Endometrial Carcinoma Patients Research Articles

Pembrolizumab window study: Illuminating the immunologic landscape in gynecologic cancers

Objective: A “window of opportunity” study in newly diagnosed ovarian (OV) and endometrial (EM) carcinoma patients was conducted to assess changes in PD-L1 expression and immune cell recruitment in response to pembrolizumab, a PD-1 inhibitor.

Long Non-Coding RNA SNHG14 Impedes Viability, Migration and Invasion of Endometrial Carcinoma Cells Through Modulating miR-93-5p/ZBTB7A Axis.

BackgroundThe function of long non-coding RNA small nucleolar RNA host gene 14 (SNHG14) in endometrial carcinoma (EC) has not been thoroughly reported. This research is designed to research the action mechanism of SNHG14 in EC development.MethodsThe expression of SNHG14 was estimated in The Cancer Genome Atlas and was verified by qRT-PCR in EC tissues. The correlation between SNHG14 expression and clinicopathological features of EC patients was analyzed. Cell viability, wound healing rate, and relative invasion rate were examined by MTT, wound healing, and transwell assay. StarBase, TargetScan, RNA pull-down, and dual luciferase reporter gene (DLR) assay were conducted to analyze the relationship among SNHG14, miR-93-5p and ZBTB7A.ResultsSNHG14 was underexpressed in EC. SNHG14 expression was significantly relevant to menstruation, FIGO stage, histological grade and lymphatic metastasis of EC patients. SNHG14 overexpression hampered viability, migration and invasion of EC cells. SNHG14 functioned as a sponge for miR-93-5p, and miR-93-5p inhibition restrained cell viability, migration and invasion in EC. In addition, miR-93-5p directly targeted to ZBTB7A, which was underexpressed in EC. The suppressive action of SNHG14 overexpression on the viability, migration and invasion of EC cells was partly rescued by miR-93-5p overexpression or ZBTB7A silencing.ConclusionLncRNA SNHG14 hampered the viability, migration and invasion of EC cells via modulating miR-93-5p/ZBTB7A axis.

LncRNA SNHG14 promotes proliferation of endometrial cancer through regulating microRNA-655-3p.

Previous studies have shown that long non-coding RNA (lncRNA) SNHG14 can act as a cancer-promoting gene, but the role of SNHG14 in the development of endometrial carcinoma (EC) has not been reported. This study was designed to investigate the expression characteristics of SNHG14 in EC tissues and cells and to specify whether SNHG14 promotes the malignant progression of EC by modulating microRNA-655-3P. Quantitative Real Time-Polymerase Chain Reaction (qPCR) was carried out to examine SNHG14 expression in tumor tissue specimens and paracancerous tissue specimens collected from 52 patients with EC, and the relationship between SNHG14 expression and clinical indicators or prognosis of these subjects was analyzed as well. Further, the expression level of SNHG14 in EC cell lines was also verified by qRT-PCR. In addition, SNHG14 knockdown and the overexpression models were constructed using lentivirus in EC cell lines, Ishikawa, and KLE, and the influence of SNHG14 on EC cell biological functions was evaluated by Cell Counting Kit-8 (CCK-8), plate cloning, 5-ethynyl-2'-deoxyuridine (EdU) and flow apoptosis assays. Finally, in vitro recovery experiments were conducted to explore the mechanism by which SNHG14 interacts with microRNA-655-3P to exert its effect on the progression of EC. qPCR results indicated that SHHG14 expression in EC tumor tissues was remarkably higher than that in adjacent tissues. Compared with patients with low expression of SNHG14, patients with high expression of SNHG14 had larger tumor size, lower overall survival, and more advanced pathological stage. In vitro, compared with those in the control group, the overexpression of SNHG14 markedly enhanced EC cell proliferation while inhibited cell apoptosis, and the opposite result was observed in SNHG14 silencing group. Subsequently, qRT-PCR verified that microRNA-655-3P expression was significantly reduced in EC tissues and negatively correlated with SNHG14. In addition, recovery experiment revealed a mutual regulation between SNHG14 and microRNA-655-3P, the two of which may together modulate the malignant progression of EC. EC tumor tissues contain a significantly high expression of LncRNA SNHG14, which has been confirmed to be remarkably associated with tumor size, pathological stage, and poor prognosis of EC patients. Additionally, lncRNA SNHG14 is capable of accelerating malignant progression of EC by regulating microRNA-655-3P expression.

A Modern Approach to Endometrial Carcinoma: Will Molecular Classification Improve Precision Medicine in the Future?

Endometrial cancer has been histologically classified as either an estrogen-dependent cancer with a favorable outcome or an estrogen-independent cancer with a worse prognosis. These parameters, along with the clinical attributions, have been the basis for risk stratification. Recent molecular and histopathological findings have suggested a more complex approach to risk stratification. Findings from the Cancer Genome Atlas Research Network established four distinctive genomic groups: ultramutated, hypermutated, copy-number low and copy-number high prognostic subtypes. Subsequently, more molecular and histopathologic classifiers were evaluated for their prognostic and predictive value. The impact of molecular classification is evident and will be recognized by the upcoming WHO classification. Further research is needed to give rise to a new era of molecular-based endometrial carcinoma patient care.

Identification of a metabolism-related gene expression prognostic model in endometrial carcinoma patients

BackgroundMetabolic abnormalities have recently been widely studied in various cancer types. This study aims to explore the expression profiles of metabolism-related genes (MRGs) in endometrial cancer (EC).MethodsWe analyzed the expression of MRGs using The Cancer Genome Atlas (TCGA) data to screen differentially expressed MRGs (DE-MRGs) significantly correlated with EC patient prognosis. Functional pathway enrichment analysis of the DE-MRGs was performed. LASSO and Cox regression analyses were performed to select MRGs closely related to EC patient outcomes. A prognostic signature was developed, and the efficacy was validated in part of and the entire TCGA EC cohort. Moreover, we developed a comprehensive nomogram including the risk model and clinical features to predict EC patients’ survival probability.ResultsForty-seven DE-MRGs were significantly correlated with EC patient prognosis. Functional enrichment analysis showed that these MRGs were highly enriched in amino acid, glycolysis, and glycerophospholipid metabolism. Nine MRGs were found to be closely related to EC patient outcomes: CYP4F3, CEL, GPAT3, LYPLA2, HNMT, PHGDH, CKM, UCK2 and ACACB. Based on these nine DE-MRGs, we developed a prognostic signature, and its efficacy in part of and the entire TCGA EC cohort was validated. The nine-MRG signature was independent of other clinical features, and could effectively distinguish high- and low-risk EC patients and predict patient OS. The nomogram showed excellent consistency between the predictions and actual survival observations.ConclusionsThe MRG prognostic model and the comprehensive nomogram could guide precise outcome prediction and rational therapy selection in clinical practice.

A prospective multicenter international single-arm observational study on the oncological safety of the sentinel lymph node algorithm in stage I intermediate-risk endometrial cancer (SELECT, SEntinel Lymph node Endometrial Cancer Trial)

BackgroundIn the primary treatment of apparent uterine-confined endometrial carcinoma, pelvic ± para-aortic lymphadenectomy has been considered the standard of care. Although some retrospective data suggest that the sentinel lymph node...

Uterine fibroids may play a protecting role against endometrial carcinoma in Chinese women with gynecological diseases.

Background: It has been reported that uterine fibroids (UFs) may increase the risk of endometrial carcinoma (EC) with the underlying mechanism largely unknown. Here, we explore whether UF could be an influential factor for EC.Methods: We have collected and analyzed clinical data from 4537 Chinese patients to study the co-incidence of UF and EC. Then, a large-scale literature-based data mining was conducted to identify genes implicated as UF downstream regulating targets and EC upstream regulators. In addition, a meta-analysis has been conducted for each of the EC-specific genes, using six independent UF expression datasets. The meta-analysis results, together with literature-based pathway analysis, were used to explore the potential explanation of the clinical data.Results: Our results showed that the incidence rate of EC in the case of UF was 50.53% lower than without UF, which suggested a protective role of UF in EC patients. The meta-analysis identified three significantly overexpressed genes (HTRA3, HOPX, and PCNA) in the case of UF, which were implicated as EC inhibitors in the pathway analysis. Multiple linear regression (MLR) analysis showed that, compared with UF, aging might be a stronger influential factor for EC.Conclusion: Among women with gynecological diseases, UFs may play a protecting role against EC in the Chinese population.

POLE Mutation Characteristics in a Chinese Cohort with Endometrial Carcinoma.

ObjectiveTo study the characteristics of polymerase epsilon (POLE) exonuclease domain mutations in Chinese patients with endometrial carcinoma (EC).MethodsThis study analyzed data from 529 patients with EC in The Cancer Genome Atlas (TCGA) and 467 EC patients evaluated at the Shanghai First Maternity and Infant Hospital (SFMIH). POLE mutation heterogeneity was analyzed in paired curettage and hysterectomy samples from 120 SFMIH patients. Sanger sequencing identified mutations in the POLE exonuclease domain, and correlations between POLE mutation status and various clinicopathological features were determined by chi-squared testing and Cohen’s kappa analysis, with Kaplan–Meier survival curves generated to assess correlations between POLE mutation status and overall survival (OS).ResultsThirty-five mutations were identified in 467 samples (7.5%), and novel mutations were detected in the SFMIH cohort. Compared to the TCGA cohort, the SFMIH cohort had fewer POLE mutations when matched by age (<60) and histology (endometrioid) (p < 0.001 and p = 0.010, respectively). In our study cohort, POLE mutations were significantly associated with adjuvant treatment (p = 0.029), and patients with POLE mutations who underwent chemoradiotherapy had a poor OS (p < 0.0001). Notably, shorter OS was significantly associated with POLE mutations in hysterectomy samples from patients aged >60 years or with stage I disease in the paired curettage-hysterectomy group.ConclusionThe significant difference in POLE mutation profiles between the TCGA and SFMIH cohorts, as well as the poor consistency between the curettage and hysterectomy samples, suggests that different parameters need to be applied to determine the prognosis of patients with EC in China.

LncRNA AFAP1-AS1 contributes to the progression of endometrial carcinoma by regulating miR-545-3p/VEGFA pathway

Endometrial carcinoma (EC) accounts for 20%–30% of female reproductive tumors. Targeted therapy for EC has shown great advantages with small side effects. To improve the survival of EC patients, more new therapeutic targets need to be found. Long non-coding RNAs (lncRNAs) are series of RNAs with over 200 nucleotides that regulate various cellular functions. LncRNA actin filamentin-1 antisense RNA 1 (AFAP1-AS1) is involved in the development of a variety of cancers, such as pancreas ductal adenocarcinoma and esophageal adenocarcinoma. However, it is not clear whether AFAP1-AS1 has any effects on EC or the exact regulatory mechanism. Herein, we found the high expression of AFAP1-AS1 in human EC tissues, and AFAP1-AS1 was correlated with EC patients’ prognosis and clinical features. AFAP-AS1 could affect EC cell proliferation, migration, and invasion, and contributed to endothelial cell angiogenesis. We further showed that AFAP-AS1 could promote the expression of VEGFA through the adsorption of miR-545-3p, thus promoting the angiogenesis and invasion of EC, and contribute to tumor growth and metastasis in vivo. Thus, we thought AFAP1-AS1 had the potential to serve as an EC therapeutic target.

Prognosis Trend of Grade 2 Endometrioid Endometrial Carcinoma: Toward Grade 1 or 3?

Although the prognostic significance of grade in endometrial cancer is well known, grade 2 cases have not been evaluated separately in most of the previous studies. In this study, we aim to investigate whether the oncologic outcomes of grade 2 endometrioid endometrial carcinomas trend towards grade 1 or 3 tumors. Patients' records and pathological reports were reviewed retrospectively and eligible patients with endometrioid endometrial carcinoma were determined and distributed into 3 groups according to their 1988 International Federation of Gynecology and Obstetrics (FIGO) grade. Groups' characteristics and oncologic outcomes were compared. Differences between grades were tested with z-test and adjusted by Bonferroni method. Kaplan-Meier method was performed for the survival analysis. In total, 776 patients of endometrioid endometrial carcinoma were included in this study. Mean follow-up time was 52 ± 14months. Patients' mean age was 56.3 ± 10.8years. Even though grade 2 endometrioid endometrial carcinomas were different from both grade 1 and 3 in terms of the pathological features, survival analyses demonstrated that their oncologic outcomes trended towards grade 1. The grade was determined as an independent prognostic factor for overall survival (OS). The interobserver reproducibility will be improved among pathologists by combining FIGO grade 1 and 2 endometrioid endometrial carcinomas, while prognosis prediction is not likely to be affected.

LINC00565 Enhances Proliferative Ability in Endometrial Carcinoma by Downregulating KLF9.

ObjectiveTo detect LINC00565 expression level in endometrial carcinoma (EC) samples and cell lines, and the correlations between LINC00565 and clinical features of EC patients. After intervening LINC00565, the underlying mechanism about proliferative ability in EC cell lines is observed.MethodsRelative levels of LINC00565 and KLF9 in 52 paired EC and paracancerous tissues were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The relationship between relative level of LINC00565 or KLF9 and clinical features of EC patients was analyzed. After knockdown of LINC00565 and KLF9, potential regulations of them on biological functions of EC were examined by Cell Counting Kit (CCK-8), colony formation assay and in vivo xenograft model in nude mice, respectively. At last, dual-luciferase reporter assay and rescue experiments were conducted to illustrate the mechanisms of LINC00565 and KLF9 in mediating the development of EC.ResultsLINC00565 was upregulated in EC tissues. Chi-square analysis showed that a high level of LINC00565 predicted large tumor size, advanced pathological staging and poor prognosis in EC. Silence of LINC00565 decreased proliferative ability in EC cells and tumor growth in nude mice bearing EC. KLF9 was the target gene of LINC00565. The negative interaction between LINC00565 and KLF9 was responsible for stimulating the malignant development of EC. Knockdown of KLF9 could abolish the regulatory effects of silenced LINC00565 on proliferative ability and tumorigenesis in EC.ConclusionLINC00565 is upregulated in EC tissues and closely linked to tumor size, pathological staging and poor prognosis in EC patients. LINC00565 stimulates proliferative ability in EC by downregulating KLF9.

A Retrospective Mapping of Pelvic Lymph Node Metastasis Distribution in Patients with Endometrial Carcinoma

Systematic removal of pelvic lymph node for endometrial carcinoma has high morbidity. We performed a retrospective analysis of 216 patients with endometrial carcinoma in Peking University First Hospital between January 2001 and March 2017, in order to evaluate the metastasis distribution of pelvic lymph node in patients with endometrial carcinoma. A total of 21 (9.7%) cases had lymph node metastases with an average positive lymph node number of 31.5 per cases. Among the positive group, 10 were obturator vein lymph nodes, 5 were internal iliac lymph nodes, and 5 were external iliac lymph nodes. Three cases of deep inguinal lymph nodes and 1 case of common iliac lymph node metastasis were accompanied by other pelvic lymph node metastases. No independent metastasis of deep inguinal lymph nodes and common iliac lymph node metastasis were detected. We conclude that obturator vein lymph node might be the most common metastasis site of pelvic lymph node with endometrial carcinoma patients.

Clinical outcomes of MSI-high (MSI-H) versus stable (MSS) endometrial carcinoma (EC) after front-line platinum chemotherapy and subsequent matched therapy.

6086 Background: Precision oncology approaches in EC patients (pts) are evolving with emerging targeted therapy. We reviewed the effect of genomic findings on treatment choice and outcome in an Asian EC cohort. Methods: Recurrent or metastatic ECs were prospectively profiled with next-generation sequencing (NGS) and relevant immunohistochemistry. Clinical data were collected to assess outcomes. Results: Between 12/2014 to 12/2019, 51 Asian EC pts of endometrioid (26/51), serous (7/51), carcinosarcoma (4/51), clear cell (4/51) and mixed (10/51) histology were enrolled. 35/51(69%) of tumors were high grade. The median age at diagnosis was 56 (range 37-77), and the median lines of treatment received was 3 (range 1-8). 45/51(88%) of pts had successful NGS profiling, 31/45(69%) using FoundationOne CDx, and 14/45 (31%) on an in-house platform. Frequent mutations (&gt;20%) occurred in PTEN (60%), PIK3CA (49%), TP53 (46%), ARID1A (27%), CTNNB1 (24%) and KRAS (22%). There were 12/51(24%) MSI-H, 25/51(49%) MSS, and 14/51(27%) MSI-unknown tumors. The 6 mth progression free survival (PFS) rate for MSS versus MSI-H pts treated with front-line carboplatin+paclitaxel (CP) was 83% versus 50% (RR 1.67, fisher’s exact 2-sided p=0.09), with a shorter median PFS after 1st line CP for MSI-H versus MSS pts (median 5.2 mth vs. 8.3 mth, not sig). Upon progression, 29/51(57%) of pts were matched to therapy based on tumor profiles. Of these, 7/29(24%), 13/29(45%) and 9/29(31%) matched to anti-PD1/PD-L1, endocrine therapy and other targeted therapy, respectively. Among 7 MSI-H pts matched to anti-PD1/PD-L1 therapy, median PFS was 14.6 mth (95% CI 0.4-29), and objective response rate was 57%(4/7). In subsequent-line, matching to endocrine therapy (HR 4.3 95% CI 0.95-19.0, p=0.06) or other targeted therapy (HR 5.1, 95% CI 1.1-24.5, p=0.04) was associated with worse PFS compared to anti-PD1/PD-L1 therapy. Despite a short median PFS after front-line CP, median overall survival (OS) was not reached for MSI-H pts, compared to 38 mth (95% CI 30.7-46.0) for MSS and MSI-unknown pts. Conclusions: MSI-H EC pts appear to have shorter PFS to front-line CP chemotherapy compared with MSS pts, but may derive durable responses from immunotherapy in subsequent-line therapy. Early use of immunotherapy in advanced MSI-H EC pts should be considered. Further optimisation of therapy is urgently needed in advanced MSS EC.

Treatment Outcomes of Advanced Stage Endometrial Carcinoma (Stage III-IV) and Related Factors

Objective: The aim of this study was to determine treatment response, the recurrence rate, 3-year overall survival, 3-year recurrence-free survival, and associated prognostic factors for survival among advanced-stage endometrial carcinoma patients at Siriraj Hospital. Methods: This study was conducted at the Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital, Mahidol University Bangkok, Thailand. A total of 415 patients that were diagnosed with advanced-stage endometrial carcinoma during January 1998 to December 2014 were enrolled. Data retrieved from medical records included baseline characteristics, surgico-pathological reports, treatment protocol, follow-up data, treatment response, and recurrence status. Three-year survival and recurrence-free survival were estimated by Kaplan-Meier method. Various factors were analyzed for significant association with survival. Results: Four hundred of 415 cases were included in the final analysis. There were 282 (70.5%) and 118 (29.5%) patients that were diagnosed with stage III and IV disease, respectively. Two hundred and eighty-two patients had complete response after primary treatment, and 94 (33.3%) patients had disease recurrence. The median follow-up and survival times were 24.5 and 42.5 months, respectively. The 3-year survival rate was 50%, and the median recurrence-free interval was 12.25 months. Multivariate analysis revealed high-grade tumor histology, lymph node metastasis, Eastern Cooperative Oncology Group (ECOG) performance status, and menopausal status to be significant prognostic factors for overall survival. Conclusion: Median survival among patients with advanced-stage endometrial carcinoma after primary treatment was 3 years. The significant prognostic factors were high grade tumor histology, lymph node metastasis, ECOG performance status, and menopausal status.

CircTNFRSF21, a newly identified circular RNA promotes endometrial carcinoma pathogenesis through regulating miR-1227-MAPK13/ATF2 axis.

Background: Circular RNA is a type of non-coding RNA with great potential in regulating gene expression and associated with disease progression. However, the role of circular RNA in endometrial carcinoma (EC) remains largely unknown.Results: In this study, we found that circTNFRSF21 was highly expressed in EC cells and tumor tissues. In vitro and in vivo results showed that circTNFRSF21 was linked to increased EC cell growth and EC xenografts formation in nude mice. Mechanically, we showed that circTNFRSF21 acts as a sponge of miR-1227 in EC cells to rescue MAPK13/ATF2 signaling pathway activity.Conclusions: Our studies suggested that in the EC, circTNFRSF21 promotes EC formation through downregulating miR-1227 expression and activating MAPK13/ATF2 signaling pathway. These findings provide strong evidence that circTNFRSF21-miR-1227-MAPK13/ATF2 axis is a promising target for EC treatment.Methods: qRT-PCR was used to detect circTNFRSF21expression in EC patients and EC cell lines. Cell growth, cell colony formation, cell apoptosis, cell cycle progression, and in vivo tumor formation assays were used to evaluate the roles of circTNFRSF21 in EC. Western blot, luciferase assay, RNA pull-down, siRNA knockdown, and CRISPR gene knock out assays were applied to study the mechanisms through which circTNFRSF21 regulates EC formation.

The clinicopathological characteristics and survival outcomes of endometrial carcinoma coexisting with or arising in adenomyosis: A pilot study

Little is known about the epidemiological and clinicopathological characteristics of endometrial endometrioid carcinoma (EEC) coexisting with or arising in adenomyosis (EEC-A or EEC-AIA) due to their rarity. This study compared EEC-A and EEC-AIA with endometrial carcinoma without adenomyosis. Cases of endometrial cancer treated at the study center from June 1, 2010, to June 1, 2017, were reviewed. The epidemiological, clinicopathological characteristics and survival outcomes were compared among three groups of endometrioid subtypes: group A, stage IA endometrial carcinoma patients without coexisting adenomyosis; group B, patients with EEC-A; and group C, patients with EEC-AIA. Among the 2080 patients reviewed, groups A, B, and C included 1043, 230 and 28 patients, respectively. Patients in group A and group B had similar clinicopathological and survival outcomes. Patients in group C were significantly younger and had less gravidity and parity than patients in groups A and B. More tumors from group C were grade 1, and they had a smaller maximum diameter and less mismatch repair deficiency than those from groups A and B. After a median follow-up of 57.0 months, the 5-year disease-free survival (DFS) rates of groups A, B and C were 96%, 91% and 100% (p = 0.045), respectively; the 5-year overall survival (OS) rates were 98%, 93% and 100%, respectively (p = 0.001), in the Kaplan-Meier analysis. However, these difference disappeared in a subgroup of stage IA patients in univariate and multivariate analysis. Cox regression analysis in stage IA patients also revealed no significant differences in survival outcome across the three groups. In conclusion, EEC-AIA exhibited specific clinicopathological characteristics that were probably associated with favorable survival outcomes. The characteristics and survival outcomes of EEC-A were similar to those of EEC without adenomyosis in stage IA patients.

The pan-cancer landscape of netrin family reveals potential oncogenic biomarkers

Recent cancer studies have found that the netrin family of proteins plays vital roles in the development of some cancers. However, the functions of the many variants of these proteins in cancer remain incompletely understood. In this work, we used the most comprehensive database available, including more than 10000 samples across more than 30 tumor types, to analyze the six members of the netrin family. We performed comprehensive analysis of genetic change and expression of the netrin genes and analyzed epigenetic and pathway relationships, as well as the correlation of expression of these proteins with drug sensitivity. Although the mutation rate of the netrin family is low in pan-cancer, among the tumor patients with netrin mutations, the highest number are Uterine Corpus Endometrial Carcinoma patients, accounting for 13.6% of cases (54 of 397). Interestingly, the highest mutation rate of a netrin family member is 38% for NTNG1 (152 of 397). Netrin proteins may participate in the development of endocrine-related tumors and sex hormone-targeting organ tumors. Additionally, the participation of NTNG1 and NTNG2 in various cancers shows their potential for use as new tumor markers and therapeutic targets. This analysis provides a broad molecular perspective of this protein family and suggests some new directions for the treatment of cancer.

The LncRNA AL161431.1 targets miR-1252-5p and facilitates cellular proliferation and migration via MAPK signaling in endometrial carcinoma.

The aim of this study was to determine the expression profile and the underlying mechanism of the long intergenic non-protein coding RNA AL161431.1 in EC (endometrial carcinoma). In this study, the expression data for the lncRNA AL161431.1 in EC was downloaded from The Cancer Genome Atlas (TCGA) database and used to examine its expression profile. quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot analysis were used to detect gene and protein expression, respectively. A subcellular fractionation assay was used to determine the location of AL161431.1. Cell Counting Kit-8 (CCK-8) and colony formation assays were used to evaluate cellular proliferation. Cell migration and wound healing assays were used to detect the effects on cell migration. RNA pull-down and Luciferase reporter assays were used to confirm the interaction between AL161431.1 and miR-1252-5p. High expression levels of AL161431.1 were observed in EC patients, tissues, and cells. Loss-of-function experiments validated the carcinogenic role of AL161431.1. Based on the determined cytoplasmic location of AL161431.1, we investigated the ceRNA network and its relation to AL161431.1, miR-1252-5p, and MAPK (mitogen-activated protein kinase) signaling in EC. The molecular mechanism of the interaction between AL161431.1 and miR-1252-5p, and its effects on the MAPK signaling pathway was validated using rescue experiments in Ishikawa cells. Our novel results indicate that AL161431.1 targets and binds to miR-1252-5p, resulting in the de-repression of MAPK signaling in EC cells. This highlights the potential for AL161431.1 to be targeted as a potent therapeutic strategy in the treatment of EC.

Co-existence of leiomyomas, adenomyosis and endometriosis in women with endometrial cancer

Leiomyomas, adenomyosis, and endometriosis are reported to be risk factors for endometrial carcinoma (EC), and adenomyosis and endometriosis also for ovarian carcinoma (OC). We aimed to describe the prevalence of these conditions in EC patients with or without an OC diagnosis, and to investigate their relationship with EC risk and prognostic factors in these patients. We evaluated the co-existence of these three conditions in 1399 EC patients, and compared the prevalence of epidemiological risk factors and tumor prognostic features in patients with each condition versus not. Prevalence of conditions was also assessed in the subset of patients with prior/concurrent OC. The observed coexistence of leiomyomas, adenomyosis and endometriosis significantly deviated from that expected (P = 1.2 × 10−8). Patients were more likely to: report a younger age at menarche (PTrend = 0.004) if they had leiomyomas; have used oral contraceptives (P = 6.6 × 10−5) or had ≥2 full-term pregnancies (PTrend = 2.0 × 10−9) if they had adenomyosis; be diagnosed with EC at younger age (P = 5.0 × 10−11) if they had endometriosis. Patients with prior/concurrent OC were more likely to be diagnosed at younger age (P = 5.0 × 10−5), have endometriosis (P = 9.9 × 10−7), and present with higher stage EC (PTrend = 6.6 × 10−5). These findings justify further consideration of these gynecologic conditions as independent risk and prognostic factors for EC.

Effectiveness of Pap Smears as Predictor in the Diagnosis of Carcinoma Endometrium at a Tertiary Oncology Centre in India

Endometrial carcinoma is the commonest malignancy of female genital tract in the developed world. No widely accepted screening test exists for endometrial cancer. However, cervical cytology may be useful in predicting endometrial disease. The aim of this study was to review the Pap smears of endometrial carcinoma patients for normal/ abnormal cytology and then correlate with clinico-pathological parameters. This was a retrospective study from January 2008 to December 2013. A total of 226 patients underwent surgery for endometrial cancer at this centre in this duration. Of these, medical records were available in 204 cases. Pap smear reports within previous 6 months of surgery were available in 180 cases. The relevant data of these patients were statistically analysed using standard statistical tests. A p value of ≤ 0.05 was considered significant. The patients were in the age group of 32 to 85 years. A total of 38 (21.1%) cases showed abnormal cytology on Pap test. The cervical cytology of carcinoma endometrium patients was then correlated and statistically analysed with various parameters like age, stage, grade of the disease, histology type and depth of myometrial invasion. The association was significant for higher histologic grade, advanced stage, deeper myometrial invasion and non-endometrioid histology. In our study, the rate of detection of abnormal cervical cytology in carcinoma endometrium is less in early stages but high in advanced stages and in the presence of poor prognostic factors, like higher histologic grade, deeper myometrial invasion and non-endometrioid histology.