Endometrioid Endometrial Cancer Research Articles

Molecular classification and adjuvant treatment in endometrioid endometrial cancer with microcystic elongated and fragmented (MELF) invasion pattern.

To assess the characteristics, molecular classification, and role of adjuvant treatment in patients with endometrioid endometrial cancer (EEC) and microcystic elongated and fragmented (MELF) myometrial invasion pattern. This study included patients who were diagnosed with EEC with a MELF invasion pattern and underwent surgery from January 2019 to December 2023. We analyzed molecular classification, clinicopathological characteristics, and prognostic outcomes, including recurrence and adjuvant therapy. Out of 529 patients, 84 (15.9%) exhibited the MELF pattern, with 1 (1.2%) classified as POLE-mutation, 19 (22.6%) as mismatch repair deficient, 53 (63.1%) as no specific molecular profile, and 11 (13.1%) as p53-mutant subtype. Fifty (59.5%) patients with MELF invasion pattern received adjuvant chemotherapy (CT) ± external beam radiation therapy (EBRT), 19 (22.6%) received EBRT only, and 15 (17.9%) received no adjuvant treatment. Receiving adjuvant therapy was significantly associated with the risk level defined by the ESMO guideline for endometrial cancer (p = 0.002). With a median follow-up of 26 months (range: 1-59), the progression-free survival at 3-years for the MELF invasion patients was 91%. Seven patients with the MELF pattern experienced recurrence, of whom one was in stage IA (low risk, local recurrence) and did not receive any additional treatment, two were in stage IB (intermediate / high-intermediate risk, distant recurrence) and received EBRT only and the remaining four were in stage III to IV and had distant recurrence despite receiving adjuvant chemotherapy with or without EBRT. Among 43 intermediate- and high-intermediate-risk EEC patients, receiving CT ± EBRT was significantly associated with better DFS than without CT (p = 0.047). The presence of the MELF pattern in EEC should be incorporated into decision-making regarding adjuvant therapy. The use of adjuvant treatment should be tailored based on histology and molecular type.

Cervicovaginal lavages uncover growth factors as key biomarkers for early diagnosis and prognosis of endometrial cancer

Endometrial cancer (EC) rates are continuing to rise and it remains the most common gynecologic cancer in the US. Existing diagnostic methods are invasive and can cause pain and anxiety. Hence, there is a need for less invasive diagnostics for early EC detection. The study objective was to evaluate the utility of growth factors collected through minimally invasive cervicovaginal lavage (CVL) sampling as diagnostic and prognostic biomarkers for EC. CVL samples from 192 individuals undergoing hysterectomy for benign or malignant conditions were collected and used to quantify the concentrations of 19 growth and angiogenic factors using multiplex immunoassays. Patients were categorized based on disease groups: benign conditions (n = 108), endometrial hyperplasia (n = 18), and EC (n = 66). EC group was stratified into grade 1/2 endometrial endometrioid cancer (n = 53) and other EC subtypes (n = 13). Statistical associations were assessed using receiver operating characteristics, Spearman correlations and hierarchical clustering. Growth and angiogenic factors: angiopoietin-2, endoglin, fibroblast activation protein (FAP), melanoma inhibitory activity, and vascular endothelial growth factor-A (VEGF-A) were significantly (p < 0.0001) elevated in EC patients. A multivariate model combining 11 proteins with patient age and body mass index exhibited excellent discriminatory potential (area under curve = 0.918) for EC, with a specificity of 90.7% and a sensitivity of 87.8%. Moreover, angiopoietin-2, FAP and VEGF-A significantly (p < 0.05–0.001) associated with tumor grade, size, myometrial invasion, and mismatch repair status. Our results highlight the innovative use of growth and angiogenic factors collected through CVL sampling for the detecting endometrial cancer, showcasing not only their diagnostic potential but also their prognostic value.

Association between area deprivation index and outcomes of women with non-metastatic endometrioid endometrial cancer treated at a large urban academic hospital

Association between area deprivation index and outcomes of women with non-metastatic endometrioid endometrial cancer treated at a large urban academic hospital

Clinical activity of tazemetostat, an EZH2 inhibitor, among patients with advanced endometrioid endometrial cancer and ovarian clear cell carcinoma with and without ARID1A mutations (NRG-GY014)

Clinical activity of tazemetostat, an EZH2 inhibitor, among patients with advanced endometrioid endometrial cancer and ovarian clear cell carcinoma with and without ARID1A mutations (NRG-GY014)

Molecular subtypes of endometrioid endometrial cancer predict rates of lymph node and ovarian metastasis at the time of surgical staging

Molecular subtypes of endometrioid endometrial cancer predict rates of lymph node and ovarian metastasis at the time of surgical staging

Transvaginal ultrasound features of serous versus endometrioid endometrial cancer

Transvaginal ultrasound features of serous versus endometrioid endometrial cancer

Onvansertib exhibits anti-tumorigenic effects in pre-clinical models of endometrioid endometrial cancer

Onvansertib exhibits anti-tumorigenic effects in pre-clinical models of endometrioid endometrial cancer

Nab-Sirolimus plus letrozole in advanced or recurrent endometrioid endometrial cancer: A phase II, open-label, single-arm, prospective, multicenter study

nab-Sirolimus plus letrozole in advanced or recurrent endometrioid endometrial cancer: A phase II, open-label, single-arm, prospective, multicenter study

Analysis of Clinicopathological and Molecular Features of Microcystic, Elongated, and Fragmented Pattern Invasion in Endometrioid Endometrial Cancer.

Background: Microcystic, elongated, and fragmented (MELF) invasion is a special invasion pattern in endometrioid endometrial cancer (EEC). This study aimed to investigate the clinical, pathological, and molecular features of the MELF pattern and its prognostic value in patients with EEC. Materials and Methods: The clinical and pathological data of 342 patients with EEC were retrospectively collected at Peking University People's Hospital from January 2019 to December 2022. Some key clinicopathological features were evaluated, including the tumor grade, Federation of Gynecology and Obstetrics (FIGO) staging, cervical stromal involvement, lymph node status, and lymphatic vascular space infiltration (LVSI). Immunohistochemical staining and molecular tests were performed, and the relevant literature was reviewed. Results: The MELF pattern was more prevalent in low-grade EEC. A significant correlation was found between the MELF pattern and advanced FIGO staging, LVSI, the depth of myometrial invasion, cervical stromal involvement, and lymph node metastasis (LNM). The incidence of mismatch-repair-deficient (MMRd) proteins was much higher in the MELF group than in the no-MELF group. Molecular testing revealed that, after copy number-low (CNL), microsatellite instability-high (MSI-H) was the second-most frequent subtype in the MELF group. The recurrence risk did not significantly differ between the MELF and no-MELF groups, but the differences among the four molecular subtypes were statistically significant. However, the MELF group experienced a shorter recurrence time. Among the four molecular subtypes, the recurrence risk was the highest in the CNH subgroup, followed by the MSI-H subgroup. Conclusions: MELF is a special invasion pattern in EEC and is associated with distinct clinicopathological and molecular characteristics, including the latest 2023 FIGO staging. Further research is warranted to explore its implications for treatment strategies and patient outcomes.

Loss of vimentin expression in preoperative biopsies independently predicts poor prognosis, lymph node metastasis and recurrence in endometrial cancer

BackgroundPrecise preoperative risk classification of endometrial cancer is crucial for treatment decisions. Existing clinical markers often fail to accurately predict lymph node metastasis and recurrence risk. Loss of vimentin expression has emerged as a potential marker for predicting recurrence in low-risk endometrial cancer patients. We assessed whether vimentin expression in preoperative biopsies predicts poor prognosis and lymph node metastasis in a large multicentre cohort.MethodsVimentin expression was evaluated using immunohistochemistry in 1483 patients diagnosed with endometrial cancer across 14 hospitals in Europe. Expression levels of vimentin were analyzed in conjunction with clinical characteristics for predicting disease-specific survival and lymph node metastases.ResultsVimentin loss was significantly associated with aggressive disease and poor survival. Adjusted for clinicopathological variables, vimentin remained independently prognostic with a hazard ratio (HR) of 1.68 (95% CI 1.16–2.42, P = 0.006). Vimentin expression remained independently prognostic in endometrioid endometrial cancer- and FIGO staged 1 patient. Interestingly, vimentin loss independently predicted lymph node metastases, with an HR of 1.83 (95% CI 1.13–2.95, P = 0.014).ConclusionsLoss of vimentin in preoperative biopsies serves as an independent predictor of poor prognosis and lymph node metastases. Incorporating vimentin as a clinical marker can improve risk stratification and treatment decisions.

β‑catenin expression in endometrioid type endometrial cancer: Expression patterns and impact on disease outcomes.

Determination of nuclear and/or cytoplasmic expression of β-catenin by immunohistochemistry in patients with endometrial cancer (EC) may constitute a potential diagnostic method for identifying patients with a catenin β1 (CTNNB1) gene mutation and those at risk of disease recurrence. The present study aimed to investigate β-catenin expression patterns in hysterectomy specimens of patients with endometrioid type EC using immunohistochemistry, and to examine the prognostic impact of β-catenin. The study was a single-institutional, retrospective cohort trial enrolling consecutive patients with a postoperative histopathological diagnosis of endometrioid EC who underwent hysterectomy between January 2015 and December 2018. Histopathology slides from 75 patients were stained with a monoclonal antibody targeting the β-catenin protein. Any percentage of nuclear staining, whether focal or diffuse, was considered 'β-catenin nuclear-positive'. The cytoplasmic staining reaction of β-catenin was assessed based on the percentage of stained cells and staining intensity. Immune-reactivity score (IRS) values were determined by multiplying the scores for the percentage of staining and staining intensity. IRS values 0 to 2 were regarded as negative expression, 3 to 4 as low expression, 6 to 8 as moderate expression, and 9 to 12 as high expression. Recurrence-free survival (RFS) was used as the prognostic endpoint. Only 2 out of 75 tissue samples (2.7%) exhibited nuclear β-catenin expression, with a low staining percentage of 5%. By contrast, cytoplasmic staining was observed in all samples (100%). According to the IRS findings, 1.3% of the samples exhibited negative cytoplasmic expression, 42.7% low expression, 38.7% moderate expression and 17.3% high expression. Cox regression analysis revealed that staining with β-catenin, either nuclear or cytoplasmic, had no impact on RFS, and stage was the sole independent prognostic factor. In conclusion, based on these results, β-catenin expression in endometrioid EC was revealed to be mostly cytoplasmic, with only 2.7% of tissue samples exhibiting nuclear expression. Overall, β-catenin expression has no impact on RFS.

Racial discrepancies in initial presentation and diagnosis of patients with endometrial cancer.

89 Background: Endometrial cancer incidence and mortality are increasing, particularly in Black patients who have more aggressive non-endometrioid subtypes. Racial disparities in mortality may be partially contributable to early clinical factors including recognition of symptoms, type of evaluation, and referral timing. We evaluated differences in factors related to symptom appraisal and delays in diagnosis by race and histology. Methods: In this retrospective cohort study, we included patients diagnosed with endometrial cancer from 01/01/2019 to 09/01/2023 at a single institution who were enrolled in the Discovery and Evaluation of Testing for Endometrial Cancer in Tampons (DETECT) study. Demographic characteristics and factors regarding initial presentation and workup were obtained from the electronic medical record. We evaluated patient-reported length and type of symptoms at initial presentation, diagnostic imaging type, and time from initial presentation to time of imaging, tissue sampling, and referral to gynecologic oncology. We assessed differences by race and histology (endometrioid vs. non-endometroid) using chi-square and Kruskal-Wallis tests and analysis of variance. Results: Of the 335 patients included in our analysis, 237 (70.7%) had endometrioid and 98 (29.3%) had non-endometrioid histology. Patients with endometrioid histology were significantly more likely to be younger, White, non-smokers, and have higher obesity levels by body mass index than those with non-endometrioid histology (p=&lt;0.01). The length of symptoms at time of initial presentation was significantly longer in Black patients overall (p=0.01) and in Black patients with endometrioid histology compared to their White counterparts (p=0.04). A similar trend was seen in patients with non-endometrioid histology but was not statistically significant (p=0.15). There was no difference in type of symptoms reported. The type of imaging (p=0.005) differed significantly between endometrioid and non-endometrioid groups. White patients were more likely to have a transvaginal ultrasound performed at initial presentation (p=0.004). Black patients with endometrioid endometrial cancer were more likely to have a longer time period from initial presentation to referral to gynecologic oncology (p=0.04) despite having a shorter time between initial presentation and endometrial sampling (p=0.04). Conclusions: In our cohort, Black patients with endometrial cancer were more likely to have experienced symptoms for a longer time period prior to presentation, less likely to be evaluated with transvaginal ultrasound, and had a longer time period between initial presentation and referral to gynecologic oncology compared to White patients. Raising awareness and targeting these early steps in evaluation and detection of endometrial cancer may help decrease racial disparities in outcomes.

Performance of transvaginal ultrasound in evaluation of endometrioid versus non-endometrioid cancers.

401 Background: Measurement of endometrial thickness by transvaginal ultrasound (TVUS) is the standard of care for evaluation of patients with postmenopausal bleeding, the most common presenting symptom of endometrial cancer. However, the sensitivity of TVUS has not been clearly established in the setting of non-endometrioid histology, which is more aggressive and does not arise from endometrial hyperplasia. This study aims to evaluate the endometrial stripe (EMS) detection rate and sensitivity of TVUS in non-endometrioid compared to endometrioid endometrial cancers. Methods: In this retrospective cohort study, we included endometrial cancer cases diagnosed at a single institution from 01/01/2019 to 04/01/2024 who were enrolled in the Discovery and Evaluation of Testing for Endometrial Cancer in Tampons (DETECT) study who had TVUS during their initial clinical evaluation. Demographic characteristics and results from TVUS reports were obtained from the electronic medical record. Endometrial stripe thickness of less than 5mm is considered a negative result, whereas endometrial thickness of 5mm or greater (5mm+) is considered positive. The primary outcomes were the ability to measure EMS and the sensitivity of TVUS at a cutoff of 5mm+ for endometrial cancer detection, overall and by race and histology. We assessed differences using chi-squared tests. Results: Of the 349 patients included in our analysis, 247 (71%) had endometrioid histology, and 102 (21%) had non-endometrioid histology. There were 98 (28%) Black patients (49% non-endometrioid) and 242 (69%) White patients (22% non-endometrioid). The EMS was adequately measured in 98% of patients with endometrioid histology compared to 91% of patients with non-endometrioid histology (p=0.001). When stratified by race, EMS was visualized in 100% of Black patients with endometrioid histology but 89% of Black patients with non-endometrioid histology (p=0.02). This difference was seen but not significant in White patients with 98% measurable endometrial stripes in endometrioid cancer and 92% in non-endometrioid cancer (p=0.05). The ability to measure EMS was not different when compared by race alone. The sensitivity of TVUS (EMS of 5mm+) was higher in patients with endometrioid histology (99%) than patients with non-endometrioid histology (94%; p=0.03). Conclusions: In one of the largest and most diverse studies of TVUS performance in endometrial cancer patients to date, TVUS was more effective at visualizing the EMS and had higher sensitivity in patients with endometrioid compared to non-endometrioid endometrial cancers. While performance did not vary by race, the prevalence of non-endometrioid cancers was twice as high among Black compared to White patients. Our findings suggest that TVUS may be less accurate for diagnosing non-endometrioid endometrial cancer, which disproportionately affects Black women.

Oncologic outcomes based on lymphovascular space invasion in node-negative FIGO 2009 stage I endometrioid endometrial adenocarcinoma: a multicenter retrospective cohort study

BackgroundThe 2023 International Federation of Gynecology and Obstetrics (FIGO) staging system includes lymphovascular invasion quantification as a staging criterion for endometrioid endometrial carcinomas; no lymphovascular invasion and focal invasion (≤4...

The Intrauterine Device: How to Deploy This Strategy in the Molecular World?

Progestin-based therapy can safely be offered to a subset of patients with atypical endometrial hyperplasia or grade 1 endometrioid endometrial cancer who desire fertility preservation. A recent study shows that levonorgestrel intrauterine device confers durable clinical benefit and identifies possible immune mechanisms of relapse and resistance. See related article by Bowen et al., p. 5073.

Unravelling the molecular landscape of endometrial cancer subtypes: insights from multiomics analysis.

Endometrial cancer (EC) as one of the most common gynecologic malignancies is increasing in incidence during the past 10 years. Genome-Wide Association Studies (GWAS) extended to metabolic and protein phenotypes inspired us to employ multiomics methods to analyze the causal relationships of plasma metabolites and proteins with EC to advance our understanding of EC biology and pave the way for more targeted approaches to its diagnosis and treatment by comparing the molecular profiles of different EC subtypes. Two-sample mendelian randomization (MR) was performed to investigate the effects of plasma metabolites and proteins on risks of different subtypes of EC (endometrioid and nonendometrioid). Pathway analysis, transcriptomic analysis, and network analysis were further employed to illustrate gene-protein-metabolites interactions underlying the pathogenesis of distinct EC histological types. The authors identified 66 causal relationships between plasma metabolites and endometrioid EC, and 132 causal relationships between plasma proteins and endometrioid EC. Additionally, 40 causal relationships between plasma metabolites and nonendometrioid EC, and 125 causal relationships between plasma proteins and nonendometrioid EC were observed. Substantial differences were observed between endometrioid and nonendometrioid histological types of EC at both the metabolite and protein levels. The authors identified seven overlapping proteins (RGMA, NRXN2, EVA1C, SLC14A1, SLC6A14, SCUBE1, FGF8) in endometrioid subtype and six overlapping proteins (IL32, GRB7, L1CAM, CCL25, GGT2, PSG5) in nonendometrioid subtype and conducted network analysis of above proteins and metabolites to identify coregulated nodes. Our findings observed substantial differences between endometrioid and nonendometrioid EC at the metabolite and protein levels, providing novel insights into gene-protein-metabolites interactions that could influence future EC treatments.

How deep is too deep? Assessing myometrial invasion as a predictor of distant recurrence in stage I endometrioid endometrial cancer

ObjectivesThe goal of this study was to evaluate the depth of myometrial invasion as a predictor of distant recurrence in patients with node-negative stage IB endometrioid endometrial cancer.MethodsA retrospective multicenter...

Prognosis of isolated tumor cells and use of molecular classification in early stage endometrioid endometrial cancer

ObjectiveWe assessed the prognosis and molecular subtypes of early stage endometrioid endometrial cancer with isolated tumor cells within sentinel lymph nodes (SLNs) compared with node negative disease.MethodsPatients diagnosed with stage...

Exploring metastasis and recurrence patterns in low-risk grade 3 endometrial cancer: A multicenter retrospective cohort study

ObjectiveFemales with low-risk endometrial cancer typically have low lymph node metastasis risk and promising prognosis without lymphadenectomy. However, the impact of grade 3 endometrial cancer on nodal involvement, recurrence, and prognosis within this specific subgroup remains unclear. Therefore, in this study, we aimed to investigate the prognosis, patterns of metastasis, and recurrence in a subgroup of females with grade 3 early-stage low-risk endometrioid endometrial cancer. MethodsWe identified patients from the endometrial cancer cohorts of seven institutional hospitals. The study included patients who underwent hysterectomy between January 2013 and December 2021 with preoperative endometrioid histological type, less than half myometrial invasion, no tumor spread outside the corpus on imaging, normal CA-125 level, and histological grade 3. The clinicopathological characteristics and survival outcomes of the patients were collected. Recurrence-free survival was estimated using the Kaplan–Meier method and compared using the log rank test. ResultsOverall, 36 patients were included in this analysis. Of the 33 patients who underwent lymphadenectomy, 1 (1/33, 3.0 %) had lymph node metastasis and 27 (75.0 %) received adjuvant therapy. At a median follow-up of 58 months, three females (8 %) had recurrence and all cases involved lymph nodes. The 5-year recurrence-free survival was 88.7 %. No significant difference was observed in the recurrence-free survival between females who did and did not undergo lymphadenectomy (p = 0.554). ConclusionFemales diagnosed with low-risk grade 3 endometrial cancer typically have favorable prognosis. However, lymph node metastasis and recurrence risks still exist, with all recorded instances of recurrence involving lymph nodes.

The Effect of Prognostic Nutritional Index and Systemic Inflammatory Index in Endometrioid Type Endometrial Cancer

OBJECTIVES: The primary goal of the cohort was to show the relationship between systemic inflammatory index (SII) and prognostic nutritional index (PNI) values and the prognostic factors of endometrial cancer (EC), especially lymph node (LN) involvement, and lymphovascular space invasion (LVSI), which can not generally be evaluated preoperatively. STUDY DESIGN: This is a retrospective cohort based on reviews of patient records who were diagnosed with EC and underwent treatment between January 2014 and 2021. Complete blood counts and albumin level measurements were performed within 2 weeks before treatment. RESULTS: Two hundred twenty-seven patients with endometrioid type EC were included in the cohort. The mean follow-up was 35.4 ± 19.6 months. LVSI positivity was 8.2% in the presence of low SII and 44.1% in the presence of high SII (p&lt;0.001). LVSI positivity was 23.3% in the presence of low PNI and 11.1% in the presence of high PNI (p=0.025). Low and high PNI values do not affect disease-free (DFS) and overall survival (OS) significantly. 5-year mean DFS and OS differ significantly with low and high SII values. CONCLUSİON: SII and PNI values can be used to predict the presence of LVSI in the preoperative period, and to determine the extent of LN dissection and the surgical procedure Patients with high SII values had worse survival outcomes.