Is aromatase cytochrome P450 involved in the pathogenesis of endometrioid endometrial cancer?

2005 ◽  
Vol 15 (3) ◽  
pp. 529-536 ◽  
Author(s):  
V. H. W. M. Jongen ◽  
J. H. H. Thijssen ◽  
H. Hollema ◽  
G. H. Donker ◽  
J. G. Santema ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Body Fat ◽  
Venous Blood ◽  
Endometrial Tissue ◽  
Aromatase Activity ◽  
Fat Tissue ◽  
Water Release ◽  
Tissue Samples ◽  
Venous Circulation ◽  
Endometrioid Endometrial Cancer

Prospectively, the relationship between androgen levels in the utero-ovarian circulation, aromatase activity in endometrial and body fat tissue, and the presence or absence of endometrioid endometrial cancer was studied in postmenopausal women. In 43 women with endometrioid endometrial cancer and 8 women with a benign gynecological condition, a hysterectomy with bilateral salpingo-oophorectomy was performed. Using tritium water-release assays, aromatase activities in endometrial and body fat tissue were determined and related to the steroid levels from the peripheral and the utero-ovarian venous circulation (estradiol, androstenedione, testosterone) and to the presence or absence of endometrial cancer. Significant aromatase activity was found in both benign and malignant endometrial tissue samples. Aromatase activity in samples of endometrial tissue and in samples of body fat did not correlate with steroid levels in peripheral or utero-ovarian venous blood. Aromatase activity in samples of benign or malignant endometrium did not differ. Remarkably, in four women with mainly poorly differentiated endometrial cancer, very high aromatase activity was found in endometrial tissue. It is likely that multiple pathogenetic pathways exist that eventually lead to the formation of endometrioid endometrial cancer. The local availability of androgens and the finding that aromatase activity is present in both endometrial cancer and benign endometrial tissue support the hypothesis that aromatase activity in the endometrium may play a role in malignant transformation by converting androgens into mitogenic estrogens in the endometrial tissue.

scholarly journals Lipidomic Biomarkers in Polycystic Ovary Syndrome and Endometrial Cancer

2020 ◽  
Vol 21 (13) ◽  
pp. 4753 ◽  
Author(s):  
Mohamad Nasir Shafiee ◽  
Catharine A. Ortori ◽  
David A. Barrett ◽  
Nigel P. Mongan ◽  
Jafaru Abu ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Polycystic Ovary Syndrome ◽  
Molecular Mechanisms ◽  
High Resolution Mass Spectrometry ◽  
Polycystic Ovary ◽  
Capric Acid ◽  
Endometrial Tissue ◽  
University Hospital ◽  
Ovary Syndrome ◽  
Tissue Samples

Women with polycystic ovary syndrome (PCOS) are more likely to develop endometrial cancer (EC). The molecular mechanisms which increase the risk of EC in PCOS are unclear. Derangements in lipid metabolism are associated with EC, but there have been no studies, investigating if this might increase the risk of EC in PCOS. This was a cross-sectional study of 102 women in three groups of 34 (PCOS, EC and controls) at Nottingham University Hospital, UK. All participants had clinical assessments, followed by obtaining plasma and endometrial tissue samples. Lipidomic analyses were performed using liquid chromatography (LC) coupled with high resolution mass spectrometry (HRMS) and the obtained lipid datasets were screened using standard software and databases. Using multivariate data analysis, there were no common markers found for EC and PCOS. However, on univariate analyses, both PCOS and EC endometrial tissue samples showed a significant decrease in monoacylglycerol 24:0 and capric acid compared to controls. Further studies are required to validate these findings and investigate the potential role of monoacylglycerol 24:0 and capric acid in the link between PCOS with EC.

scholarly journals Integrated Analysis of Microbiome and Transcriptome Data Reveals the Interplay Between Commensal Bacteria and Fibrin Degradation in Endometrial Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Chao Li ◽  
Ye Gu ◽  
Qizhi He ◽  
Jian Huang ◽  
Yunfeng Song ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Degradation Products ◽  
Elevated Serum ◽  
Tumor Burden ◽  
High Serum ◽  
Endometrial Tissue ◽  
Integrated Analysis ◽  
Tissue Samples ◽  
Hematological Indicators ◽  
The Impact

The gut-uterus axis plays a pivotal role in the pathogenesis of endometrial cancer (EC). However, the correlations between the endometrial microbiome and endometrial tumor transcriptome in patients with EC and the impact of the endometrial microbiota on hematological indicators have not been thoroughly clarified. In this prospective study, endometrial tissue samples collected from EC patients (n = 30) and healthy volunteers (n = 10) were subjected to 16S rRNA sequencing of the microbiome. The 30 paired tumor and adjacent nontumor endometrial tissues from the EC group were subjected to RNAseq. We found that Pelomonas and Prevotella were enriched in the EC group with a high tumor burden. By integrating the microbiome and hematological indicators, a correlation was observed between Prevotella and elevated serum D-dimer (DD) and fibrin degradation products (FDPs). Further transcriptome analysis identified 8 robust associations between Prevotella and fibrin degradation-related genes expressed within ECs. Finally, the microbial marker of Prevotella along with DD and FDPs showed a high potential to predict the onset of EC (AUC = 0.86). Our results suggest that the increasing abundance of Prevotella in endometrial tissue combined with high serum DD and FDP contents may be important factors associated with tumor burden. The microbe-associated transcripts of host tumors can partly explain how Prevotella promotes DD and FDPs.

scholarly journals Evaluation of the Differences in the Expression of Biogenic Amine-Related mRNAs and Proteins in Endometrioid Endometrial Cancer

2021 ◽  
Vol 10 (21) ◽  
pp. 4872
Author(s):  
Michał Czerwiński ◽  
Anna Bednarska-Czerwińska ◽  
Nikola Zmarzły ◽  
Dariusz Boroń ◽  
Marcin Oplawski ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Biogenic Amine ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Histamine H4 Receptor ◽  
Tissue Samples ◽  
Protein Levels ◽  
Endometrioid Endometrial Cancer ◽  
H4 Receptor ◽  
Dopamine D5 Receptor

Biogenic amines, such as adrenaline, noradrenaline, histamine, dopamine, and serotonin are important neurotransmitters that also regulate cell viability. Their detection and analysis are helpful in the diagnosis of many diseases, including cancer. The aim of this study was to determine the expression profile of the biogenic amine-related genes and proteins in endometrioid endometrial cancer compared to the control group. The material consisted of endometrial tissue samples and whole blood collected from 30 endometrioid endometrial cancer patients and 30 cancer-free patients. The gene expression was determined by the mRNA microarrays and validated by qRT-PCR. Protein levels were determined in the serum by the enzyme-linked immunosorbent assay (ELISA). Overexpression of histamine H1–H3 receptors and early growth response 1 and silencing of calmodulin, the histamine H4 receptor, and the dopamine D5 receptor have been reported in endometrioid endometrial cancer. The obtained results indicate disturbances in the signaling activated by histamine and dopamine receptors, which could potentially contribute to the progression of endometrioid endometrial cancer.

scholarly journals The difference in histological grades of endometrial carcinoma in curettage and hysterectomy – cross-sectional study

2020 ◽  
Vol 56 (1) ◽  
pp. 36-44
Author(s):  
Barbara Sabrine Franjić ◽  
Iva Milić Vranješ ◽  
Jakov Milić ◽  
Milanka Mrčela
Keyword(s):  
Endometrial Cancer ◽  
Endometrial Carcinoma ◽  
Histological Grade ◽  
Tumor Grade ◽  
Analysis Data ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
Tissue Samples ◽  
Significant Difference ◽  
Endometrioid Endometrial Cancer

Objectives: To determine the compatibility rate between histological grades of endometrial carcinoma in curettage and hysterectomy and to determine how quantity of material, given by the method of fractional hysterectomy, affects the compatibility between histological grades in the two methods. Material and methods: The study included 102 patients with endometrioid endometrial cancer who underwent methods of fractional curettage and hysterectomy. Data regardingthepathohistological status of uterine tissue was obtained from the available medical records. Information on age andclinical diagnoses were obtained from referrals for pathohistologicaltissue examination. The age of the subjects was determined at the time when the tissue samples were taken for analysis. Data on the amount of material was obtained from the description of macroscopic evaluation of the given material. Results: Most subjects had grade II endometrioid endometrial cancer (47.1 % and 50 %). Most of the respondents had a medium deficient material obtained by fractional curettage (40.2 %). There was no statistically significant difference between the histological grade determined after the fractional curettage and hysterectomy. There were no statistically significant differences in histological grade in the sample obtained by fractional curettage and hysterectomy depending on the amount of material in fractional curettage. Conclusions: There was no statistically significant differences in the grade of endometrial cancer in samples obtained by the fractional curettage and hysterectomy. The correspondence is higher in higher tumor grade (III), and lower in lower tumor grades (I, II). The amount of material did not affect the grade deviation in the sample obtained by fractional curettage and hysterectomy.

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.

scholarly journals Metabolomic Biomarkers for the Detection of Obesity-Driven Endometrial Cancer

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 718
Author(s):  
Kelechi Njoku ◽  
Amy E. Campbell ◽  
Bethany Geary ◽  
Michelle L. MacKintosh ◽  
Abigail E. Derbyshire ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Early Detection ◽  
Minimally Invasive ◽  
Cancer Detection ◽  
Test Performance ◽  
Female Genital Tract ◽  
Screening Tools ◽  
Normal Endometrium ◽  
Endometrioid Endometrial Cancer ◽  
Post Menopausal

Endometrial cancer is the most common malignancy of the female genital tract and a major cause of morbidity and mortality in women. Early detection is key to ensuring good outcomes but a lack of minimally invasive screening tools is a significant barrier. Most endometrial cancers are obesity-driven and develop in the context of severe metabolomic dysfunction. Blood-derived metabolites may therefore provide clinically relevant biomarkers for endometrial cancer detection. In this study, we analysed plasma samples of women with body mass index (BMI) ≥ 30 kg/m2 and endometrioid endometrial cancer (cases, n = 67) or histologically normal endometrium (controls, n = 69), using a mass spectrometry-based metabolomics approach. Eighty percent of the samples were randomly selected to serve as a training set and the remaining 20% were used to qualify test performance. Robust predictive models (AUC > 0.9) for endometrial cancer detection based on artificial intelligence algorithms were developed and validated. Phospholipids were of significance as biomarkers of endometrial cancer, with sphingolipids (sphingomyelins) discriminatory in post-menopausal women. An algorithm combining the top ten performing metabolites showed 92.6% prediction accuracy (AUC of 0.95) for endometrial cancer detection. These results suggest that a simple blood test could enable the early detection of endometrial cancer and provide the basis for a minimally invasive screening tool for women with a BMI ≥ 30 kg/m2.

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