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.

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.

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.

Expression of the retinoblastoma-related gene Rb2/p130 correlates with clinical outcome in endometrial cancer.

1998 ◽  
Vol 16 (3) ◽  
pp. 1085-1093 ◽  
Author(s):  
T Susini ◽  
F Baldi ◽  
C M Howard ◽  
A Baldi ◽  
G Taddei ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Clinical Outcome ◽  
Endometrial Carcinoma ◽  
Tumor Cells ◽  
Disease Free Survival ◽  
Tumor Stage ◽  
Related Gene ◽  
Increased Risk ◽  
Disease Free ◽  
Ploidy Status

PURPOSE The retinoblastoma gene is the prototype of tumor-suppressor genes and has been shown to be involved in the pathogenesis and progression of several human malignancies. In this study, we determined the relation between the expression of a newly discovered retinoblastoma-related gene Rb2/p130 and outcome in patients with endometrial carcinoma. PATIENTS AND METHODS pRb2/p130 expression was determined immunohistochemically in specimens of endometrial carcinoma (stages I to IV) from 100 patients who underwent surgery as the first treatment. The pRb2/p130 status was analyzed in relation to the length of disease-free survival and disease-specific survival. RESULTS Decreased levels of pRb2/p130 in endometrial cancer cells was significantly associated with a decreased probability of remaining disease-free after treatment (P = .003) and with decreased probability of survival (P < .0001). In a multivariate analysis, pRb2/p130 status (P = .004), tumor stage (P = .009), and ploidy status (P = .02) were independent predictors of clinical outcome. The risk of dying of disease was increased substantially (risk ratio, 4.91; 95% confidence interval, 1.66 to 14.54) among patients with decreased levels of pRb2/p130 in tumor cells. CONCLUSION In patients with endometrial carcinoma who did not receive radiotherapy or chemotherapy before surgery, the presence of decreased levels of pRb2/p130 in tumor cells is associated with a significantly increased risk of recurrence and death of disease, independent of tumor stage and ploidy status.

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]

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

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

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.

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

2019 ◽  
Vol 30 (1) ◽  
pp. 48-55 ◽  
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.

scholarly journals Correlation of Computed Tomography Parameters with Histology, Stage and Prognosis in Surgically Treated Thymomas

Medicina ◽  
2020 ◽  
Vol 57 (1) ◽  
pp. 10
Author(s):  
Angelo Carretta ◽  
Stefano Viscardi ◽  
Piergiorgio Muriana ◽  
Paola Ciriaco ◽  
Alessandro Bandiera ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Ct Scan ◽  
Disease Free Survival ◽  
Tumor Stage ◽  
Tnm Staging ◽  
Prognostic Role ◽  
Free Survival ◽  
Staging Systems ◽  
Disease Free

Background and objectives: The histological classification and staging of thymic tumors remains a matter of debate. The correlation of computed tomography (CT) parameters with tumor histology and stage also still has to be completely assessed. The aim of this study was therefore to analyze the correlation of radiological parameters with histological and staging classifications of thymomas evaluating their prognostic role. Methods: Data of 50 patients with thymoma submitted to a complete surgical treatment between 2005 and 2015 were retrospectively analyzed. Tumors were classified according to the WHO and Suster and Moran (S&M) histological classifications and to the Masaoka–Koga and tumor, node and metastases (TNM) staging systems. The correlation of CT features with histology and stage and the prognostic role of histopathological and radiological features were assessed. Results: Five-year overall (OS) and disease-free survival (DFS) were 90.3% and 81.1%, respectively. A significant correlation of DFS with the Masaoka–Koga (p = 0.001) and TNM staging systems (p = 0.002) and with the S&M (p = 0.02) and WHO histological classifications (p = 0.04) was observed. CT scan features correlated with tumor stage, histology and prognosis. Moderately differentiated tumors (WHO B3) had a significantly higher incidence of irregular shape and contours (p = 0.002 and p = 0.001, respectively) and pericardial contact (p = 0.036). A larger tumor volume (p = 0.03) and a greater length of pleural contact (p = 0.04) adversely influenced DFS. The presence of pleural (p < 0.001) or lung invasion (p = 0.02) and of pleural effusion (p = 0.004) was associated with a significantly worse OS. Conclusions: Pre-operative CT scan parameters correlate with stage and histology, and have a prognostic role in surgically treated thymomas.

scholarly journals Metastatic Lymph Node Ratio (mLNR) is a Useful Parameter in the Prognosis of Colorectal Cancer; A Meta-Analysis for the Prognostic Role of mLNR

Medicina ◽  
2019 ◽  
Vol 55 (10) ◽  
pp. 673 ◽  
Author(s):  
Pyo ◽  
Kim ◽  
Lee ◽  
Baek ◽  
Kang
Keyword(s):  
Lymph Node Ratio ◽  
Metastatic Lymph Node ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Tumor Stage ◽  
Tumor Location ◽  
Free Survival ◽  
Node Ratio ◽  
Disease Free

Background and objectives: The presenting study aimed to elucidate the prognostic role of the metastatic lymph node ratio (mLNR) in patients with colorectal cancer (CRC), using a meta-analysis. Materials and Methods: Using data from 90,274 patients from 14 eligible studies, we performed a meta-analysis for the correlation between mLNR and survival rate. Besides, subgroup analyses were performed, based on tumor stage, tumor location, and mLNR. Results: A high mLNR showed significant correlation with worse overall survival and disease-free survival rates in CRC patients (hazard ratio (HR), 1.617, 95% confidence interval (CI) 1.393–1.877, and HR 2.345, 95% CI 1.879–2.926, respectively). In patients with stage III, who had regional LN metastasis, the HRs were 1.730 (95% CI 1.266–2.362) and 2.451 (95% CI 1.719–3.494) for overall and disease-free survival, respectively. According to tumor location, rectal cancer showed a worse survival rate when compared to colon cancer. In the analysis for overall survival, when mLNR was 0.2, HR was the highest across the different subgroups (HR 5.040, 95% CI 1.780–14.270). However, in the analysis for disease-free survival, the subgroup with an mLNR < 0.2 had a higher HR than the other subgroups (HR 2.878, 95% CI 1.401–5.912). Conclusions: The mLNR may be a useful prognostic factor for patients with CRC, regardless of the tumor stage or tumor location. Further studies are necessary for the detailed criteria of mLNR before its application in daily practice.

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