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

2018 ◽  
Vol 28 (3) ◽  
pp. 505-513 ◽  
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.

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

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.

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

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.

LAPTM4B-35 Overexpression Is an Independent Prognostic Marker in Endometrial Carcinoma

2010 ◽  
Vol 20 (5) ◽  
pp. 745-750 ◽  
Author(s):  
Fan-ling Meng ◽  
Ming-zhu Yin ◽  
Hong-tao Song ◽  
Hua Yang ◽  
Ge Lou ◽  
...  
Keyword(s):  
Overall Survival ◽  
Endometrial Carcinoma ◽  
Cancer Progression ◽  
Histological Grade ◽  
Disease Free Survival ◽  
Myometrial Invasion ◽  
Normal Endometrium ◽  
Free Survival ◽  
Gynecology And Obstetrics ◽  
Disease Free

Background:Lysosomal protein transmembrane 4 β-35 (LAPTM4B-35), a novel oncoprotein that belongs to the mammalian 4-tetratransmembrane spanning protein superfamily, has been implicated in oncogenesis and cancer progression in several solid malignances. However, the expression of LAPTM4B-35 and its role in endometrial cancer progression remain unknown.Materials and Methods:We investigated the expression of the LAPTM4B-35 protein by immunohistochemistry in 30 normal endometrium specimens and 165 endometrial carcinomas and analyzed its correlation with various clinicopathologic features, including patient outcome.Results:LAPTM4B-35 immunoreactivity was overexpressed in endometrial carcinoma cases compared with normal endometrium (P < 0.001). High LAPTM4B-35 expression was found in 117 (70.91%) of these 165 carcinomas and was positively correlated with the International Federation of Gynecology and Obstetrics stage, histological grade, depth of myometrial invasion, lymph node metastasis, lymph vascular space involvement, and recurrence, but not with age and histological type. Patients with high LAPTM4B-35 expression had significantly poorer overall survival and disease-free survival compared with patients with low expression of LAPTM4B-35 (P = 0.001 and P = 0.002, respectively). Multivariate analysis showed that high LAPTM4B-35 expression was an independent prognostic factor for both overall survival and disease-free survival of patients with endometrial carcinoma (both P = 0.005).Conclusions:These results showed that high LAPTM4B-35 expression was associated with progression and prognosis of endometrial carcinoma.

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

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5594-5594
Author(s):  
Martin Ore ◽  
Ignacio Romero ◽  
Zaida Garcia-Casado ◽  
Cristina Zorrero ◽  
Carmen Illueca ◽  
...  
Keyword(s):  
Immune Response ◽  
Endometrial Cancer ◽  
Disease Free Survival ◽  
Myometrial Invasion ◽  
Lower Grade ◽  
Roc Curve Analysis ◽  
Free Survival ◽  
Hematoxylin And Eosin ◽  
Infiltrating Lymphocytes ◽  
Disease Free

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]

scholarly journals Stage IB Endometrioid Type Endometrial Cancer: The Role of Lymphadenectomy and Adjuvant Radiation Therapy

2018 ◽  
Vol 24 (3) ◽  
pp. 156
Author(s):  
Osman Turkmen ◽  
Tolga Tasci ◽  
Derman Basaran ◽  
Gunsu Comert Kimyon ◽  
Alper Karalök ◽  
...  
Keyword(s):  
Overall Survival ◽  
Endometrial Cancer ◽  
Adjuvant Radiotherapy ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Adjuvant Radiation ◽  
Free Survival ◽  
Stage Ib ◽  
Gynecology And Obstetrics ◽  
Disease Free

<p><strong>Objective:</strong> Both performances of lymphadenectomy and benefit of adding adjuvant radiotherapy are controversial for patients with International Federation of Gynecology and Obstetrics stage IB endometrioid type endometrial cancer. We aimed to identify the role of lymphadenectomy and adjuvant radiation therapy as well as clinicopathological prognostic factors for this group of patients.<br /><strong></strong></p><p><strong>Study Design:</strong> Records of all patients (n=132) with stage IB endometrioid endometrial cancer who were referred to or treated in our institution between Jan 1992 and Dec 2013 were retrospectively reviewed. Cox Proportional Hazard Regression Analysis was used to determine the effects of lymphadenectomy and adjuvant radiation as well as other clinicopathological factors on disease free survival and overall survival.</p><p><strong>Results:</strong> Mean age was 59.9 years (range, 45-82). Lymphadenectomy didn't perform in 36 (27.3%) patients and 23 (17.4%) patients did not have any kind of adjuvant treatment. Mean lymph node count was 18.8 (range, 3-67). Federation of Gynecology and Obstetrics grade, lymphovascular space invasion, lymphadenectomy, receiving adjuvant treatment and type of received adjuvant therapy were not associated with disease free survival and overall survival for the entire cohort. In a subgroup of patients with grade1&amp;2 tumor, 5-year disease free survival rates were 80% and 50% (p=0.4), respectively and overall survival rates were 94.8% and 93.8% (p=0.2), respectively for patients who had or didn't have adjuvant radiotherapy. While performance of lymphadenectomy was not significantly associated with disease free survival in this subgroup (p=0.56), this association was statistically significant for overall survival (97.9% vs. 86.4%, p=0.04) <br /><strong></strong></p><p><strong>Conclusion:</strong> Benefit of adjuvant radiotherapy in regard to prevention of recurrence needs to be confirmed by further studies. Lymphadenectomy had a survival benefit for patients with myometrial invasion greater than a half of myometrial thickness.</p>

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

2020 ◽  
Author(s):  
Weiwei Feng ◽  
Nan Jia ◽  
Hai-ning 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.

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

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
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.

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

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.

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

Rare Tumors ◽  
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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