Features Of Endometrial Cancer Research Articles

Integrative Analysis of Multi-Omic Data for the Characteristics of Endometrial Cancer.

Endometrial cancer (EC) is a frequently diagnosed gynecologic cancer. Identifying reliable prognostic genes for predicting EC onset is crucial for reducing patient morbidity and mortality. Here, a comprehensive strategy with transcriptomic and proteomic data was performed to measure EC's characteristics. Based on the publicly available RNA-seq data, death-associated protein kinase 3, recombination signal-binding protein for the immunoglobulin kappa J region, and myosin light chain 9 were screened out as potential biomarkers that affect the EC patients' prognosis. A linear model was further constructed by multivariate Cox regression for the prediction of the risk of being malignant. From further integrative analysis, exosomes were found to have a highly enriched role that might participate in EC occurrence. The findings were validated by qRT-polymerase chain reaction (PCR) and western blotting. Collectively, we constructed a prognostic-gene-based model for EC prediction and found that exosomes participate in EC incidents, revealing significantly promising support for the diagnosis of EC.

Recurrence and characteristics of endometrial cancer in elderly patients

Aim: In this study, evaluated the treatment options of patients of advanced age (≥70 years) with recurrence, survival results were analyzed. Methods: The data of patients diagnosed with endometrial cancer (EC) in the Gynecological Oncology Clinic between 2001 and 2020 were evaluated retrospectively. Seventy six cases with advanced age and relapse were evaluated. Patients who underwent hysterectomy surgery in our center and continued their follow-up regularly were included in the study. Results: The mean age at the time of recurrence was 74.6 ± 3.9 years. The endometrioid type, seen in half of the patients, was the most common histological type. Pelvic paraaortic lymph node (LN) sampling/dissection was performed in 84.2% of the patients. Deep myometrial invasion was detected in 56 (73.7%) patients, and LVSI was found in 42 (56.8%) patients. The mean time to recurrence was found to be 25.1 ± 17.8 months. Total survival times were calculated as 47.2 ± 28.2 months. The five-year overall survival (OS) rate was analyzed as 35.7%. The most common site of recurrence was lung, and isolated lung recurrence was seen in 14 (18.5%) patients. There was no significant difference for OS among patients with pelvic recurrence and extra-pelvic/multiple recurrences (P= 0.723). Conclusion: Survival outcomes in recurrences are worse in advanced age endometrial cancer patients. This may be due to more limited treatment options for recurrence due to additional internal problems.

Association of the Duffy-null allele and endometrial cancer characteristics: An effort to explore racial disparity in Black women with endometrial cancer.

5603 Background: Efforts are needed to identify factors that account for the disparately high mortality in Black women with endometrial cancer. The Duffy antigen receptor for chemokines (DARC) is expressed on erythrocytes and endothelial cells and modulates levels of inflammatory chemokines in circulation and in tissues. The African ancestry-specific Duffy-null allele, in which erythrocyte expression and function of DARC is lost, is associated with worse breast cancer phenotypes and survival. Here, we characterize Duffy-null status and associated prognostic and clinical outcomes in patients with endometrial cancer. Methods: Patients with endometrial cancer were prospectively consented, and germline DNA was extracted from saliva or blood samples. Duffy-null genotype was determined using an allelic discrimination assay. Associations between Duffy-null genotype status and clinicopathologic characteristics were performed using Fisher’s Exact analysis. Results: 33 patients were enrolled (Table); 17 (51.5%) were Duffy-null, 5 (15.2%) were Duffy-null allele carriers, and 11 (33.3%) were non-carriers. Compared with non-carriers, Duffy-null patients were more likely to be Black (100% v 9.1%, p<0.0001) and have non-endometrioid histology (64.7% v 10%, p=0.0173). There was a trend towards higher rates of grade 3 histology (70.6% v 36.6%), intact tumor mismatch repair (MMR) (86.7% v 54.6%), estrogen receptor (ER) negative tumor status (25% v 10%), advanced stage (37.5% v 18.2%), and positive lymph nodes (25% v 0%) (Table). Over a minimum of 12 months of follow up, only Duffy-null individuals died from disease (4 v 0, p=0.0006). Conclusions: Duffy-null status was associated Black race, aggressive histologic subtypes, intact MMR mechanisms, and worse survival. Further investigation is needed to explore the underlying mechanism of the Duffy-null phenotype on endometrial cancer outcomes to better elucidate risk factors and underlying causes that may contribute to endometrial cancer disparities.[Table: see text]

Endometrial Cancer Characteristics and Risk of Recurrence.

To describe clinicopathologic characteristics and survival outcomes of endometrial adenocarcinomas stratified by mismatch repair (MMR) status. Single-institution, retrospective study of all women with endometrioid adenocarcinomas treated from January 2012 through December 2017. Patients were categorized into one of three groups based on MMR testing: intact MMR expression (MMR+), probable MMR mutation (MMR-), or MLH1 hypermethylation (hMLH1+). Demographics, pathologic characteristics, recurrence rates, and survival differences were analyzed. In total, 316 women were included in the analysis: 235 (74.4%) patients in the MMR+ group, 10 (3.1%) in the MMR- group, and 71 (22.5%) in the hMLH1+ group. Patients with hMLH1+ were significantly older, exhibited higher-grade histology and presence of lymphovascular space invasion, and were more likely to have received adjuvant treatment. The early stage hMLH1+ patients were more likely to recur (15.3% hMLH1+ vs 2.3% MMR+ vs 12.5% MMR-, P < .001). Hypermethylation remained a significant predictor of recurrence in multivariable analysis (odds ratio, 5.09; 95% confidence interval [CI], 1.54-16.86; P = .008). Recurrence-free survival was significantly reduced in early stage hMLH1+ (hazard ratio, 7.40; 95% CI, 2.80-21.62; P < .001). Women with hMLH1+ endometrial cancer have worse prognostic features and recur more frequently, even in patients traditionally considered low risk for recurrence.

Genomic characteristics of endometrial cancer in China.

e17569 Background: Molecular classification of endometrial cancer has been applied in patient stratification and treatment strategy. Although the Cancer Genome Atlas project and other genomic studies have established comprehensive molecular classification, its genomic characteristics in Chinese endometrial cancer remain unclear. Methods: Tumor tissue and matched white blood cells from 316 patients with endometrial cancer underwent next-generation sequencing (NGS), which targeted the whole coding region of 733 or 381 genes. Endometrial cancer was classified into four subtypes according to genomic characteristics: polymerase (POLE) ultramutated, microsatellite instability (MSI), TP53 wild type (TP53wt), and TP53 mutant (TP53mut). Tumor mutation burden (TMB) was calculated based on the number of somatic single nucleotide variants and indels in examined coding regions. Deleterious or suspected deleterious genes were included for analysis. Genomic instability was also evaluated with Homologous Recombination Deficiency (HRD) score by over 10, 000 single-nucleotide polymorphisms distributed across human genome. HRD algorithm combined loss of heterozygosity score (LOH), telomeric allelic imbalance score (TAI) and large-scale state transition score (LST). Results: The 316 endometrial cancer patients were divided into four subtypes: POLE ultramutated (16, 5.06%), MSI tumors (70, 22.2%), TP53wt (131, 41.5%), and TP53mut (99, 31.3%). Median TMB was 26.5 mut/Mb in overall cohort and POLE ultramutated subtype possessed the highest TMB (181 mut/Mb), followed by MSI (54.1 mut/Mb), TP53mut (7.11 mut/Mb) and TP53wt (6.61 mut/Mb) subtypes. POLE, PTEN, LRP1B, BRCA2 and ATRX were the top frequently mutated genes in POLE ultramutated subtype, which mutation rate are more that 80%. The most frequent mutations were detected in ARID1A, PTEN, PIK3CA in MSI subtype, TP53, PIK3CA, PTEN in TP53mut subtype, and PTEN, PIK3CA, ARID1A in TP53wt subtype. HRD score was significantly higher in TP53mut subtype, followed by TP53wt, MSI and POLE ultramutated subtype (median HRD score, 21.7, 6.15, 3.65 and 0; P &lt; 0.001). Conclusions: Our study revealed the heterogeneous genomic characteristics of four molecular subtypes in Chinese endometrial cancer. POLE ultramutated and MSI subtypes display higher TMB. TP53mut subtype showed genome features of HRD and would likely benefit from HRD-targeted therapy.

The clinical characteristics and prognosis of endometrial carcinomas that occur after breast cancer: does hormone receptor status of breast cancer matter?

To evaluate the clinical and pathological features of endometrial cancer (EC) following breast cancer and to assess the effect of the breast cancer hormone receptor status on subsequent EC. A retrospective study based on SEER data of EC patients with a history of breast cancer. A total of 2142 cases met the inclusion criteria. Compared to that of the general population, the incidence of EC following estrogen receptor-positive (ER+) breast cancer and hormone receptor-negative (HR-) breast cancer increased by approximately 16-fold and 15-fold, respectively. Histologically, the proportions of type II EC following ER+ breast cancer, HR- breast cancer and primary EC were 39.6%, 39.4% and 31.2%, respectively (P < 0.001). The proportions of G3 ECs were 26.9%, 28.2% and 19.8%, respectively (P < 0.001). The proportion of patients who died from miscellaneous malignant tumors among EC patients following breast cancer was significantly higher than the proportion of patients among primary ECs. The overall survival rate was worse for EC patients with a history of breast cancer (P < 0.001). There were no significant differences between patients with EC following ER+ breast cancer and those with EC following HR- breast cancer with regard to stage, lymphatic metastasis, outcome or cause of death. Compared to the general population, the incidence of EC in patients with breast cancer was increased markedly. Patients with EC following ER+ or HR- breast cancer shared the same clinicopathological features and prognoses. All patients need close monitoring regardless of breast cancer hormone receptor status.

Molecular and pathologic features of endometrial cancer in young patients

Molecular and pathologic features of endometrial cancer in young patients

Comparative analysis of the value of diffusion kurtosis imaging and diffusion-weighted imaging in evaluating the histological features of endometrial cancer

PurposeThis study evaluated and compared the performances of diffusion kurtosis imaging (DKI) and diffusion-weighted imaging (DWI) for diagnosing and histologically grading endometrial cancer.Materials and methodsIn this retrospective study, DKI and DWI data for 61 patients with endometrial cancer and 30 patients with a normal endometrium were analyzed, and the mean kurtosis (MK), mean diffusion coefficient (MD) and apparent diffusion coefficient (ADC) values for the endometrial cancer tissue and normal endometrial tissue were acquired. The parameters for the normal endometrium group (G0) and the endometrial cancer groups (G1, G2 and G3) were compared and analyzed. The receiver operating characteristic (ROC) curve was used to evaluate each parameter’s diagnostic accuracy and threshold. Spearman correlation analysis was used to analyze the correlations between all parameters and histological grades.ResultsThe MK values for the G0, G1, G2 and G3 groups increased gradually, while the MD and ADC values decreased gradually. Except for the differences in the ADC values between G0 and G1, the differences among the groups were statistically significant (P < 0.05). The MK values had the highest diagnostic accuracy in differentiating G0 and (G1 + G2 + G3), G0 and G1, G1 and G2, and G2 and G3 (AUC = 0.93, 0.76, 0.91, 0.91, P < 0.05). MK was maximally correlated with histological grade, followed by MD and ADC (MK > MD > ADC; r = − 0.85, + 0.82, + 0.76, P < 0.01).ConclusionBoth DKI and DWI can be used to evaluate the diagnosis and histological grading of endometrial cancer. Compared with DWI, the DKI model is a more complete mathematical model with more sensitive parameters, which can more effectively evaluate the pathological and physiological characteristics of endometrial cancer.

Molecular characteristics of endometrial cancer and their potential effect on clinical management

Molecular characteristics of endometrial cancer and their potential effect on clinical management

OC14.01: Ultrasound characteristics of endometrial cancer as defined by the International Endometrial Tumor Analysis (IETA) consensus nomenclature: a prospective multicentre study

OC14.01: Ultrasound characteristics of endometrial cancer as defined by the International Endometrial Tumor Analysis (IETA) consensus nomenclature: a prospective multicentre study

CHANGES IN ENDOMETRIAL CANCER CLINICAL AND MORPHOLOGICAL FEATURES DURING THE PAST HALF CENTURY

Objective of the study was to compare the characteristics of endometrial cancer (EC) in patients observed in years 1965 - 1969, 1995 - 1999 and 2012 - 2015. Results. The research was conducted on the basis of the same institution and it showed that over the past 50 years (1965 to 2015) an increase in the average age of women with primary EC. Despite the increase by through the decades in relatively favorable endometrial adenocarcinomas in relation to non-endometrioid tumors, with the increasing age of patients the incidence of non-endometrioid carcinomas increased especially due to women older than 60 years compared with patients younger than 50 years. This was reflected in such characteristics as stage of the process (according to FIGO), degree of tumor differentiation, proportion of serous carcinomas and expression of HER-2/neu. Conclusion. Taken into account contemporary renewal of molecular-biological classification of endometrial cancer types the data collected in this study may also have practical value in particular for decisions related to personalized conservative therapy options.

Clinico-pathological features of endometrial cancer in Lynch Syndrome patients in comparison with the general population

Clinico-pathological features of endometrial cancer in Lynch Syndrome patients in comparison with the general population

Features of endometrial cancer in patients with 'metabolically healthy' versus 'standard' obesity: the decreasing frequency of metabolically healthy obesity.

Background:As endometrial cancer (EC) prevalence increases with obesity, we aimed to determine whether EC characteristics depend upon obesity type: ‘standard’ (SO) or ‘metabolically healthy obesity’ (MHO).Patients & methods:258 EC patients were included. Data on anthropometry, blood hormones, lipids and glucose, and tumor features were collected.Results:EC clinicopathologic characteristics and clinical stage correlate differently with BMI and obesity type. BMI is related inversely with tumor grade while SO patients are characterized by a more advanced clinical stage than those with MHO. Besides typical insulin resistance signs, EC patients with SO often display a higher serum leptin/adiponectin ratio compared with MHO patients. Historical data suggest a gradual increase in EC patient height and weight, and a decrease in MHO prevalence.Conclusion:It is currently unknown whether the latter observation reflects the evolution of EC, or obesity alongside the current epidemic. Regardless, the reduced MHO prevalence demonstrates the need for more intensive preventive measures aimed at obesity and obesity-associated conditions, including different EC subtypes.

P0064 Investigation of endometrial cancer and associated risk factors at Lagos University Teaching Hospital, Nigeria: A 5-year review

Background Endometrial cancer is the most common gynaecological cancer in most developed countries. Although endometrial carcinoma is still the third commonest gynaecological malignancy in Nigeria, incidence is increasing. Endometrial cancer is most common among postmenopausal women and postmenopausal bleeding is the hallmark symptom. The main risk factors for the development of endometrial carcinoma are advanced age, menopause, and obesity. All women with suspected endometrial cancer require transvaginal ultrasonography and most will undergo endometrial biopsy; more sophisticated radiological examinations are required for accurate preoperative staging. We sought to determine the risk factors and clinical features of endometrial cancer in patients presenting between January, 2008, and December, 2012, at Lagos University Teaching Hospital. Methods This was a retrospective study done at Lagos University Teaching Hospital. All patients who had endometrial cancer during the trial period were identified and their case notes were retrieved from the medical records. Relevant data were obtained using a proforma. The data obtained were collated and analysed using simple tables and graphs. The identified risk factors, clinical features, and a diagnostic evaluation of women with endometrial cancer were compared with data published in the literature. Findings During the study period, the number of patients diagnosed with endometrial cancer was 61. However, only 44 (72%) whose case notes were retrieved were studied; 17 (28%) patients whose case folders were not found were excluded. Endometrial cancer was uncommon in young and premenopausal women as it was found in only one (2%) woman younger than 40 years. The malignancy occurred in 25 (41%) women of middle age (41–60 years) and in 35 (57%) older women (> 60 years). Of the women diagnosed, eight (18%) were premenopausal and 36 (82%) were postmenopausal. The predominant complaint was postmenopausal vaginal bleeding, which was reported by all the women. The most common risk factors were old age, overweight, and obesity. The most common subtype was the endometrioid type. Interpretation The major risk factors for endometrial cancer in this hospital setting in Nigeria include advanced age, menopause, overweight, and obesity. While findings in ultrasonography could be suggestive of the disease, endometrial biopsy is diagnostic.

Genetic Polymorphism of PRKCDBP is Associated with an Increased Risk of Endometrial Cancer

PRKCDBP is a putative tumor suppressor located at 11p15.4, where frequent genomic loss has been observed in human cancers. We explored the possible association between an intra-exonic single nucleotide polymorphism (SNP), rs1051992, that results in a Leu to Pro substitution, and risk for endometrial carcinogenesis. We assessed the genotype of rs1051992 in endometrial cancer tissues from 147 patients and normal endometrial tissue from 191 healthy individuals by restriction endonuclease PvuII-based genotyping. Allele frequencies in the cancer specimens were compared with those in the healthy controls. We also evaluated the association between polymorphisms at this locus and histopathological features of endometrial cancer.

Endometrial carcinoma in the Baby Boomer generation: Tumor characteristics and clinical outcome.

e15512 Background: Baby Boomers (BB) enterring retirement are representing a significant burden on medical resources. The unique lifestyle characteristics engendered by the BB may lead to different endometrial cancer characteristics that bear understanding. We sought to characterize surgically staged BB patients with endometrioid carcinoma and compare the results to pre-Boomers (PB) patients. Methods: After reviewing our database of 1,450 patients with endometrial cancer, we identified 595 patients with 2009 FIGO stage I-II uterine endometrioid carcinoma who were born between 1926 and 1964. Their medical records were reviewed in this IRB-approved study. Patients with non-endometrioid carcinoma and those received preoperative therapy or chemotherapy were excluded. Patients were defined as BB (born 1946-1964) or PB (born in 1926-1945). The two groups were compared regarding patient’s demographics, tumor characteristics and survival. Results: All patients were surgically staged with a minimum of two years follow-up.BB group included 234 patients (39%) and PB with 361 patients (61%).Median follow-up for the study cohort was 72 months. Baby boomers had higher BMI (p=0.027), younger age at diagnosis (p=0.002), lower tumor grade (p=0.002), earlier FIGO stage (p=0.023), higher number of lymph dissected (p=0.008), less lymphovascular space involvement (LVSI) (p=&lt;0.034), and less frequent utilization of adjuvant therapy (p=&lt;0.001). However, there was no statistically significant difference found between the BB and PB in regards to local control, disease-specific survival and overall survival. For the study cohort, FIGO stage and tumor grade were independent predictors of local control and disease-specific survival. As to be expected, there was a trend towards shorter overall survival for the PB patients (p=0.063). Conclusions: Athough tumor characteristics were more favorable in the baby boomers generation, local control and survival endpoints were not statistically different compared to pre boomers. As more baby boomers are diagnosed with endometrial carcinoma, further research is warranted to further elucidate the characteristic differences of endometrial carcinoma, if any, in this generation.

Clinicopathologic characteristics of endometrial cancer in Lynch syndrome.

5098 Background: Poor data exist on clinico-pathological description of endometrial cancer (EC) in Lynch syndrome (LS) compared with sporadic ones. To evaluate the clinico-pathological findings of Lynch-related EC to establish histological criteria to discriminate familial and sporadic EC and to decide the optimal management of patients. Methods: Retrospective study of prospective cohort of patients with LS in our institution from 1999 to 2011. We identified and described all cases of endometrial cancers. Management and follow-up were detailed. Results: Of a cohort of 126 patients with LS, 10 women developed endometrial carcinoma. The median age at diagnosis was 51 years (41-58). Five patients had an identified mutation (2 hMLH1, 2 hMSH2 and 1 hMSH6). In 9 cases, EC was the first Lynch-related tumor to occur. No patient developed ovarian cancer. All, except 2 patients (1 serous carcinoma and 1 clear cell carcinoma), had endometrioid adenocarcinoma (80%). Tumor grade was grade 1 in 3 patients, grade 2 in 5 and grade 3 in 2 patients. Forty per cent of patients had lymphovascular space involvement (LVSI). The FIGO stages were as follows: stage IA (n=7), stage IB (n=2) and stage IIIC (n=1). Four in ten patients had tumor located in the lower uterine segment. With a median follow-up of 14 months (range 9 – 40 months), recurrence occurred in one patient with a stage IB grade 2 endometrioid adenocarcinoma with LVSI. Conclusions: EC in LS is characterized by early age at onset, localization in lower uterine segment, and high rate of LVSI. Other data on histology and survival do not differ from sporadic cancers. These results suggest that we can consider conservative treatment in patients with good prognosis tumors. Further studies are required.

Interobserver Agreement for Endometrial Cancer Characteristics Evaluated on Biopsy Material

A shift toward a disease-based therapy designed according to patterns of failure and likelihood of nodal involvement predicted by pathologic determinants has recently led to considering a selective approach to lymphadenectomy for endometrial cancer. Therefore, it became critical to examine reproducibility of diagnosing the key determinants of risk, on preoperative endometrial tissue samples as well as the concordance between preoperative and postresection specimens. Six gynaecologic pathologists assessed 105 consecutive endometrial biopsies originally reported as positive for endometrial cancer for cell type (endometrioid versus nonendometrioid), tumor grade (FIGO 3-tiered and 2-tiered), nuclear grade, and risk category (low risk defined as endometrioid histology, grade 1 + 2 and nuclear grade <3). Interrater agreement levels were substantial for identification of nonendometrioid histology (κ = 0.63; SE = 0.025), high tumor grade (κ = 0.64; SE = 0.025), and risk category (κ = 0.66; SE = 0.025). The overall agreement was fair for nuclear grade (κ = 0.21; SE = 0.025). There is agreement amongst pathologists in identifying high-risk pathologic determinants on endometrial cancer biopsies, and these highly correlate with postresection specimens. This is ascertainment prerequisite adaptation of the paradigm shift in surgical staging of patients with endometrial cancer.

559 Hormonal pattern and metabolic features of endometrial cancer

559 Hormonal pattern and metabolic features of endometrial cancer