Evaluation of systemic and local immune responses in patients with endometrial cancer.

5594 Background: Several studies suggest that systemic immune response (SIR) and local immune response (LIR) have independent roles in multiple types of cancer. In endometrial cancer (EC), the correlation between SIR and LIR and its prognostic value remains unclear. Methods: A total of 146 EC patients (stage I-IV) who had undergone surgery from 2009 to 2015, were identified from a prospective institutional database. Lymphocyte/monocyte ratio (LMR) to represent SIR was calculated from preoperative blood samples. The presence of intratumoral and peritumoral infiltrating lymphocytes (TILs) on hematoxylin and eosin-stained slides was considered as a surrogate of LIR. LMR and TILs were correlated to pathological findings and survival outcomes (overall survival: OS, disease free survival: DFS). Results: A LMR cutoff value of 4.4 for survival was determined based on receiver operating characteristic (ROC) curve analysis. LMR high was significantly associated with endometrioid histology (p=0.03), lower grade (G1-2; p=0.003), < 50% myometrial invasion (p=0.01) and I-II stage (p=0.02). TILs were correlated with MSI-high (p<0.005), but not with LMR (p=0.3). Low LMR was associated with worse 5-year OS rates (64.5% vs 93.9%; p<0.01) and presence of TILs with better 5-years OS rates (72% vs 27%; p=0.04). On multivariate analysis (table 1) LMR, histology, stage and grade remained independent prognostic factors for OS (p=0.01). Using the combination of LMR and TILs, four groups with decreasing 5-years OS rates were identified: LMR-high/TILs+ (100%) > LMR-high/no-TILs (87%) > LMR-low/TILs+ (71%) > LMR-low/no-TILs (61%). Conclusions: In our series of resected EC patients, SIR (defined by LMR) constituted an independent prognostic factor for OS and LIR for DFS. We did not find any correlation between SIR and LIR, but the combination of both higher SIR and LIR showed better OS. [Table: see text]

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Impact of Hormone Receptor Status and Ki-67 Expression on Disease-Free Survival in Patients Affected by High-risk Endometrial Cancer

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000001191 ◽

2018 ◽

Vol 28 (3) ◽

pp. 505-513 ◽

Cited By ~ 7

Author(s):

Violante Di Donato ◽

Valentina Iacobelli ◽

Michele Carlo Schiavi ◽

Vanessa Colagiovanni ◽

Irene Pecorella ◽

...

Keyword(s):

Endometrial Cancer ◽

High Risk ◽

Disease Free Survival ◽

Myometrial Invasion ◽

Depth Of Invasion ◽

Prognostic Impact ◽

Ki 67 ◽

Free Survival ◽

Gynecology And Obstetrics ◽

Disease Free

ObjectivesThe aim of this study was to evaluate the immunohistochemical (IHC) expression of Ki-67, estrogen receptors α (ERsα), and progesterone receptors (PRs) in high-risk endometrial cancer patients and to assess their prognostic impact.Methods/MaterialsImmunohistochemical expression of Ki-67, ERsα, and PRs was evaluated in primary untreated endometrial cancer. The correlation among IHC staining and risk factors of recurrence such as age, Federation International of Gynecology and Obstetrics stage, grading, depth of invasion, and metastatic spread was assessed.ResultsEighty-two patients were available for the analysis. Mean ± SD age was 65.05 ± 10.48 years. The IHC assessment revealed a lack of ERα in 46.3% and of PR in 48.7% as well as a high Ki-67 in 31.7%. Loss of ERα and PR was associated with a significant higher rate of advanced stage of disease, a higher frequency of G3 tumors, and a myometrial invasion greater than 50%. A strong Ki-67 expression correlated with a deeper myometrial invasion. Analysis of the interrelationship between receptor immunonegativity revealed a relevant association of ERα immunolocalization with PR and with a high Ki-67 expression. The present study also showed that loss of ERα (P = 0.003), advanced Federation International of Gynecology and Obstetrics stage (P < 0.001), and high Ki-67 (P = 0.004) were independent prognostic factors of a shorter disease-free survival. Importantly, loss of ERα, loss of PR, and a high Ki-67 were correlated with a higher incidence of distant recurrence.ConclusionsA systematic immunohistochemistry should be a key step in the therapeutic algorithm and could contribute to the identification of high-risk tumors.

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Clinicopathological Role of Serum-Derived Hyaluronan-Associated Protein (SHAP)-Hyaluronan Complex in Endometrial Cancer

Obstetrics and Gynecology International ◽

10.1155/2011/739150 ◽

2011 ◽

Vol 2011 ◽

pp. 1-10 ◽

Cited By ~ 4

Author(s):

Hiromitsu Yabushita ◽

Keita Iwasaki ◽

Kouhei Kanyama ◽

Yukihiko Obayashi ◽

Lisheng Zhuo ◽

...

Keyword(s):

Endometrial Cancer ◽

Cancer Patients ◽

Histological Grade ◽

Disease Free Survival ◽

Myometrial Invasion ◽

Serum Levels ◽

Free Survival ◽

Vascular Space ◽

Disease Free

The role of hyaluronan (HA), serum-derived HA-associated protein (SHAP)-HA complex and hyaluronan synthase (HAS) in endometrial carcinomas was investigated. The relationship of metalloproteinase (MMP) and its inhibitor (TIMP) with HA and the SHAP-HA complex was also examined. The expression of HAS1 was related to the depth of myometrial invasion and lymph-vascular space involvement. The serum levels of HA, SHAP-HA complex, MMP-9, and TIMP-1 were increased in related with the depth of myometrial invasion, histological grade and lymph-vascular space involvement. They were also higher in the HAS1-positive group compared to -negative group. The serum concentrations of HA and SHAP-HA complex had a significant correlation with the MMP-9 and TIMP-1. The patients with elevated SHAP-HA complex had the shorter disease-free survival. The multivariate analysis revealed that the SHAP-HA complex was the independent variable for disease-free survival of endometrial cancer patients. In conclusion, the elevation of serum SHAP-HA complex depended on the HAS1 expression and the SHAP-HA complex is a useful marker to predict disease recurrence in endometrial cancer patients. The SHAP-HA complex may promote the lymph-vascular space involvement and the synthesis and activation of MMP-9 and TIMP-1 in the progression of endometrial cancer.

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Disease Free Survival of Stage I Endometrial Cancer after Surgery with or without Adjuvant Treatment

Folia Medica Indonesiana ◽

10.20473/fmi.v55i1.24373 ◽

2021 ◽

Vol 55 (1) ◽

pp. 37

Author(s):

Woraluk Moradokkasem ◽

Nungrutai Saeaib ◽

Tippawan Liabsuetrakul

Keyword(s):

Endometrial Cancer ◽

Adjuvant Treatment ◽

Disease Free Survival ◽

Myometrial Invasion ◽

Stage I ◽

Rank Test ◽

Free Survival ◽

Factors Associated ◽

Disease Free ◽

Better Than

This study aimed to define the disease free survival (DFS) and factors associated with recurrence in stage I endometrial cancer after surgery with and without adjuvant treatment. The demographic data, pathological results, adjuvant treatment (AT) and the outcome of patients with endometrial cancer stage I after surgery in Songklanagarind Hospital between January 2002 and July 2014 were collected. The DFS was analyzed by survival analysis and represented by Kaplan–Meier curves. The difference of DFS between AT and non-adjuvant treatment (NAT) groups was tested by the log-rank test. Distributions of risk factors by AT and recurrent status were analyzed using chi-square or Fisher exact tests for discrete factors, and unpaired t or Wilcoxon rank-sum tests for continuous factors. The 5-year DFS was; 91.6%, from a total of 268 patients. DFS in the NAT group was significantly better than that in the AT group (95.2 versus 86.5%, p-value = 0.01). Factors associated with recurrence in the NAT group were age, tumor grading, tumor size, and presence of lymphovascular involvement. Among the AT group, age and ratio of myometrial invasion were associated with recurrence. DFS in NAT was better than in AT and the potential factors associated with recurrence, after surgery with or without AT, were not the same.

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Understanding the role of indoleamine-2,3-dioxygenase and stromal differentiation in rare subtype endometrial cancer

Rare Tumors ◽

10.1177/20363613211044690 ◽

2021 ◽

Vol 13 ◽

pp. 203636132110446

Author(s):

Dongling Wu ◽

Sean Hacking ◽

Jin Cao ◽

Mansoor Nasim

Keyword(s):

Endometrial Cancer ◽

Endometrial Carcinoma ◽

Immune Cell ◽

Disease Free Survival ◽

Myometrial Invasion ◽

Tumor Stage ◽

Free Survival ◽

Indoleamine 2,3 Dioxygenase ◽

Disease Free

Endometrial cancer (EC) is a disease with good and poor prognostic subtypes. Dedifferentiated endometrial carcinoma (DEC), undifferentiated endometrial carcinoma (UEC), and clear cell endometrial carcinoma (CEC) are rare high-grade tumors, associated with a poor prognosis and high pathologic stage. Many studies have been performed on the programmed death-ligand 1 (PD-L1) axis mainly focus on endometrioid adenocarcinomas and little research has been done on rare subtypes. The present body of work aims to evaluate the role of indoleamine-2,3-dioxygenase (IDO-1) and stromal differentiation (SD), their correlation with clinicopathologic features and overall survival. Here we found that positive IDO-1 expression in immune cells correlated with worse disease-free survival ( p = 0.02), recurrence ( p = 0.03), high pathologic tumor stage ( p = 0.024), lymph node metastasis ( p = 0.028), and myometrial invasion ( p = 0.03). Our findings suggest IDO-1 to be relevant in both MMR intact and deficient tumors; however, >20% immune cell staining was restricted to MMR deficient cancers. For the stroma, immature, myxoid differentiation was found to correlate with worse disease-free survival ( p = 0.04). We also found the correlation between IDO-1 expression and immature stroma. Looking forward, IDO-1 could be promising for immunotherapy and SD could be the answer to clinical heterogeneity.

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Disease Free Survival of Stage I Endometrial Cancer after Surgery with or without Adjuvant Treatment

Folia Medica Indonesiana ◽

10.20473/fmi.v55i1.12553 ◽

2019 ◽

Vol 55 (1) ◽

pp. 37

Author(s):

Woraluk Moradokkasem ◽

Nungrutai Saeaib ◽

Tippawan Liabsuetrakul

Keyword(s):

Endometrial Cancer ◽

Adjuvant Treatment ◽

Disease Free Survival ◽

Myometrial Invasion ◽

Stage I ◽

Rank Test ◽

Free Survival ◽

Factors Associated ◽

Disease Free ◽

Better Than

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Outcomes and relapse patterns of stage IB grade 2 or 3 endometrial cancer treated with adjuvant vaginal brachytherapy

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2019-000675 ◽

2019 ◽

Vol 30 (1) ◽

pp. 48-55 ◽

Cited By ~ 1

Author(s):

Alexandra Hochreiter ◽

Jacqueline R Kelly ◽

Melissa Rasar Young ◽

Babak Litkouhi ◽

Jonathan David Black ◽

...

Keyword(s):

Risk Factors ◽

Overall Survival ◽

Endometrial Cancer ◽

Disease Free Survival ◽

Myometrial Invasion ◽

Lower Uterine Segment ◽

Pelvic Recurrence ◽

Free Survival ◽

Stage Ib ◽

Disease Free

IntroductionRisk factors for pelvic recurrence in early stage endometrial cancer are poorly understood. We sought to describe outcomes, patterns of failure, and risk factors for recurrence among patients with grade 2–3 endometrial cancer with deep myometrial invasion who were treated with vaginal brachytherapy as sole adjuvant therapy after hysterectomy and lymph node dissection.MethodsWe retrospectively reviewed the records of stage I patients with grade 2–3 endometrioid histology and ≥50% myometrial invasion treated at an academic institution from January 2005 to December 2017. Only patients with endometrioid histology were included. Mixed histologies, including papillary serous or clear cell components, were excluded. Further exclusion criteria were International Federation of Gynecology and Obstetrics stage IB grade 1 patients, follow-up time less than 3 months, receipt of pelvic irradiation or any form of systemic therapy (chemotherapy, aromatase inhibitor). Overall survival, disease-free survival, and pelvic recurrence-free survival were calculated with Kaplan–Meier methods. Multivariable Cox proportional hazards regression was used to analyze factors associated with overall survival and disease-free survival.ResultsAmong 131 consecutive patients identified, 111 (85%) patients met the inclusion criteria. The majority (98.2%) underwent lymph node dissection with ≥10 lymph nodes removed in 78.9%. With a median follow-up of 36 months (IQR 12–70 months), the 3-year overall survival, disease-free survival, and pelvic recurrence-free survival were 89.6%, 90.1%, and 92.8%, respectively. Histologic grade 3, older age, and lymphovascular invasion were not associated with inferior outcomes; however, lower uterine segment involvement (p=0.031), tumor size >4 cm (p=0.024), and <10 lymph nodes removed (p=0.032) were associated with reduced disease-free survival on multivariable analysis. Pelvic recurrence occurred in 12 (11%) patients, most often in the setting of synchronous distant disease (n=9), and was significantly more likely with lower uterine segment involvement.ConclusionAmong patients with stage IB grade 2–3 endometrial cancer treated with vaginal brachytherapy, the risk factors for recurrence (larger tumor size and lower uterine segment involvement) in conjunction with established risk factors (high grade, ≥50% myometrial invasion, and lymphovascular invasion) may identify a group of high-risk patients who might benefit from pelvic radiotherapy.

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Circulating tumor DNA as a prognostic marker in high-risk endometrial cancer

Journal of Translational Medicine ◽

10.1186/s12967-021-02722-8 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Weiwei Feng ◽

Nan Jia ◽

Haining Jiao ◽

Jun Chen ◽

Yan Chen ◽

...

Keyword(s):

Endometrial Cancer ◽

High Risk ◽

Tumor Recurrence ◽

Disease Free Survival ◽

Circulating Tumor Dna ◽

Plasma Samples ◽

Free Survival ◽

Tumor Relapse ◽

Disease Free ◽

Tumor Dna

Abstract Background Currently, there is no reliable blood-based marker to track tumor recurrence in endometrial cancer (EC) patients. Liquid biopsies, specifically, circulating tumor DNA (ctDNA) analysis emerged as a way to monitor tumor metastasis. The objective of this study was to examine the feasibility of ctDNA in recurrence surveillance and prognostic evaluation of high-risk EC. Methods Tumor tissues from nine high-risk EC patients were collected during primary surgery and tumor DNA was subjected to next generation sequencing to obtain the initial mutation spectrum using a 78 cancer-associated gene panel. Baseline and serial post-operative plasma samples were collected and droplet digital PCR (ddPCR) assays for patient-specific mutations were developed to track the mutations in the ctDNA in serial plasma samples. Log-rank test was used to assess the association between detection of ctDNA before or after surgery and disease-free survival. Results Somatic mutations were identified in all of the cases. The most frequent mutated genes were PTEN, FAT4, ARID1A, TP53, ZFHX3, ATM, and FBXW7. For each patient, personalized ddPCR assays were designed for one-to-three high-frequent mutations. DdPCR analysis and tumor panel sequencing had a high level of agreement in the assessment of the mutant allele fractions in baseline tumor tissue DNA. CtDNA was detected in 67% (6 of 9) of baseline plasma samples, which was not predictive of disease-free survival (DFS). CtDNA was detected in serial post-operative plasma samples (ctDNA tracking) of 44% (4 of 9) of the patients, which predicted tumor relapse. The DFS was a median of 9 months (ctDNA detected) versus median DFS undefined (ctDNA not detected), with a hazard ratio of 17.43 (95% CI, 1.616–188.3). The sensitivity of post-operative ctDNA detection in estimating tumor relapse was 100% and specificity was 83.3%, which was superior to CA125 or HE4. Conclusions Personalized ctDNA detection was effective and stable for high-risk EC. CtDNA tracking in post-operative plasma is valuable for predicting tumor recurrence.

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Features associated with survival and disease-free survival in early endometrial cancer

International Journal of Gynecology & Obstetrics ◽

10.1016/0020-7292(90)90770-l ◽

1990 ◽

Vol 31 (2) ◽

pp. 209-210

Author(s):

GP Sutton ◽

HE Geisler ◽

FB Stehman ◽

PCM Young ◽

TM Kimes ◽

...

Keyword(s):

Endometrial Cancer ◽

Disease Free Survival ◽

Free Survival ◽

Disease Free

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Expression of L1CAM and KI-67 in Endometrial Cancer of Egyptian Females: Clinical Impact and Survival

Tumori Journal ◽

10.1177/0300891620914173 ◽

2020 ◽

Vol 106 (1_suppl) ◽

pp. 36-36

Author(s):

Fatma Gharib ◽

Dareen Abd elaziz mohamed ◽

Basma Saed Amer

Keyword(s):

Endometrial Cancer ◽

Endometrial Adenocarcinoma ◽

Univariate Analysis ◽

Disease Free Survival ◽

Rank Test ◽

Significant Heterogeneity ◽

Ki 67 ◽

Free Survival ◽

Disease Free ◽

L1cam Expression

Introduction: Endometrial adenocarcinoma is characterized by a good prognosis. However, the disease response shows a significant heterogeneity. Treatment of endometrial cancer (EC) is still based on clinico-pathological parameters, which have limited role in risk stratification. There is a need for more determinant markers, such as L1 Cell Adhesion Molecule (L1CAM), to identify patients at higher risk of relapse and tailor a more convenient treatment. L1CAM has a capacity to enhance cell motility and promote tumor invasion in different malignancies. In Egypt, the incidence rate of EC is growing over time. Especially in Elgharbiah governorate (home of this study). L1CAM expression and Ki-67 was reported and compared with other clinico-pathological criteria. Method: Seventy-six female patients of endometrial carcinomas were involved in this prospective study. The patients were treated and followed up at Tanta University Hospitals in the period between January 2015 to April 2019. L1CAM expression and Ki-67 was detected by immuno-histochemical exam and compared with other clinico-pathological criteria. Survival was assessed and compared by Kaplan-Meier curves and log-rank test. Results: Positive L1CAM expression was detected in 17 patients (22.4%) and was significantly correlated with unfavorable prognostic factors such as higher stage and grade ( P= 0.021 and P =0.001 respectively), lympo-vascular invasion ( P <0.001), non-endometroid type ( P <0.027) and Ki-67 ( P= 0.003). Univariate analysis revealed that: positive L1CAM; higher tumor grade; high stage; and non-endometrioid type were significantly associated with shorter disease-free survival (DFS) but no significant correlation was detected between Ki-67 and DFS. In multivariate analysis, positive L1CAM remained statistically significant with DFS [P =0.045; 95%CI (1.028:11.17); HR=3.38]. Conclusion: Our study indicates that L1CAM expression and Ki-67 are significantly associated with poor tumor characteristics. L1CAM is significantly associated with shorter disease-free survival and may be a helpful tool as a part of a simple clinical molecular classification for EC.

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Prospective Cohort Study of Pre- and Postdiagnosis Physical Activity and Endometrial Cancer Survival

Journal of Clinical Oncology ◽

10.1200/jco.20.01336 ◽

2020 ◽

Vol 38 (34) ◽

pp. 4107-4117

Author(s):

Christine M. Friedenreich ◽

Linda S. Cook ◽

Qinggang Wang ◽

Renée L. Kokts-Porietis ◽

Jessica McNeil ◽

...

Keyword(s):

Physical Activity ◽

Overall Survival ◽

Endometrial Cancer ◽

Cohort Study ◽

Disease Free Survival ◽

Activity Levels ◽

Recreational Physical Activity ◽

Free Survival ◽

Physical Activity Levels ◽

Disease Free

PURPOSE The aim of this study was to evaluate associations between pre- and postdiagnosis physical activity and survival in survivors of endometrial cancer by physical activity domain, intensity, dose (metabolic-equivalent task [MET]-hours/week/year), and change from pre- to postdiagnosis. METHODS We conducted a prospective cohort study in Alberta, Canada, of 425 women who were diagnosed with histologically confirmed invasive endometrial cancer between 2002 and 2006 and observed to 2019. The interviewer-administered Lifetime Total Physical Activity Questionnaire recorded prediagnosis (assessed at a median of 4.4 months after diagnosis) and postdiagnosis physical activity (assessed at a median of 3.4 years after diagnosis). Associations between physical activity and overall and disease-free survival were assessed using Cox proportional hazards models adjusted for age, stage, grade, treatments, body mass index, menopausal status, hormone therapy use, family history of cancer, and comorbidities. RESULTS After a median follow-up of 14.5 years, there were 60 deaths, including 18 endometrial cancer deaths, and 80 disease-free survival events. Higher prediagnosis recreational physical activity was statistically significantly associated with improved disease-free survival (> 14 v ≤ 8 MET-hours/week/year; hazard ratio [HR], 0.54; 95% CI, 0.30 to 0.96; Ptrend = .04), but not overall survival (HR, 0.56; 95% CI, 0.29 to 1.07; Ptrend = .06). Higher postdiagnosis recreational physical activity (> 13 v ≤ 5 MET-hours/week/year) was strongly associated with both improved disease-free survival (HR, 0.33; 95% CI, 0.17 to 0.64; Ptrend = .001) and overall survival (HR, 0.33; 95% CI, 0.15 to 0.75; Ptrend = .007). Participants who maintained high recreational physical activity levels from pre- to postdiagnosis also had improved disease-free survival (HR, 0.35; 95% CI, 0.18 to 0.69) and overall survival (HR, 0.43; 95% CI, 0.20 to 0.94) compared with those who maintained low physical activity levels. CONCLUSION Recreational physical activity, especially postdiagnosis, is associated with improved survival in survivors of endometrial cancer.

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