Early-stage Endometrioid Endometrial Carcinoma Research Articles

Clinicopathological Significance of Claudin-6 Immunoreactivity in Low-grade, Early-stage Endometrioid Endometrial Carcinoma.

Dysregulation of claudin 6 (CLDN6) expression has been widely documented in various malignancies. CLDN6 is aberrantly expressed in many types of human carcinomas; however, its clinical significance in endometrial carcinoma has seldom been investigated. This study aimed to examine the immunohistochemical expression status of CLDN6 in low-grade, early-stage endometrioid endometrial carcinoma (LGES-EEC) and to assess its clinicopathological significance. We performed immunostaining for CLDN6 in 118 tissue samples from LGES-EECs. Protein expression levels were interpreted using a semi-quantitative histoscore method. All statistical analyses were performed. CLDN6 was primarily localized along the membranes of the tumor cells. We considered histoscore ≥10 (the staining proportion ≥5% and intensity ≥2) as positive immunoreactivity for CLDN6. Twenty-six of the 118 patients (22.0%) showed CLDN6 positivity. Positive CLDN6 expression was significantly associated with deeper myometrial invasion (p=0.001), higher initial stage (p=0.015), and substantial lymphovascular space invasion (p=0.018). Aberrant CLDN6 expression is involved in tumor progression in LGES-EECs. In addition, targeting CLDN6 may offer clinical utility in patients with endometrial carcinoma.

Non-operative management of clinical early-stage endometrioid endometrial carcinoma: Hormonal or radiation therapy? (1290)

Non-operative management of clinical early-stage endometrioid endometrial carcinoma: Hormonal or radiation therapy? (1290)

CTNNB1 p.D32A (c.95A > C) somatic mutation in stage I grade 1 endometrioid endometrial carcinoma with lung metastasis: a case report

BackgroundMost endometrial cancers are of low histological grade and uterine-confined, with a high 5-year survival rate. However, a small subset of women with low-grade and early-stage endometrioid endometrial cancer experience recurrence and death; thus, a more precise risk-stratification is needed.Case presentationA 29-year-old woman presented with abnormal vaginal bleeding and was diagnosed with FIGO grade 1 endometrioid endometrial carcinoma by curettage. Comprehensive cancer staging including pelvic and para-aortic lymphadenectomy was then performed. Postoperative pathological findings suggested an FIGO grade 1 endometrioid endometrial carcinoma infiltrating the superficial muscle layer. The patient did not receive adjuvant therapy. After 4 years of follow-up, the patient returned to our institution with lung metastasis. She underwent thoracoscopic resection of the affected lobes, followed by six cycles of combined chemotherapy of paclitaxel and carboplatin. Next-generation sequencing showed that the primary and lung metastatic tumors shared 4 mutations: PTEN (p.P248Lfs*8), CTNNB1 (p.D32A), BCOR (p.N1425S) and CBL (p.S439N). Immunohistochemistry revealed nuclear location of β–catenin in the primary and lung metastatic tumor samples, indicating abnormal activation of β–catenin.ConclusionCTNNB1p.D32A (c.95A > C) mutation may be related to lung metastasis in this patient with low-grade early-stage endometrioid endometrial carcinoma.

Prospective analysis of the impact of adjuvant treatment with external beam radiation therapy and vaginal brachytherapy on health-related quality of life in patients with early-stage endometrioid endometrial carcinoma.

Our study evaluates the impact of adjuvant treatment with external beam radiotherapy (EBRT) combined with vaginal high dose rate brachytherapy (HDR BT) on health related quality of life (HRQL) in patients with early stage endometrioid endometrial carcinoma. From March 2019 to February 2021, 60 patients were enrolled with early stage endometrioid endometrial carcinoma, and qualified to adjuvant treatment after hysterectomy. HRQL was assessed using the EORTC QLQ-C30 questionnaire, with the endometrial cancer-specific HRQL module EORTC QLQ-EN24. Questionnaires were completed in four timepoints during adjuvant radiotherapy. A significant decrease in mean global health status / quality of life (p < 0.001) and role functioning (p = 0.028) was noted, as assessed in EORTC QLQ-C30 scale. Among the EORTC QLQ-C30 symptoms scales, significant differences were noted in the fatigue scale (p = 0.003), pain scale (p = 0.001), constipation scale (p < 0.001) and diarrhea scale (p < 0.001) over time. The EORTC QRQ-EN24 analysis showed significant deterioration in the urological symptoms scale (p < 0.001), gastrointestinal symptoms scale (p < 0.001) and in the mean pain in back and pelvis scale (p = 0.003). Adjuvant radiotherapy in patients with early-stage endometrioid endometrial cancer after hysterectomy is associated with worse quality of life, especially due to the toxicity of the treatment in relation to the gastrointestinal tract and urinary system.

The impact of adjuvant treatment with external beam radiotherapy and vaginal brachytherapy on health-related quality of life in patients with early-stage endometrioid endometrial carcinoma - initial results of a prospective study.

Our study evaluates the impact of adjuvant treatment with external beam radiotherapy (EBRT) combined with vaginal high-dose-rate brachytherapy (HDR BT) on health-related quality of life (HRQL) in patients with early-stage endometrioid endometrial carcinoma. We assessed HRQL of patients based on the EORTC QLQ-C30 questionnaire, with endometrial cancer specific HRQL module - EORTC QLQ-EN24. From March 2019 to April 2020 we enrolled 20 patients with early-stage endometrioid endometrial carcinoma, qualified for adjuvant treatment after hysterectomy. We compared the scores measured with the questionnaires at the beginning and at the end of the treatment. There was a statistically significant decrease in the mean of global health status/quality of life assessed according to the EORTC QLQ-C30 scale, from 62.25 ± 13.12 at the beginning of the adjuvant radiotherapy to 55.85 ± 14.68 at the end of the treatment (p = 0.047). The mean appetite loss score was higher at the onset of the treatment as compared to its value after EBRT, 19.9 ± 27.33 vs 11.6 ± 19.52 (p = 0.043). Similarly to the mean constipation score, which was 29.85 ± 30.40 vs 11.6 ± 19.52 (p = 0.013). The mean diarrhoea symptom scale increased from 16.55 ± 20.16 to 56.75 ± 36.10 (p = 0.001). In the EORTC QLQ-EN24 scales, gastrointestinal symptoms scores were higher at the end of the treatment, (with the mean of 26.45 ± 22.76) as compared to 14.30 ± 16.52 at the beginning of EBRT (p = 0.003). Patients who receive adjuvant radiotherapy have decreased quality of life during the treatment reporting more serious gastrointestinal symptoms. The potential risk of treatment-related toxicity should be taken into account during the treatment planning process in order to minimize the deterioration of HRQL.

Impact of surgical approach on prevalence of positive peritoneal cytology and lymph-vascular invasion in patients with early-stage endometrial carcinoma: a National Cancer Database study

ObjectiveTo investigate the prevalence of positive peritoneal cytology and lymph-vascular invasion by surgical approach among patients with early stage endometrioid endometrial carcinoma undergoing hysterectomy.MethodsThe National Cancer Database was accessed and...

Assessment of lymphovascular invasion in early stage endometrial carcinoma -a retrospective study

IntroductionEndometrial carcinoma is associated with several known prognostic factors. Recently, lymphovascular invasion (LVI) has gained a prominent position in the risk assessment of early endometrioid endometrial carcinoma, in identifying patients who can benefit from adjuvant radiation therapy. This study aims to assess LVI in early-stage endometrioid endometrial carcinoma accurately with emphasis on its extent /grading. We also propose a few local recommendations for improving LVI reproducibility in endometrial carcinoma to guide future studies.MethodsThe duration of this retrospective study was 2 years. Early-stage I (Ia and Ib), and grade 1 and 2 endometrioid endometrial carcinomas were included. 03 reviewers independently recorded their findings on H&E stained slides. LVI was graded as none, focal and substantial. In discordant cases, immunohistochemical stain CD 31 was used.All the data was entered in the statistical software SPSS version 26 and analyzed for frequencies. The relationships between various histological parameters assessed and the degree of reproducibility for LVI amongst various observers were also determined.ResultsOut of a total of 70 cases of endometrioid carcinoma diagnosed on hysterectomy specimen, only 32 met our inclusion criteria. The rate of LVI positivity was 6.3 %, 34.4 %, and 37.5 % respectively for reviewers 1, 2, and 3. The degree of reproducibility in LVI assessment and LVI grading was significant amongst reviewers 2 and 3. Also, a significant association was drawn between tumor grade and LVI.ConclusionDespite limitations in our study we recommend including both LVI assessment and grading in routine reporting formats locally. By adding a second reviewer in LVI assessment and using CD31 in discrepant cases LVI positivity can be significantly increased.

Fibroblast Growth Factor Receptor 2 Isoforms Detected via Novel RNA ISH as Predictive Biomarkers for Progestin Therapy in Atypical Hyperplasia and Low-Grade Endometrial Cancer

Simple SummaryWomen diagnosed with low-grade endometrioid cancer (EEC) and its precursor lesion, atypical hyperplasia (AH) are frequently treated with hormonal therapy including levonorgestrel releasing intrauterine device (LNG-IUD) as an alternative to surgery. Biomarkers that inform which group of patients are more likely to respond to LNG-IUD are not available. The aim of this study was to document the response rate to LNG-IUD therapy in women with AH and EEC and identify potential biomarkers to guide treatment response. The overall response rate (ORR) for the whole cohort was 30/69 (~44%) with a higher ORR seen in AH (64%) compared to EEC (23%). Fibroblast Growth Factor Receptor (FGFR2) isoforms were detected using RNA in situ hybridization. The FGFR2c isoform was expressed in 16.7% of the samples, with those expressing FGFR2c 5-times more likely to have treatment failure. FGFR2 isoform expression could be used to guide treatment decisions following confirmation of this finding in an independent study.Women with atypical hyperplasia (AH) or well-differentiated early-stage endometrioid endometrial carcinoma (EEC) who wish to retain fertility and/or with comorbidities precluding surgery, are treated with progestin. Clinically approved predictive biomarkers for progestin therapy remain an unmet need. The objectives of this study were to document the overall response rate (ORR) of levonorgestrel intrauterine device (LNG-IUD) treatment, and determine the association of FGFR2b and FGFR2c expression with treatment outcome. BaseScope RNA ISH assay was utilized to detect expression of FGFR2b and FGFR2c mRNA in the diagnostic biopsies of 89 women (40 AH and 49 EEC) treated with LNG-IUD. Detailed clinical follow-up was available for 69 women which revealed an overall response rate (ORR) of 44% (30/69) with a higher ORR seen in AH (64%) compared to EEC (23%). The recurrence rate in women who initially responded to LNG-IUD was 10/30 (33.3%). RNA ISH was successful in 72 patients and showed FGFR2c expression in 12/72 (16.7%) samples. In the 59 women with detailed clinical follow-up and RNA-ISH data, women with tumours expressing FGFR2c were 5-times more likely to have treatment failure in both univariable (HR 5.08, p < 0.0001) and multivariable (HR 4.5, p < 0.002) Cox regression analyses. In conclusion, FGFR2c expression appears to be strongly associated with progestin treatment failure, albeit the ORR is lower in this cohort than previously reported. Future work to validate these findings in an independent multi-institutional cohort is needed.

Integrating pathology, chromosomal instability and mutations for risk stratification in early-stage endometrioid endometrial carcinoma

BackgroundRisk stratifications for endometrial carcinoma (EC) depend on histopathology and molecular pathology. Histopathological risk stratification lacks reproducibility, neglects heterogeneity and contributes little to surgical procedures. Existing molecular stratification is useless in patients with specific pathological or molecular characteristics and cannot guide postoperative adjuvant radiotherapies. Chromosomal instability (CIN), the numerical and structural alterations of chromosomes resulting from ongoing errors of chromosome segregation, is an intrinsic biological mechanism for the evolution of different prognostic factors of histopathology and molecular pathology and may be applicable to the risk stratification of EC.ResultsBy analyzing CIN25 and CIN70, two reliable gene expression signatures for CIN, we found that EC with unfavorable prognostic factors of histopathology or molecular pathology had serious CIN. However, the POLE mutant, as a favorable prognostic factor, had elevated CIN signatures, and the CTNNB1 mutant, as an unfavorable prognostic factor, had decreased CIN signatures. Only if these two mutations were excluded were CIN signatures strongly prognostic for outcomes in different adjuvant radiotherapy subgroups. Integrating pathology, CIN signatures and POLE/CTNNB1 mutation stratified stageIendometrioid EC into four groups with improved risk prognostication and treatment recommendations.ConclusionsWe revealed the possibility of integrating histopathology and molecular pathology by CIN for risk stratification in early-stage EC. Our integrated risk model deserves further improvement and validation.

Myoinvasive Pattern as a Prognostic Marker in Low-Grade, Early-Stage Endometrioid Endometrial Carcinoma.

Low-grade and early Federation for Gynecology and Obstetrics (FIGO) stage endometrioid endometrial carcinomas (EEC) have an excellent prognosis. However, approximately 10% of patients develop recurrence, which cannot be correctly predicted at diagnosis. We evaluated myoinvasive patterns as a prognostic factor of relapse in low-grade, early-stage EEC. Two-hundred and fifty-eight cases were selected according to the following inclusion criteria: (i) endometrioid endometrial carcinomas, (ii) grade 1 or 2 with (iii) FIGO stage I or II, and (iv) clinical follow-up. Slides were reviewed to annotate the myoinvasive pattern present in each case (infiltrative glands, microcystic, elongated and fragmented –MELF-, broad front, adenomyosis-like and adenoma malignum). Microsatellite instability was studied by immunoexpression of mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6). There were 29 recurrences (11.2%) among the 258 cases analysed. A predominant broad front myoinvasive pattern was significantly associated with tumour relapse (p = 0.003). The presence of a pattern of infiltrative glands (p = 0.001) and microsatellite instability (p = 0.004) were associated with lower disease-free survival, without having an impact on overall survival. Our observations suggest the potential value of the pattern of myoinvasion as a prognostic factor in low-grade, early-stage endometrioid endometrial carcinoma.

Does Charlson Comorbidity Score Dilute the Survival Impact of Adjuvant Radiation Therapy in Women with Early Stage Endometrial Cancer? A Matched Analysis

To determine the impact of Age-Adjusted Charlson Comorbidity index (AACCI) score on survival outcomes in women with early stage endometrial cancer using a matched analysis methodology. After institutional review board-approval, 388 women with FIGO stage I-II uterine endometrioid carcinoma were included in this study. 194 women who had received adjuvant radiation treatment (RT) were exactly matched with 194 women who were observed after hysterectomy (1:1 match, strictly based on FIGO stage and grade). AACCI score at time of hysterectomy was determined by trained physicians based on review of all available medical records. Based on AACCI, the study cohort was divided into those with AACCI score of 0 (healthier) vs. those with a score of ≥1. Univariate and multivariate modeling with Cox regression analysis was used to determine significant predictors of recurrence-free (RFS), disease-specific (DSS) and overall survival (OS). Median follow-up for the study cohort was 58 months. While women who received adjuvant RT had a significantly higher 5-year RFS (90% vs. 78%, p=0.002), there was no significant difference in 5-year OS (88% vs. 86%, p=0.589). When accounting for comorbidity burden in women who received RT, 5-year OS was (94% vs. 81%, p=0.017) for women with AACCI score of 0 compared to those with a score of > 1, with an absolute difference of 13% at 5-year and 23% at 10 year OS. Similarly, for those who were observed after hysterectomy, 5-year OS was 91% vs 80%, p=0.011. The impact of AACCI was not statistically significant on 5-year RFS and DSS. On multivariate analyses for the entire cohort, higher AACCI score, older age, tumor grade (3 vs 1), and lymphovascular space invasion (LVSI) were significantly independent predictors for shorter OS. LVSI and grade 3 were the only two independent predictors of DSS. The lack of adjuvant RT and the presence of LVSI were significant predictors of worse RFS. Comorbidity burden is just as important as traditional prognostic variables for predicting overall survival in women with early-stage endometrioid endometrial carcinoma. Its prognostic impact should be accounted for in future prospective studies of women with endometrial cancer. On the other hand, its prognostic impact was not observed for RFS and DSS.

Use of next-generation sequencing (NGS) panels to predict recurrence in low-grade, early-stage endometrioid endometrial carcinoma.

5580Background: Predicting recurrence in low grade, early stage endometrial cancer (EC) is both difficult and important, as recurrence outside the pelvis is typically incurable. We sought to determ...

Integrative Protein-Based Prognostic Model for Early-Stage Endometrioid Endometrial Cancer.

Endometrioid endometrial carcinoma (EEC) is the major histologic type of endometrial cancer, the most prevalent gynecologic malignancy in the United States. EEC recurrence or metastasis is associated with a poor prognosis. Early-stage EEC is generally curable, but a subset has high risk of recurrence or metastasis. Prognosis estimation for early-stage EEC mainly relies on clinicopathologic characteristics, but is unreliable. We aimed to identify patients with high-risk early-stage EEC who are most likely to benefit from more extensive surgery and adjuvant therapy by building a prognostic model that integrates clinical variables and protein markers. We used two large, independent early-stage EEC datasets as training (n = 183) and validation cohorts (n = 333), and generated the levels of 186 proteins and phosphoproteins using reverse-phase protein arrays. By applying an initial filtering and the elastic net to the training samples, we developed a prognostic model for overall survival containing two clinical variables and 18 protein markers and optimized the risk group classification. The Kaplan-Meier survival analyses in the validation cohort confirmed an improved discriminating power of our prognostic model for patients with early-stage EEC over key clinical variables (log-rank test, P = 0.565 for disease stage, 0.567 for tumor grade, and 1.3 × 10(-4) for the integrative model). Compared with clinical variables (stage, grade, and patient age), only the risk groups defined by the integrative model were consistently significant in both univariate and multivariate analyses across both cohorts. Our prognostic model is potentially of high clinical value for stratifying patients with early-stage EEC and improving their treatment strategies.

Abstract 5301: Integrative protein-marker prognostic model for early-stage endometrioid endometrial carcinoma

Abstract Endometrioid endometrial carcinoma (EEC) is the major histological type of endometrial cancer, the most prevalent gynecologic malignancy in USA. EEC recurrence or metastasis is associated with an abysmal prognosis. Early-stage EEC is generally curable, but a subset has high risk of recurrence or metastasis. Prognosis estimation for early-stage EEC mainly relies on clinicopathological characteristics, but is unreliable. We aimed to identify patients with high-risk early-stage EEC who are most likely to benefit from more extensive surgery and adjuvant therapy by building a prognostic model that integrates clinical variables and protein markers. We employed two large, independent EEC datasets as training and validation cohorts, and generated the levels of 186 proteins and phosphoproteins using reverse-phase protein arrays. Using the training samples, we developed a predictive model containing two clinical factors and 18 protein markers and optimized the risk group classification. Kaplan-Meier survival analyses in the validation cohort confirmed an improved prognostic power. Compared with clinical variables (stage, grade, and patient age), only the risk groups defined by the integrative model were consistently significant in both univariate and multivariate analyses across both cohorts. Our prognostic model is potentially of high clinical value for stratifying patients with early-stage EEC and optimizing their treatment strategies. Note: This abstract was not presented at the meeting. Citation Format: Han Liang, UT MD Anderson RPPA/TCGA working group. Integrative protein-marker prognostic model for early-stage endometrioid endometrial carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5301. doi:10.1158/1538-7445.AM2015-5301

Survival Rate of Early Stage Endometrioid Adenocarcinoma of Endometrium Treated at Srinagarind Hospital

To evaluate the survival outcome of early stage endometrioid adenocarcinoma of the endometrium with risk factors for locoregional recurrence treated with combined pelvic external beam radiotherapy (EBRT) and vaginal brachytherapy (VBT) after comprehensive surgery. Post-operative radiotherapy by pelvic EBRT and VBT for early stage endometrioid endometrial carcinoma resulted in excellent pelvic control with acceptable complications. This study showed no significant relationships between age, stage, histologic grade and LVSI and overall survival rate. The 5-year overall survival rate (OS) of early stage endometrioid type of endometrial carcinoma was 85.7%. Acute toxicity occurred in 38.1% of the patients, all of whom were grade 1 or 2. Total late toxicity developed in 42.9% of study group, in which 36.99% of them were grade 1-2 and 4.76% were grade 3-4. Post-operative radiotherapy by pelvic EBRT and VBT is acceptable for early stage endometrioid endometrial carcinoma, independent of age, stage, histologic grade and LVSI.

Impact of Age-Adjusted Charlson Comorbidity score on outcomes for patients with early-stage endometrial cancer

ObjectivesTo determine the impact of Age-Adjusted Charlson Comorbidity (AAC) index score on survival outcomes for patients with early stage endometrial cancer. MethodsAfter IRB-approval, AAC score at time of hysterectomy was retrospectively tabulated by physician chart review for 671 patients with 2009 FIGO stage I–II endometrioid adenocarcinoma. Patients were grouped based on their AAC scores as follows: 0–1 (n=204), 2–3 (n=293) and >3 (n=174). Kaplan–Meier and log-rank test methods and univariate and multivariate modeling with Cox regression analysis was used to determine significant predictors of each survival endpoint. ResultsAfter a median follow-up of 85months, 225 deaths were recorded (34 from EC and 191 from other causes) with a 7-year Overall (OS) and Disease-specific survival (DSS) of 77.6% and 94.0%, respectively. Based on AAC grouping, the 7-year OS, DSS, and Recurrence-free survival (RFS) were: 92.9%, 96.8%, and 94.9% for AAC 0–1; 81.7%, 95.3%, and 89.8% for AAC 2–3: and 56%, 88.2%, and 84.9% for AAC>3 (p<0.0001, p=0.005 and p=0.013, respectively). On multivariate analyses, higher AAC score, tumor grade, lower uterine segment involvement, and lymphovascular space invasion were significantly independent predictors for shorter OS, while for DSS and RFS, higher tumor grade and lymphovascular space invasion were significant predictors of worse outcome, but higher AAC score was not. ConclusionsComorbidity score is as important as pathological features for predicting overall survival outcomes in patients with early-stage endometrioid endometrial carcinoma. Higher AAC scores accurately predicted for worse OS. Comorbidity score should be considered in prospective clinical trials of endometrial carcinoma.

Epithelial to mesenchymal transition in early stage endometrioid endometrial carcinoma

Epithelial to mesenchymal transition is thought to be implicated in tumor invasion and metastasis. To investigate its role in myometrial invasion, samples from 42 stage I (confined to the corpus) endometrioid endometrial carcinomas were analyzed. All E-cadherin repressors (SNAI1, SNAI2 (SLUG), ZEB1, HMGA2, and TWIST1) had a higher expression in endometrioid endometrial carcinomas than in normal endometrium (P < .0001), whereas CDH1 (E-cadherin gene) tended to be lower. In comparison with nonmyoinvasive (stage IA) tumors, those with deep myometrial invasion (stage IC) had increased messenger RNA expression of SLUG, ZEB1, and HMGA2 (P < .001). Furthermore, samples from the myoinvasive front of deeply invasive tumors had higher levels of SLUG, ZEB1, and HMGA2 than the corresponding superficial samples. Immunohistochemical analysis of these cases revealed that the decrease in E-cadherin was concordant with an increase in Snail and Twist protein expression. Trying to induce epithelial to mesenchymal transition in endometrioid endometrial carcinomas, we initially produced persistent activation of this pathway in Ishikawa cells. The cell line was infected with lentiviruses carrying the V600E mutation of BRAF, inducing loss of β-catenin, E-cadherin, and cytokeratin and increase in vimentin and Snail. These changes were mediated by ERK1/2 phosphorylation, which was also increased at the myoinvasive front. Furthermore, MEK1/2 inhibitor UO126 reversed the mesenchymal phenotype. Our findings suggest that epithelial to mesenchymal transition regulators are implicated in myometrial invasion of endometrioid endometrial carcinoma and may be potential therapeutic targets through the MAPK/ERK pathway.

Lower Uterine Segment Involvement is Associated with Poor Outcomes in Early-Stage Endometrioid Endometrial Carcinoma

The clinicopathologic significance of lower uterine segment involvement (LUSI) in endometrial cancer patients remains unclear. Although LUSI has been reported to be a prognostic indicator, literature is limited. We studied 481 surgically staged endometrioid endometrial cancers with disease confined to the uterus (FIGO 1988 stage I or II). Primary outcomes were overall survival (OS) and disease-free survival (DFS). The relationships between LUSI and OS and DFS were assessed using the Kaplan-Meier method and Cox proportional hazard models. The t test or Fisher exact test was used for evaluating relationships between variables of interest. LUSI was present in 223 cases (46.4%), and was associated with both decreased disease free survival (P = 0.02) and overall survival (P = 0.01) in univariate analysis. Multivariate analysis confirmed the association between LUSI and increased risk for recurrence [hazard ratio (HR) 2.27; 95% confidence interval (95% CI) 1.09-4.7; P = 0.03] and increased mortality (HR 1.76; 95% CI 1.12-2.78; P = 0.01). LUSI in patients with early-stage endometrioid endometrial cancer is associated with decreased survival.