Prognosis Of Endometrial Cancer Research Articles

Expression and prognostic value of miRNA-29b in peripheral blood for endometrial cancer.

We explored the role of miR-29b expression in endometrial cancer (EC) progression and patient prognosis. Patients with primary or metastatic EC (n=356), patients with endometrial benign tumors (n=149) and healthy female subjects (n=155) were collected. We assessed the diagnostic value of miR-29b expression for EC using a receiver operating characteristic curve. The miR-29b expressions were lower in patients with primary or metastatic EC. Using miR-29b expression to diagnose EC produced 0.976 area under the curve, 96.1% sensitivity and 97.9% specificity. Cox proportional hazard regression model verified a low miR-29b expression and is an unfavorable prognostic indicator for EC. We conclude that downregulated miR-29b expression correlates with poor EC prognosis and is helpful to evaluate the EC prognosis.

Computational development of a molecular-based approach to improve risk stratification of endometrial cancer patients.

Histological classification and staging are the gold standard for the prognosis of endometrial cancer (EC). However, in morphologically intermediate and doubtful cases this approach results largely insufficient, defining the need for better classification criteria.In this work we developed an algorithm that based on EC genetic alterations and in combination with the current histological classification, improves EC patients prognostic stratification, in particular in doubtful cases. A panel of 26 cancer related genes was analyzed in 89 EC patients and somatic functional mutations were investigated in association with different histology and outcome.An unsupervised hierarchical clustering analysis revealed that two groups of patients with different tumor grade and different prognosis can be distinguished by mutational profile. In particular, the mutational status of APC, CTNNB1, PIK3CA, PTEN, SMAD4 and TP53 resulted to be principal drivers of prognostic clustering. Consistently, a decisional tree generated by a data mining approach summarizes the consequential molecular criteria for patients prognostic stratification.The model proposed by this work provides the clinician with a tool able to support the prognosis of EC patients and consequently drives the choice of the most appropriated therapeutic strategy and follow up.

Exploration of DNA methylation markers for diagnosis and prognosis of patients with endometrial cancer

ABSTRACTThe accurate diagnosis of endometrial cancer (EC) holds great promise for improving its treatment choice and prognosis prediction. This work aimed to identify diagnostic biomarkers for differentiating EC tumors from tumors in other tissues, as well as prognostic signatures for predicting survival in EC patients. We identified 48 tissue-specific markers using a cohort of genome-wide methylation data from three common gynecological tumors and their corresponding normal tissues. A diagnostic classifier was constructed based on these 48 CpG markers that could predict cancerous versus normal tissue with an overall correct rate of 98.3% in the entire repository. Fifteen CpG markers associated with the overall survival (OS) and development of EC were also identified based on the methylation patterns of the EC samples. A prognostic model that aggregated these prognostic CpG markers was established and shown to have a higher discriminative ability to distinguish EC patients with an elevated risk of mortality than the FIGO staging system and several other clinical prognostic variables. This study presents the utility of DNA methylation in identifying biomarkers for the diagnosis and prognosis of EC and will help improve our understanding of the underlying mechanisms involved in the development of EC.

High Expression of Ubiquitin C-terminal Hydrolase L1 Is Associated With Poor Prognosis in Endometrial Cancer Patients.

The ubiquitin C-terminal hydrolase L1 (UCHL1) plays a key role in tumor invasion and metastasis. Ubiquitin C-terminal hydrolase L1 is overexpressed in various cancers and reported to be correlated with a poor prognosis. The objective of this study was to determine the prognostic significance of UCHL1 in endometrial cancer. The expression of UCHL1 in endometrial cancer was assessed using quantitative reverse transcription polymerase chain reaction and immunohistochemistry in 56 and 215 resected tumor specimens, respectively. The 4-year survival rates of the high UCHL1 messenger RNA expression group and high UCHL1 protein expression group were 78% and 71%, respectively, compared with 96% and 95% for the low UCHL1 messenger RNA expression group and low UCHL1 protein expression group, respectively. Kaplan-Meier and log-rank tests indicated a significant correlation between expression of UCHL1 and disease-free survival and overall survival. Moreover, multivariate stepwise Cox proportional hazard regression model analysis showed that UCHL1 was a significant independent marker for predicting a poor disease-free survival and overall survival. In 43 patients with metastatic lesions, immunohistochemical analysis of metastatic lesions revealed that the recurrence rate and mortality rate were 62% and 41%, respectively, in 29 UCHL1-positive patients and 36% and 29%, respectively, in 14 UCHL1-negative patients. The results of this study suggest that high UCHL1 expression is a strong marker of poor prognosis of endometrial cancer. Furthermore, we suggest that UCHL1 may be involved in the development of distant metastasis in endometrial cancer.

Loss of RUNX3 is significantly associated with advanced tumor grade and stage in endometrial cancers.

Loss of runt-related transcription factor 3 (RUNX3) has been reported in various cancers, and one of the mechanisms mediating loss of RUNX3 expression is DNA methylation. However, the role of RUNX3 expression and its DNA methylation status as prognostic factors in endometrial cancer remain unclear. In the present study, the expression and promoter methylation of RUNX3 was examined in endometrial cancer tissues and cell lines, as well as their association with endometrial cancer prognosis. Fifty-five endometrial cancer tissues and two endometrial cancer cell lines (HEC1-α and Ishikawa) were studied. RUNX3 expression and promoter methylation were examined using reverse transcription-polymerase chain reaction (RT-PCR), methylation specific PCR (MS-PCR), and immunohistochemical staining. The demethylating agent 5-aza-2′-deoxycytidine (ADC) was used to reverse the methylation of the RUNX3 promoter. Loss of RUNX3 expression was observed in 50.9% (27/53) of endometrial cancer tissues and in the HEC1-α cell line by immunohistochemistry and RT-PCR, respectively. Methylation of the RUNX3 promoter was observed in 62.2% (33/53) of endometrial cancer tissues, 12.5% (1/8) of normal endometrial tissues, and the HEC1-α cell line by MS-PCR. Tumor grade and stage were significantly correlated with loss of RUNX3 expression. The expression of RUNX3 was restored by treatment with ADC and resulted in growth inhibition in HEC1-α cells. The present results suggested that methylation may serve a critical role in the silencing of RUNX3 and loss of RUNX3 expression may serve as a prognostic marker in endometrial cancer.

Effect of metformin use on the risk and prognosis of endometrial cancer: a systematic review and meta-analysis

BackgroundPrevious studies have suggested that metformin may be useful for preventing and treating endometrial cancer (EC), while the results have been inconsistent. This systematic review and meta-analysis aimed to investigate the association between metformin use and risk and prognosis of patients with EC.MethodsPubMed, Embase, and the Cochrane Library databases were searched for observational studies evaluating the effect of metformin on EC prevention or treatment. The odds ratio (OR) was used for analyzing risks, and the hazard ratio (HR) was used for analyzing survival outcomes. A random-effects model was used for data analysis.ResultsSeven studies reported data on EC risk. The pooled results suggested that metformin was not significantly associated with a lower risk of EC [OR = 1.05, 95% confidence interval (CI) 0.82–1.35, P = 0.70]. For patients with diabetes, metformin showed no advantage in reducing the EC risk compared with other interventions (OR = 0.99, 95% CI 0.78–1.26, P = 0.95). Further, seven studies were included for survival analysis. The pooled data showed that metformin could significantly improve the overall survival of patients with EC (HR = 0.61, 95% CI 0.48–0.77, P < 0.05) and reduce the risk of EC recurrence (OR = 0.50, 95% CI 0.28–0.92, P < 0.05) Finally, we noted metformin was associated with significantly improving the overall survival of EC patients among diabetes (HR = 0.47; 95%CI 0.33–0.67, P < 0.05).ConclusionsThis meta-analysis did not prove that metformin was beneficial for preventing EC. However, metformin could prolong the overall survival of patients with EC and reduce their risk of cancer relapse.

High TRIM44 expression in endometrial carcinoma is associated with a poorer patient outcome

BackgroundTripartite motif‐containing protein 44 (TRIM44) has been recently identified as a novel oncogene that is overexpressed in several types of human cancers; however, its role in endometrial cancer (EC) remains unknown. The purpose of the current study was to investigate the TRIM44 protein expression and clinicopathological significance of TRIM44 in EC. MethodsParaffin-embedded surgical specimens were collected from 143 patients with EC for the immunohistochemical analysis of TRIM44 expression. Western blotting was performed to evaluate differences in TRIM44 protein expression in EC and normal endometrial tissues. ResultsTRIM44 expression was low in normal tissues and high in EC tissues (P < 0.001). TRIM44 overexpression was significantly associated with the Federation of Gynecology and Obstetrics (FIGO) stage, histological grade, depth of myometrial invasion and lymph node metastasis (P < 0.05). Moreover, TRIM44 expression was an independent prognostic factor for both overall survival and disease-free survival in patients with EC (both P < 0.05). ConclusionsThe present study provides evidence that TRIM44 predicts the risk of development and prognosis of EC, highlighting its potential application as a therapeutic target for this malignancy.

Knowledge of the risk factors and symptoms associated with endometrial cancer in British South Asian and British White women

ObjectiveTo explore differences in the background knowledge of Endometrial Cancer (EC), its risk factors, symptoms and prognosis of Endometrial Cancer (EC) between British White (BW) and British South Asian (BSA) women who had undergone treatment for stage I endometrial cancer within the past 3-years. Study designFace-to-face, semi-structured interviews exploring knowledge; diagnosis; treatment; follow-up; and survivorship were undertaken and analysed using Thematic Analysis. ResultsTwenty-one women were interviewed (13 BW and 8 BSA). BW and BSA women reported similar views, experiences and concerns with regards to EC. Knowledge appeared to differ amongst the two groups with BSA women reporting being more aware that unscheduled vaginal bleeding could be associated with a malignancy but having lower levels of knowledge of the risk factors that can lead to EC, compared to BW women. There was a lack of understanding of the difference between cervical cancer and EC and as a result, many women reported taking reassurance from negative cervical cytology as excluding EC. There was also the misconception amongst some of the women that there was a link between sexual behaviour and EC. Women from both groups used the lay healthcare system to discuss their situation/symptoms, however BSA women reported to have specifically sought out women within their social network who had previously undergone treatment for EC. ConclusionsGreater effort is needed to raise awareness in both the BW/BSA communities of the symptoms associated with EC that should prompt medical review. Educational efforts are required to overcome the reported perception that EC is synonymous with cervical cancer and cannot be detected by cervical screening.

THE THERAPEUTIC CHALLENGE IN SYSTEMIC TREATMENT OF ADVANCED AND RECCURENT ENDOMETRIAL CANCER

More than 300 000 new cases of endometrial cancer (EC) are registered annually in the world. The prognosis for EC is determined by the stage of the disease. In Russia, stage III–IV EC is diagnosed in 16 % of patients, with the mortality rate in the first year of follow-up of 9.2 %. The management of recurrent/metastatic EC remains a challenging clinical problem. Hormone therapy and chemotherapy is effective in 30 % of patients, with median progression-free and overall survival rates of approximately 6 months and 12 months, respectively. The role of targeted therapy in the treatment of EC remains undefined. However, several studies demonstrated that combination of targeted therapy with chemotherapy resulted in significant improvement in overall survival of patients with advanced endometrial cancer. Published data on the study of checkpoint inhibitors for EC have shown promising results, however, further research is required to more completely understand how the immune system recognizes and eradicated cancer.

Overexpression of peroxiredoxin-3 and -5 is a potential biomarker for prognosis in endometrial cancer.

Endometrial cancer is the sixth most common cancer in women worldwide. Peroxiredoxins (PRDXs) are antioxidant enzymes that serve important roles in cell differentiation, proliferation, and apoptosis. In the present study, the potential associations between PRDX expression and endometrial cancer were investigated. The expression levels of various PRDX mRNAs were detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) in endometrial cancer tissues (n=26) and normal endometrial tissues (n=10). Additionally, the expression of PRDX isoforms was immunohistochemically examined in endometrial cancer tissues and adjacent normal endometrial tissues from 42 patients. Finally, the associations between high PRDX expression levels and clinicopathological features were examined in patients with endometrial cancer. Analysis of PRDX expression in endometrial cancer tissues and normal endometrial tissues by semi-quantitative RT-PCR showed that all PRDX isoforms had increased expression in the endometrial cancer tissues compared with that in the normal endometrium, and the differences in the expression levels of PRDX1 and PRDX3 between cancer and normal tissues were statistically significant (P=0.0015 and P=0.0134, respectively). Additionally, analysis of PRDX expression in endometrial cancer and paired normal endometrial tissues by immunohistochemistry showed strong cytoplasmic staining of PRDX3 and PRDX5 in cancer tissues, with high PRDX3 (25/42, 59.5%) and PRDX5 (32/42, 76.2%) appearing more frequently in endometrial cancer than in normal endometrial tissues (P=0.0001 and P=0.0023, respectively). Furthermore, high expression of PRDX5 was associated with advanced-stage endometrial cancer (P=0.0399). Although the 5-year survival rate was marginally higher in patients with low expression of PRDX3 and PRDX5, this result was not statistically significant. In summary, PRDX3 and PRDX5 are highly expressed in endometrial cancer and could be associated with advanced stage and poor prognosis. Therefore, these proteins may potentially be used as prognostic markers for endometrial cancer.

HYPERPLASTIC PROCESSES OF ENDOMETRIUM IN WOMEN OF PERIMENOPAUSAL AGE: CLINICAL ASPECTS OF THE PROBLEM

The aim of the study is to identify the most significant clinical and anamnestic risk factors for the onset and progression of endometrial hyperplastic processes and the development of malignant transformation of endometrium in women of perimenopausal age, with taking into account their importance on the basis of statistical analysis. Methods. Based on Spearman’s correlation analysis and determination the degree of dependence of the development of endometrial cancer (from 0 to 1) on clinical-anamnestic and diagnostic risk factors (risk ratio (RR) in groups), there were obtained coefficients for a mathematical model allowing with the use of the binary logistic regression method predict the risk of the appearance of endometrial cancer. Results. The most clinically and statistically significant risk factors for the progression of the pathological process of the endometrium, having a high RR (greater than 1) and a confidence interval of 95% (p &lt; 0.05), are (in the order of significance): recurrence of the endometrial hyperplastic process, obesity, the pronounced blood flow in Ultrasound with color Doppler mapping, polycystic ovary syndrome, abnormal ovarian formations, infertility (primary and secondary), type 2 diabetes mellitus, combined uterine pathology (myoma and/or adenomyosis), hereditary predisposition to cancer development, hypertension, age of 50 years and older. Conclusion. The tactics of the management and treatment of patients with hyperplastic endometrial processes should be based on the detection of the degree of the risk of the progression of pathological processes and the development of the malignant transformation of the endometrium. The study of the individual prognosis of endometrial cancer in patients with hyperplastic endometrial processes currently is becoming increasingly important due to the need to construct a rational treatment plan of the management and performing the follow-up dispensary observation on the basis of a scientifically justified forecast. Results obtained during our work allowed us identify statistically significant risk factors for the development of endometrial cancer. There were obtained coefficients for the creation a reliable mathematical model. With the use of the method of binary logistic regression, it is possible to calculate the risk of developing cancer and choose an effective management tactic for patients with hyperplastic endometrial processes at the perimenopausal age.

Minichromosome maintenance complex component 6 (MCM6) expression correlates with histological grade and survival in endometrioid endometrial adenocarcinoma.

Minichromosome maintenance complex component 6 (MCM6) is involved in initiating DNA replication and is upregulated during licensed G0 phase of the cell cycle. This early expression permits its labeling of more proliferating cells than those by Ki-67. Here using a cohort of 89 endometrioid adenocarcinoma, we report findings made on the prognostic value of MCM6 based on immunohistochemical labeling index (LI) of the protein in comparison with that of Ki67 as no such information is currently available. Additionally, we examined the prognostic values of these markers based on their mRNA expression using a cohort of uterine corpus endometrial carcinoma (UCEC, n = 307) taken from The Cancer Genome Atlas (TCGA) database. Our evidence indicated the presence of a positive correlation between the LI of MCM6 and the histological grade of endometrioid endometrial adenocarcinoma (grade I, 66.7%; grade II, 75.3%; grade III, 81.4%; p < 0.001) and an inverse correlation between the LI of MCM6 and the overall and progression-free survival (p =0.02 for both). The LI of Ki-67 correlated with grade (p < 0.001), but not survival. The MCM6 and Ki-67 inter-observer intra-class correlation coefficients were excellent: 0.84 (95% confidence interval, 0.83-0.91) and 0.84 (0.77-0.90), respectively. For in silico analyses of the TCGA cohort, both univariate and multivariate Cox analyses (p =0.003 and p = 0.03, respectively) revealed high MCM6 mRNA Z-scores associated with reduced overall survival. This association was absent for Ki-67. MCM6 is thus a highly reproducible marker of poor prognosis in endometrial cancer. Evaluation of MCM6 should thus be considered in daily practice for risk stratification.

Circulating cell-free DNA content as blood based biomarker in endometrial cancer.

BackgroundAltered circulating cell-free DNA (cfDNA) levels are related to cancer development and aggressiveness. Up to now, very few studies have been performed for evaluating cfDNA content in endometrial cancer (EC).MethodsFirst, we measured cfDNA release in blood serum of EC cancer patients collected before surgery and before the beginning of any treatment by SYBR Gold assay and correlated it with tumor aggressiveness. We also assessed the relative mitochondrial cell-free DNA (cfmtDNA) content by qRT-PCR. Next, we correlated cfDNA levels with BMI, age, hypertension and inflammation markers.ResultsCfDNA levels are higher in G2 and G3 compared with G1 EC sera. A significant modulation of cfDNA content was detected in sera from patients with BMI>30 compared with those with BMI<30. We observed a further and significant alteration in cfDNA level in hypertensive patients with G2-G3, but not in G1 EC. Analysis of preoperative neutrophil-to-lymphocyte (NLR) and monocyte-to-lymphocyte (MLR) ratios suggests a contribution of the host response in the altered cfDNA levels in EC.ConclusionsOur data indicate that assessment of total and mitochondrial cfDNA levels in blood sera and the relative NLR and MLR in blood obtained from preoperative patients may help clinical management and prognosis in EC.

Estradiol metabolites as biomarkers of endometrial cancer prognosis after surgery

Endometrial cancer (EC) is the most common gynecologic malignancy prevailing after menopause. Defining steroid profiles may help predict the risk of recurrence after hysterectomy, which remains limited due to the lack of reliable markers. Adrenal precursors, androgens, parent estrogens and catechol estrogen metabolites were measured by mass spectrometry (MS) in preoperative serums and those collected one month after hysterectomy from 246 newly diagnosed postmenopausal EC cases. We also examined the associations between steroid hormones and EC status by including 110 healthy postmenopausal women. Steroid concentrations were analyzed in relation to clinicopathological features, recurrence and overall survival (OS). The mean follow-up time was 65.5 months and 26 patients experienced relapse after surgery for a recurrence incidence of 10.6% (6.4% Type I and 29.5% Type II). Recurrence and OS were related to a more aggressive disease but not linked to body mass index. Preoperative levels of estriol (E3) and estrone-sulfate (E1-S) were inversely associated with recurrence in a multivariate logistic regression analysis (Hazard ratios (HRs) of 0.31, P=0.039 and 3.01, P=0.024; respectively). All circulating steroids declined considerably after surgery almost reaching those of healthy women, except 4-methoxy-E2 (4MeO-E2) for which postoperative levels increased by 35% and were associated to a 68% decreased risk of recurrence (HR=0.32, P=0.015). Women diagnosed with both histological types of EC present significantly higher levels of steroids, in support of their mitogenic effects. The estrogen precursor E1-S, the anticancer metabolite 4MeO-E2, and E3 that exert mixed antagonist and agonist estrogenic activities and immunological effects, are potential independent prognostic factors.

Cause-specific mortality in endometrioid endometrial cancer patients with type 2 diabetes using metformin or other types of antidiabetic medication.

To obtain further evidence of the association between metformin or other types of antidiabetic medication (ADM) and mortality from endometrial cancer (EC) and other causes of death in patients with endometrioid EC and type 2 diabetes (T2D). A retrospective cohort of women with existing T2D and diagnosed with endometrioid EC from 1998 to 2011, obtained from a nationwide diabetes database (FinDM), were included in the study. Cumulative mortality from EC and that from other causes was described by using the Aalen-Johansen estimator. Cause-specific mortality rates were analyzed by using Cox models, and adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs) were estimated in relation to the use of different forms of ADM during the three-year period preceding EC diagnosis. From the FinDM cohort we identified 1215 women diagnosed with endometrioid EC, of whom 19% were metformin users, 12% were users of other types of oral antidiabetic medication, 25% used other types of oral antidiabetic medication plus metformin, 26% used insulin and 14% had no antidiabetic medication. Mortality from EC was not found to be different in women using metformin (HR 0.89, 95% Cl 0.52-1.54) but mortality from other causes was lower (HR 0.52, 95% Cl 0.31-0.88) compared with women using other types of oral ADM. Our findings are inconclusive as to the possible effect of metformin on the prognosis of endometrioid EC in women with T2D. However, use of metformin may reduce mortality from other causes.

The influence of vascular endothelial growth factor-A and matrix metalloproteinase-2 and -9 in angiogenesis, metastasis, and prognosis of endometrial cancer.

Angiogenesis (the growth of new blood vessels) is essential in most of the body’s physiological processes, such as in the normal functioning of the endometrium during and after the menstrual cycle. Vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP) are the mostly expressed angiogenic factors, especially, during the process of endometrial degeneration and remodeling. In carcinogenesis, tumor hypoxia-induced factors, through the process of “angiogenic switch”, stimulate the production of angiogenic factors, particularly VEGF and MMP. Subsequently, these angiogenic factors are associated with degradation, differentiation, proliferation, and migration of vascular endothelial cells, enhancing the formation of new blood vessels to supply the tumor with oxygen and nutrients. This process is equally significant for tumor development and metastasis. Hence, like in other cancers, the overexpression of MMP and VEGF in endometrial cancer (EC) seems to play a significant role in its tumorigenesis and metastasis. This research will discuss the influence of MMP and VEGF on angiogenesis, metastasis, and the prognosis of EC as well as the clinical importance of the factors in the diagnosis of EC.

Analysis of endometrial carcinoma in young women at a high-volume cancer center

ObjectiveTo investigate the clinicopathological characteristics, treatment, survival, and prognosis of endometrial cancer in women aged ≤40 years. MethodsWomen who underwent surgery for endometrial cancer at a single high-volume cancer center between January 1995 and December 2014 were retrospectively reviewed. Women aged >40, patients with missing data, and those who did not undergo surgical staging were excluded. Univariate and multivariate regression models were used to identify the risk factors for overall survival and progression-free survival. ResultsA total of 40 patients with endometrial cancer were assessed. The median age at diagnosis was 38 (range, 21–40) years, and most of the uterine tumors found were early-stage (85%), low-grade (67.5%), and endometrioid carcinomas (97.5%). The median serum cancer antigen 125 level was 10.9 IU/mL (range, 3–1284 IU/mL). Optimal cytoreductive surgery was achieved in 35 patients (87.5%). All patients underwent total abdominal hysterectomy, and 97.5% of the patients underwent hysterectomy plus bilateral salpingo-oophorectomy. Among the total group of 40 patients, 21 (52.5%) underwent pelvic and para-aortic lymph node dissection, and 15 (37.5%) underwent only pelvic lymph node dissection. Multivariate analysis confirmed that a cancer antigen 125 level ≥35 was the only independent prognostic factor for both progression-free survival (hazard ratio, 22.997; 95% confidence interval, 1.783–296.536; p = 0.016) and overall survival (hazard ratio, 22.541; 95% confidence interval, 1.75–290.364; p = 0,017). ConclusionsOur study demonstrated that a cancer antigen 125 level ≥ 35 is the only independent prognostic factor for both progression-free survival and overall survival in patients aged ≤40 years with endometrial cancer.

Expression of CD44 variant 6 and its prognostic value in benign and malignant endometrial tissue.

CD44 expression in both the early and metastatic phases of many epithelial and non-epithelial cancers is strongly prognostic. The objective of the study is to evaluate whether there is any relationship between the expression of CDD44v6 and endometrial cancer (EC) staging and prognosis. This retrospective study included 60 EC patients for whom surgical staging was performed between 2000 and 2006. Twenty-eight randomly selected patients with normal endometria served as the control group. We immunohistochemically evaluated membranous and cytoplasmic CD44v6 staining in tissue paraffin blocks. The results were graded as positive or negative. Membranous staining in both advanced and early stage EC patients was significantly higher than that in the control group (p=0.002). The extent of either membranous or cytoplasmic staining in both advanced- and early stage patients did not differ significantly by age, tumor grade, stage, extent of myometrial invasion, lymph node involvement, cytology, adnexal involvement, or omental spreading. In advanced-stage patients, neither papillary serous not clear cell cancers exhibited cytoplasmic staining. CD44v6 membranous staining can be useful for differentiating malignant from benign endometrial tissue. However, staining is not associated with EC staging or prognosis.

A New Diagnostic and Prognostic Marker in Endometrial Cancer: Neopterin.

In this study, we investigated the correlation between serum and urinary neopterin levels as well as the stage of the disease in women with endometrial cancer.Increased neopterin concentrations are reported in patients with activation of macrophages by interferon-γ, which includes the following: viral infections, autoimmune disorders, allograft rejection, and various malignant tumors. In patients with several types of cancer, high-neopterin concentrations in body fluids like serum/plasma, urine, ascites, and cerebrospinal fluid indicate the course of the disease, and it is associated with poor prognosis. In the light of foregoing, we aimed to investigate the role of neopterin as a prognostic biomarker in endometrial cancer. Serum neopterin concentrations were determined by enzyme-linked immunosorbent assay and urinary neopterin by high-performance liquid chromatography in 41 patients with endometrial cancer (group 2) and 41 healthy women (group 1). Increased urinary neopterin levels were observed in patients with endometrial cancer (P < 0.001), and the difference in the urinary neopterin levels between low and high stages of endometrial cancer was significant (P < 0.01; stage I-II vs stage III-IV, respectively). Serum neopterin levels did not show a significant difference in each group. This study suggests that urinary neopterin levels are relevant in evaluating the endometrial cancer stage and follow-up of the disease. As a result, using neopterin and cancer antigen 125 together would be useful in determining the prognosis of endometrial cancer and its posttreatment progression.

Sox2-dependent inhibition of p21 is associated with poor prognosis of endometrial cancer.

Sex‐determining region Y‐box 2 (SOX2) is an essential factor involved in the self‐renewal and pluripotency of embryonic stem cells and has functions in cell survival and progression in many types of cancers. Here, we found that several endometrial cancer cell lines expressed SOX2, which was required for cell growth. Additionally, SOX2 overexpression regulated the expression of cyclin‐dependent kinase inhibitor 1A (CDKN1A), and SOX2 specifically bound to p21 promoter DNA in endometrial cancer cell lines expressing SOX2. Expressions of SOX2 in endometrial cancer patients were significantly correlated with histological grade and poor prognosis. Moreover, low p21 together with high SOX2 expressions in advanced endometrial cancer patients were associated with the most unfavorable outcomes of patients. These results indicated that simultaneous measurement of SOX2 and p21 expression in endometrial cancer patients may be a useful biomarker for patient prognosis.