 1.79 to 34.5); p=0.006) and overall survival (HR 5.33 (95% CI 1.18 to 23.9); p=0.029) than controls.ConclusionsNon-endometrioid endometrial cancer occurring in patients with Lynch syndrome might be associated with improved oncologic outcomes compared with controls. Genetic/molecular profiling should be investigated in order to better understand the mechanism underlying the prognosis.

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