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Endometrial (Uterus) Cancer

Endometrial cancer is a malignancy of the endometrium (the inner lining of the uterus, or womb) and is the most common gynaecological cancer, and accounts for 13% of all cancers in women. It is most frequently in women over age 50. A know risk factor is prior oestrogen-replacement therapy (however, oestrogen replacement also lowers risk of heart disease). Symptoms can include pelvic pain, and blood-soaked discharge - though these are also common symptoms related to menopausal changes.

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  • PubMed search for publications about Endometrial Cancer - Limit search to: [Reviews]

    PubMed Central search for free-access publications about Endometrial Cancer
    MeSH term: Endometrial Neoplasms
    International US National Library of Medicine
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Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Tsubamoto H, Inoue K, Sakata K, et al.
Itraconazole Inhibits AKT/mTOR Signaling and Proliferation in Endometrial Cancer Cells.
Anticancer Res. 2017; 37(2):515-519 [PubMed] Related Publications
BACKGROUND: Itraconazole is a common antifungal agent that has demonstrated anticancer activity in preclinical and clinical studies. This study investigated whether itraconazole exerts this effect in endometrial cancer (EC) cells.
MATERIALS AND METHODS: Cell viability was evaluated with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and gene and protein expression were assessed by microarray analysis and immunoblotting, respectively, in five EC cell lines.
RESULTS: Itraconazole-suppressed proliferation of AN3-CA, HEC-1A and Ishikawa cells (p<0.05) but not of HEC-50B or SNG-II cells. Itraconazole did not suppress GLI1 or GLI2 transcription but did inhibit the expression of mammalian target of rapamycin (mTOR) signaling components in AN3-CA and HEC-1A cells, while inducing that of microtubule-associated protein 1A/1B-light chain 3-II, a marker of autophagy. ATP-binding cassette transporter A1 gene was down-regulated in Ishikawa, HEC-50B and SNG-II cells.
CONCLUSION: Itraconazole treatment suppresses the growth of EC cells by inhibiting AKT/mTOR signalling.

Makris GM, Pouliakis A, Siristatidis C, et al.
Image analysis and multi-layer perceptron artificial neural networks for the discrimination between benign and malignant endometrial lesions.
Diagn Cytopathol. 2017; 45(3):202-211 [PubMed] Related Publications
BACKGROUND: This study aims to investigate the efficacy of an Artificial Neural Network based on Multi-Layer Perceptron (ANN-MPL) to discriminate between benign and malignant endometrial nuclei and lesions in cytological specimens.
METHODS: We collected 416 histologically confirmed liquid-based cytological smears from 168 healthy patients, 152 patients with malignancy, 52 with hyperplasia without atypia, 20 with hyperplasia with atypia, and 24 patients with endometrial polyps. The morphometric characteristics of 90 nuclei per case were analyzed using a custom image analysis system; half of them were used to train the MPL-ANN model, which classified each nucleus as benign or malignant. Data from the remaining 50% of cases were used to evaluate the performance and stability of the ANN. The MLP-ANN for the nuclei classification (numeric and percentage classifiers) and the algorithms for the determination of the optimum threshold values were estimated with in-house developed software for the MATLAB v2011b programming environment; the diagnostic accuracy measures were also calculated.
RESULTS: The accuracy of the MPL-ANN model for the classification of endometrial nuclei was 81.33%, while specificity was 88.84% and sensitivity 69.38%. For the case classification based on numeric classifier the overall accuracy was 90.87%, the specificity 93.03% and the sensitivity 87.79%; the indices for the percentage classifier were 95.91%, 93.44%, and 99.42%, respectively.
CONCLUSION: Computerized systems based on ANNs can aid the cytological classification of endometrial nuclei and lesions with sufficient sensitivity and specificity. Diagn. Cytopathol. 2017;45:202-211. © 2016 Wiley Periodicals, Inc.

Zeng N, Salker MS, Zhang S, et al.
1α,25(OH)2D3 Induces Actin Depolymerization in Endometrial Carcinoma Cells by Targeting RAC1 and PAK1.
Cell Physiol Biochem. 2016; 40(6):1455-1464 [PubMed] Related Publications
BACKGROUND: Cell proliferation and motility require actin reorganization, which is under control of various signalling pathways including ras-related C3 botulinum toxin substrate 1 (RAC1), p21 protein-activated kinase 1 (PAK1) and actin related protein 2 (ARP2). Tumour cell proliferation is modified by 1α,25-Dihydroxy-Vitamin D3 (1α,25(OH)2D3), a steroid hormone predominantly known for its role in calcium and phosphorus metabolism. The present study explored whether 1α,25(OH)2D3 modifies actin cytoskeleton in Ishikawa cells, a well differentiated endometrial carcinoma cell line.
METHODS: To this end, actin cytoskeleton was visualized by confocal microscopy. Globular over filamentous actin ratio was determined utilizing Western blotting and flow cytometry, transcript levels by qRT-PCR and protein abundance by immunoblotting.
RESULTS: A 24 hour treatment with 1α,25(OH)2D3 (100 nM) significantly decreased RAC1 and PAK1 transcript levels and activity, decreased ARP2 protein levels and depolymerized actin. The effect of 1α,25(OH)2D3 on actin polymerization was mimicked by pharmacological inhibition of RAC1 and PAK1.
CONCLUSIONS: 1α,25(OH)2D3 leads to disruption of RAC1 and PAK1 activity with subsequent actin depolymerization of endometrial carcinoma cells.

Kassem L, Abdel-Rahman O
Targeting mTOR pathway in gynecological malignancies: Biological rationale and systematic review of published data.
Crit Rev Oncol Hematol. 2016; 108:1-12 [PubMed] Related Publications
BACKGROUND: mTOR inhibitors are widely used in different malignancies with several trials testing their efficacy and safety in gynecological malignancies. We aimed to review the current evidence that support the expansion of using such drugs in the treatment of advanced gynecological cancers.
METHODS: A comprehensive systematic review of literature has been conducted to include prospective trials that used everolimus, temsirolimus or ridaforolimus in the management of gynecological cancers and have available efficacy and toxicity results.
RESULTS: A total of 23 studies including 980 patients were considered eligible for our review. Our review included 16 phase II and 7 phase I studies with the majority of patients having uterine cancers. Regarding Endometrial cancer, the CBR ranged from 21% to 60% and median PFS from 2.8 months to 7.3 months. In Ovarian cancers, CBR ranged from 24% to 50% and median PFS from 3.2 months to 5.9 months. In the single phase II study in cervical cancer the CBR was 61% and median PFS was 3.5 months. The toxicity profile was consistent with what was observed previously in other malignancies with fatigue, mucositis, and hematological toxicities being the most common adverse events observed.
CONCLUSION: mTOR inhibitors seem to be a promising option in the second line management of advanced gynecological cancers with best safety and efficacy outcomes when given as a single agent or in combination with hormonal treatment. More research is needed for better patient selection.

Santala S, Talvensaari-Mattila A, Soini Y, et al.
Cyclins A, B, E and p27 in Endometrial Endometrioid Adenocarcinoma.
Anticancer Res. 2016; 36(12):6467-6473 [PubMed] Related Publications
BACKGROUND/AIM: We have previously shown that cyclin A, B and E hold prognostic significance in endometrial endometrioid adenocarcinoma. The aim of this study was to investigate the impact of cyclin-dependent kinase inhibitor p27 on cancer-specific survival and other clinicopathological variables, as well as further analyze the relationship between p27 and cyclins A, B and E and their combined relation to prognosis in the disease.
PATIENTS AND METHODS: The study comprised of 211 patients surgically treated for endometrial endometrioid adenocarcinoma at the Oulu University Hospital between 1992 and 2000. Tissue samples were immunohistochemically stained for cyclins A, B and E, as well as p27. Clinicopathological data were retrospectively retrieved from the patients' records.
RESULTS: In this study, universally low cyclin expression was found to be an independent, favorable prognostic factor in endometrial endometrioid adenocarcinoma. A strong correlation was found between cyclin A and cyclin B expression and weaker correlations between other cyclin and p27 pairs. Nuclear p27 expression correlated with stage and produced near-significant results in univariate survival analysis.
CONCLUSION: Combining the expression level of different cyclins may be useful in determining the prognosis in endometrial cancer. Unfortunately, it remains unclear whether high p27 expression is a poor or a favorable prognostic factor. Further large-scale studies are required to assess the effects of cyclins and p27 in endometrial cancer.

Jiang H, Hu H, Lin F, et al.
S100P is Overexpressed in Squamous Cell and Adenosquamous Carcinoma Subtypes of Endometrial Cancer and Promotes Cancer Cell Proliferation and Invasion.
Cancer Invest. 2016; 34(10):477-488 [PubMed] Related Publications
S100P is known to affect tumor development and metastasis of various cancers, but its role in endometrial cancer is unclear. We reported that S100P expression was dramatically elevated in both endometrial squamous cell carcinoma and adenosquamous carcinoma, but not in adenocarcinoma and normal endometrial samples. Moreover, we revealed an oncogenic role of S100P promoting cell proliferation, invasion, and migration while reducing apoptosis, possibly via its upregulation and/or activation of receptors of advanced glycation end products and consequently the oncogenic PI3K-AKT and MAPK pathways. Therefore, S100P might be a specific biomarker and a potential drug target for squamous cell and adenosquamous carcinoma subtypes of endometrial cancer.

Wang D, Wang D, Wang N, et al.
Long Non-Coding RNA BANCR Promotes Endometrial Cancer Cell Proliferation and Invasion by Regulating MMP2 and MMP1 via ERK/MAPK Signaling Pathway.
Cell Physiol Biochem. 2016; 40(3-4):644-656 [PubMed] Related Publications
BACKGROUND/AIMS: Microarray screening had found BRAF-activated non-coding RNA (BANCR) was significantly upregulated in type 1 endometrial cancer (EC). This study aimed to assess the potential role of long non-coding RNA (lncRNA) BANCR in the pathogenesis and progression of type 1 EC.
METHODS: Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to confirm the expression of BANCR in type 1 EC tissue, and analyze its clinical significance. In vitro, RNA interference (siRNA) was used to investigate the biological role of BANCR in type 1 EC.
RESULTS: qRT-PCR revealed that the expression of lncRNA BANCR was higher in type 1 EC (P<0.01). BANCR expression was significantly correlated with FIGO stage, pathological grade, myometrial invasion, and lymph node metastasis. The expression of BANCR was significantly correlated with that of MMP2/MMP1. In vitro, knockdown of BANCR significantly suppressed proliferation, migration, and invasion of Ishikawa and HEC-1A cells, and significantly inhibited the ERK/MAPK signaling pathway that decreased MMP2 and MMP1 expression.
CONCLUSION: BANCR is highly expressed in type 1 EC tissue and promotes EC-cell proliferation, migration, and invasion by activating ERK/MAPK signaling pathway that regulates MMP2/MMP1 expression. BANCR is expected to become a prognostic marker and therapeutic target in type 1 EC.

Frost JA, Webster KE, Morrison J
Lymphadenectomy for Treatment of Early-Stage Endometrial Cancer.
JAMA Oncol. 2017; 3(1):117-118 [PubMed] Related Publications
Clinical Question: What is the association between lymphadenectomy and survival, disease recurrence, and surgical morbidity in women with presumed early-stage, low-grade endometrial carcinoma?
Bottom Line: The evidence from randomized clinical trials suggests that lymphadenectomy does not improve survival or decrease disease recurrence in women with early-stage, low-grade endometrial carcinoma. Furthermore lymphadenectomy is associated with an increase in both short- and long-term surgery-related systemic morbidity.

Sperling CD, Verdoodt F, Friis S, et al.
Statin use and risk of endometrial cancer: a nationwide registry-based case-control study.
Acta Obstet Gynecol Scand. 2017; 96(2):144-149 [PubMed] Related Publications
INTRODUCTION: Laboratory and epidemiological evidence have suggested that statin use may protect against the development of certain cancers, including endometrial cancer. In a nationwide registry-based case-control study, we examined the association between statin use and risk of endometrial cancer.
MATERIAL AND METHODS: Cases were female residents of Denmark with a primary diagnosis of endometrial cancer during 2000-2009. For each case, we selected 15 female population controls matched on date of birth (±one month) using risk-set sampling. Ever use of statin was defined as two or more prescriptions on separate dates. Conditional logistic regressions were used to estimate age-matched (by design) and multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CI) for endometrial cancer associated with statin use. The multivariable-adjusted models included parity, hormone replacement therapy (HRT), obesity, diabetes, chronic obstructive pulmonary disease and education. We evaluated whether the association between statin use and endometrial cancer varied with duration and intensity of statin use, type of endometrial cancer or patient characteristics.
RESULTS: The study population comprised 5382 endometrial cancer cases and 72 127 population controls. We observed no association between ever use of statins and endometrial cancer risk (OR 1.03, 95% CI 0.94-1.14). In addition, endometrial cancer risk did not vary substantially with duration or intensity of statin use. Stratification by type of endometrial cancer also yielded neutral ORs.
CONCLUSIONS: In our nationwide case-control study, we found no association between statin use and risk of endometrial cancer.

Hendrickson S, Bystrzonowski N, Kokkinos C, Butler P
Necrotising fasciitis caused by metastatic endometrial cancer: a rare cause of a life-threatening condition.
Ann R Coll Surg Engl. 2017; 99(2):e72-e74 [PubMed] Related Publications
We report a case of necrotising fasciitis caused by metastatic endometrial adenocarcinoma. Metastases to the lumbar spine with local invasion to the iliopsoas muscle led to an iliopsoas abscess, which subsequently progressed to necrotising fasciitis of the flank. This patient lacked common risk factors for necrotising fasciitis. There are no previous reports in the literature of necrotising fasciitis with this aetiology. We discuss the available evidence for aetiology of and risk factors for necrotising fasciitis, and the relation of time to surgery with prognosis.

Furuya M, Sato T, Tanaka R, et al.
Metachronous serous endometrial intraepithelial carcinoma and serous peritoneal carcinoma: analysis of probable independent lesions.
Diagn Pathol. 2016; 11(1):130 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Uterine serous endometrial intraepithelial carcinoma (SEIC) is an immediate precursor of invasive carcinoma. The majority of stage IA SEICs are curable, but those with latent peritoneal metastasis and/or capillary lymphatics invasion may have poor prognoses Careful pathologic staging is thus needed to predict the risk of recurrence and to determine postoperative therapeutic strategies.
CASE PRESENTATION: A 71-year-old woman was hospitalized for the treatment of peritoneal carcinoma. She had undergone total hysterectomy and bilateral salpingo-oophorectomy due to SEIC (stage IA) at age 63 years, and had received medical check-ups every year since. Elevated serum CA125 (184 U/mL) was detected for the first time 8 years after surgery. A thorough workup revealed no potential primary lesion other than that in the peritoneum. Tumor reduction surgery was performed. Histologic analysis of the peritoneal lesion was high-grade serous carcinoma. The peritoneal carcinoma was diffusely immunostained for p53; thus, possible recurrence of SEIC was suspected. Tumor DNAs were microdissected from the uterine and peritoneal lesions and p53 mutation analysis was done. SEIC and peritoneal carcinomas had distinct p53 mutations that were mutually exclusive.
CONCLUSIONS: The present case raised a concern about the difficulty of histologic staging for SEICs. Although SEICs confined to the uterine endometrium in most cases predict a good prognosis, microscopic metastasis to the peritoneum may not be detectable at hysterectomy. If secondary malignancies of a serous phenotype develop years later, comprehensive reexamination of SEIC is mandated, with the help of DNA analysis.

Papadia A, Gasparri ML, Siegenthaler F, et al.
FIGO stage IIIC endometrial cancer identification among patients with complex atypical hyperplasia, grade 1 and 2 endometrioid endometrial cancer: laparoscopic indocyanine green sentinel lymph node mapping versus frozen section of the uterus, why get around the problem?
J Cancer Res Clin Oncol. 2017; 143(3):491-497 [PubMed] Related Publications
PURPOSE: To compare two surgical strategies used to identify lymph node metastases in patients with preoperative diagnosis of complex atypical hyperplasia (CAH), grade 1 and 2 endometrial cancer (EC).
METHODS: Data on patients with preoperative diagnosis of CAH, grade 1 and 2 EC undergoing laparoscopic indocyanine green (ICG) sentinel lymph node (SLN) mapping followed by frozen section of the uterus were collected. When risk factors were identified at frozen section, patients were subjected to a systematic lymphadenectomy. False negative (FN) rates, negative predictive values (NPV), positive predictive values (PPV) and correlation with stage IIIC EC were calculated for the systematic lymphadenectomy based on frozen section of the uterus and for the SLN mapping.
RESULTS: Six (9.5%) out of 63 patients had lymph nodal metastases. Based on frozen section of the uterus, 22 (34.9%) and 15 (22.2%) patients underwent a pelvic and a pelvic and paraaortic lymphadenectomy, respectively. Five patients with stage IIIC disease were identified with a FN rate of 16.7% and a NPV and PPV of 97.6 and 27.3%, respectively. Overall and bilateral detection rates of ICG SLN mapping were 100 and 97.6%, respectively; no FN were recorded. The identification of patients with stage IIIC disease with ICG SLN mapping showed a NPV and PPV of 100%. Correlation between indication to lymphadenectomy and stage IIIC disease was poor (κ = 0.244) when based on frozen section of the uterus and excellent (κ = 1) when based on SLN mapping.
CONCLUSIONS: ICG SLN mapping reduces the number of unnecessary systematic lymphadenectomies and the risk of underdiagnosing patients with metastatic lymph nodes.

Bakir B, Sanli S, Bakir VL, et al.
Role of diffusion weighted MRI in the differential diagnosis of endometrial cancer, polyp, hyperplasia, and physiological thickening.
Clin Imaging. 2017 Jan - Feb; 41:86-94 [PubMed] Related Publications
Our purpose was to evaluate the role of diffusion-weighted imaging (DWI) in the diagnosis of various common pathologies of the uterine cavity, by comparing them with contrast-enhanced MRI findings. One hundred sixty-four patients with lesions in endometrial cavity were included in the study. The patients were grouped in four (one malignant and three benign groups). We have observed that the differences of the apparent diffusion coefficient, b1000q, and Cq values between various common benign and malignant lesions were statistically significant (P<.001). However, the differences of the values between benign groups were not statistically significant (P>.05). Alternatively, endometrial polyp group's signal intensity on DWI was different than the other groups.

Ciortea R, Berceanu C, Măluţan AM, et al.
Intraperitoneal Fat through GRP78: A Risk Factor for Endometrial Cancer.
Anal Cell Pathol (Amst). 2016; 2016:3496538 [PubMed] Free Access to Full Article Related Publications
Introduction. The identification of biological markers that indicate an increased risk for the development or recurrence of endometrial cancer (EC) in obese women might be useful for decreasing EC mortality and morbidity. Glucose-regulated protein 78 (GRP78) is a major protein of the endoplasmic reticulum expressed in all normal cells. Overexpression of GRP78 has been reported to be a tumoral biomarker. Increased detection of GRP78 is positively correlated with the tumoral stage and prognosis. This study aimed to identify a correlation between intraperitoneal fat, plasma GRP78 levels, and EC. Materials and Methods. Two groups of patients were included in the study: group I, 44 patients diagnosed with EC, and group II, 44 patients without gynecological pathology or inflammatory disorders. Visceral fat was determined by ultrasound and plasma GRP78 levels were measured. Results. Plasma GRP78 levels were significantly higher in patients with EC compared to the control group. Intraperitoneal fat was in a positive linear correlation with the plasma GRP78 level (p < 0.0001). Conclusion. The measurement of the GRP78 level associated with the determination of intraperitoneal fat can be a useful predictor for EC.

Elisei F, Crivellaro C, Giuliani D, et al.
Sentinel-node mapping in endometrial cancer patients: comparing SPECT/CT, gamma-probe and dye.
Ann Nucl Med. 2017; 31(1):93-99 [PubMed] Related Publications
OBJECTIVE: The aim of this study was to compare preoperative SPECT/CT with gamma-probe and methylene blue-dye (MBD) in the identification of sentinel lymph node (SLN) in early stage endometrial cancer.
METHODS: 40 stage-I EC patients (66.7 ± 9.7 years) underwent preoperative lymphoscintigraphy. After about 3 h from Tc-99m-albumin nanocolloid cervical injection, all patients underwent SPECT/CT study. MBD was injected into the cervix just before surgery under general anesthesia. All patients underwent SLN biopsy, hysterectomy, bilateral salpingo-oophorectomy, and radical regional lymphadenectomy. SPECT/CT findings were compared to those of gamma-probe and MBD techniques.
RESULTS: In 2 patients no nodal migration was observed, neither with MBD nor radiotracer. Detection rate of at least one SLN was 90% (36/40 patients) with SPECT/CT, 88% (35/40) intra-operatively with gamma-probe and 80% (32/40) with MBD. Only in 7/40 patients a bilateral migration was obtained with all considered modalities. In particular, bilateral detection was achieved in 26 patients with SPECT/CT, in 24 with gamma-probe and in 10 patients with MBD. The concordance site between SPECT/CT and intraoperative gamma-probe was 73% (29/40 patients: 2 without migration, 21 bilateral and 6 monolateral SLNs); while concordance site with MBD was found in 40% (16/40: 8 bilateral, 6 monolateral SLNs, 2 without SLNs). Overall, 628 LNs were dissected (mean 18 LNs per patient). The median number of SLNs removed was 2 (mean 2.5 per patient). Out of 91 SLNs: 43 were "hot and blue (HB)", 10 were blue only and 38 were hot only. LN metastases rate was 16%: 9/90 SLNs (7 HB, 2 hot only) were positive for metastases in 6 patients. Four non-SLNs were found positive in 3 patients, and all presented concomitant positive SLNs. False negative rate was 0%.
CONCLUSIONS: SPECT/CT had the highest detection rate and achieved the highest rate of bilateral mapping, compared to gamma-probe and MDB. SPECT/CT had moderate concordance with gamma-probe, and it can help the intraoperative detection of SLNs providing important information about their anatomic location.

Papadia A, Zapardiel I, Bussi B, et al.
Sentinel lymph node mapping in patients with stage I endometrial carcinoma: a focus on bilateral mapping identification by comparing radiotracer Tc99(m) with blue dye versus indocyanine green fluorescent dye.
J Cancer Res Clin Oncol. 2017; 143(3):475-480 [PubMed] Related Publications
PURPOSE: The aim of this study was to compare technetium radiocolloid (Tc99(m)) + blue dye (BD) versus Indocyanine green (ICG) fluorescent dye in terms of the overall detection rate and bilateral sentinel lymph node (SLN) mapping in patients with endometrial carcinoma.
METHODS: Patients from five European centers with apparently confined clinical stage I endometrial cancer were reviewed. A comparison was made between women who received SLN mapping with pelvic and/or aortic lymphadenectomy (LND), and women who underwent SLN algorithm (SA), was also performed between the two groups.
RESULTS: Three hundred and forty-two (342) women were involved (147 in the Tc99(m) + BD group and 195 in the ICG group). The overall detection rate of SLN biopsy was 97.3% (143/147) for women in the Tc99(m) + BD group and 96.9% (189/195) for women in the ICG group (p = 0.547). The bilateral mapping rate for ICG was 84.1%-significantly higher with respect to the 73.5% obtained with Tc99(m) + BD (p = 0.007). No differences in overall sensitivity (OS) and overall false negative rate (FNR) were seen between LND and SA (p value = 0.311), whereas the negative predictive value (NPV) was in favor of SA group (p value = 0.030).
CONCLUSIONS: In this study, fluorescent mapping using ICG resulted equivalent to the standard combined radiocolloid and BD, but real-time SLN mapping achieves a higher bilateral detection rate. The added value that this fast emerging technology promises to give certainly warrants future studies to further consolidate the advantages there are over the standard technique.

Du J, Li Y, Lv S, et al.
Endometrial sampling devices for early diagnosis of endometrial lesions.
J Cancer Res Clin Oncol. 2016; 142(12):2515-2522 [PubMed] Free Access to Full Article Related Publications
PURPOSE: Endometrial carcinoma is the most common gynecologic malignancy in both developed and some developing countries. Unlike cervical cancer, for which there is routine screening, only patients symptomatic for endometrial carcinoma typically seek medical help for its diagnosis and treatment. Dilatation and curettage (D&C) has been the standard procedure for evaluating suspicious endometrial lesions. The discomfort and injury caused by the D&C procedure, however, restrict its use as a screening method for early diagnosis of endometrial lesions. High-risk endometrial cancer patients would benefit from an effective and low-cost screening test. In recent years, several endometrial devices have been developed and proposed as screening tools.
METHODS: We have reviewed and evaluated the literature relating to the endometrial sampling devices in clinical use or clinical trials, with the goal of comparing devices and identifying the most appropriate ones for screening for endometrial lesions. Eligible literature was identified from systematic PubMed searches, and the relevant data were extracted. Comments, letters, unpublished data, conference proceedings, and case reports were excluded from our search. Seventy-four articles on endometrial sampling devices were obtained for this review.
RESULTS: The main screening devices for endometrial carcinoma are aspiration devices (such as the Vabra aspirator), Pipelle, Tao Brush, and SAP-1 device. Among these devices, the Tao Brush is the most promising endometrial sampler for screening for endometrial lesions. However, its sampling insufficiency, cost, and unsuccessful insertion rate (20 % in nulliparous and 8 % in parous women) are problematic.
CONCLUSIONS: A more accurate and low-cost endometrial sampler, with improved specimen sufficiency and higher sensitivity for endometrial lesions, needs tobe developed and clinically verified.

Koskas M, Depreeuw J, Moens S, et al.
Genomic Characterisation and Response to Trastuzumab and Paclitaxel in Advanced or Recurrent HER2-positive Endometrial Carcinoma.
Anticancer Res. 2016; 36(10):5381-5384 [PubMed] Related Publications
BACKGROUND/AIM: Human epidermal growth factor receptor 2 (HER2) positivity is associated with a worse prognosis in endometrial cancer (EC). Trastuzumab as a single agent did not demonstrate activity in such cases but there are no reports on its combined use with taxanes. We report the outcome in patients treated simultaneously with trastuzumab and paclitaxel for advanced or recurrent HER2-positive endometrial carcinoma and compared it to their microsatellite instability (MSI) status and PIK3CA mutational profiles.
PATIENTS AND METHODS: Patients with advancedor recurrent endometrial carcinoma showing HER2 overexpression (2+ or 3+ immunohistochemical staining) or HER2 amplification (fluorescence in situ hybridization (FISH) HER2/chromosome 17 centromere (CEP 17) ratio >2.0) were treated with trastuzumab (8 mg/kg) and paclitaxel (90 mg/m(2)) every three weeks. Evaluation of the response was assessed according to the response evaluation criteria in solid tumors (RECIST) guidelines. Endometrial tumors, sampled before the beginning of trastuzumab, were genotyped for PIK3CA hot spot mutations using Sequenom iPLEX Assay technology.
RESULTS: Two uterine serous adenocarcinomas and one grade 3 endometrioid adenocarcinoma showing HER2 positivity were treated with trastuzumab and paclitaxel. Between three and seven months of treatment, the three cases showed progressive disease. The genomic analysis of the three cases showed different mutational profiles. One case was found to have MSI and had one PIK3CA mutation. The two others showed no hot spot mutation for PIK3CA.
CONCLUSION: Even associated with paclitaxel, HER2-positive endometrial carcinomas poorly responded to trastuzumab. This report underlines the low accuracy of HER2 positivity to predict response of endometrial cancer to combined targeted therapy using trastuzumab and paclitaxel.

Hinshaw SJ, Gunderson S, Eastwood D, Bradley WH
Endometrial carcinoma: The perioperative and long-term outcomes of robotic surgery in the morbidly obese.
J Surg Oncol. 2016; 114(7):884-887 [PubMed] Related Publications
BACKGROUND AND METHODS: To evaluate surgical and pathologic outcomes of robotic assisted versus open hysterectomy for women with at least class II (BMI >35) and class III (BMI >40) obesity with endometrial cancer. Women with endometrial cancer and class II obesity, treated with open or robotic hysterectomy between 3/2005 and 3/2013 were eligible for inclusion in this retrospective cohort. Patients with class III obesity were reviewed both within the cohort of class II and as a separate subset. Data were collected on demographics, operative statistics, pathology, post-operative complications, and oncologic outcomes. Tests of significance used Chi-square, Fisher's exact test, t-test, and Wilcoxon rank-sum.
RESULTS: One hundred and thirty-six women with BMI >35 who underwent hysterectomy (56 robotic and 80 abdominal) were included. Patients undergoing robotic hysterectomies had fewer post-operative complications, shorter hospital stays, and lower blood loss compared to the abdominal group. A subset (83 of 136) with class III obesity had similar findings. Operative times, lymph node dissection rates, and lymph node yield (both pelvic and para-aortic) were similar between open and robotic surgery in both obesity classes. Oncologic outcomes and use of adjuvant treatment was not compromised.
CONCLUSIONS: Robotic hysterectomy is a safe and effective option for morbidly obese women with endometrial cancer. J. Surg. Oncol. 2016;114:884-887. © 2016 2016 Wiley Periodicals, Inc.

van der Putten LJ, van de Vijver K, Bartosch C, et al.
Reproducibility of measurement of myometrial invasion in endometrial carcinoma.
Virchows Arch. 2017; 470(1):63-68 [PubMed] Free Access to Full Article Related Publications
Myometrial invasion (MI) as a percentage (%MI), categorized into <50 or ≥50 %, is an important predictor of prognosis in endometrial carcinoma. Recent studies suggest that tumor-free distance (TFD) to serosa and the absolute depth of invasion (DOI) might be stronger predictors of prognosis. Although reproducibility is important in clinical practice for patient prognostication and treatment, reproducibility of these methods for the measurement of MI is largely unknown. One or two slides from 50 patients with FIGO stage I endometrioid endometrial carcinoma were viewed by seven gynecological pathologists, who were requested to measure %MI, TFD, and DOI. We categorized %MI as <50 % (including no MI) or ≥50 %, TFD as ≤1.75 or >1.75 mm (including no MI), ≤7 or >7 mm (including no MI), and ≤10 or >10 mm (including no MI) and DOI as <4 mm (including no MI) or ≥4 mm. Light's kappa for multi-rater agreement was calculated. The %MI, TFD, and DOI could be measured in 88, 83, and 79 % of cases, respectively. Kappa was 0.75 for %MI, 0.77, 0.73, and 0.69 respectively for TFD with cutoffs of 1.75, 7, and 10 mm, and 0.59 for DOI. Pathologists reach substantial agreement when measuring %MI and TFD and moderate agreement when measuring DOI. The %MI can be measured in more cases than TFD and DOI. This supports the use of %MI in daily clinical practice, but future studies should compare %MI and TFD more extensively, including inter-observer variability.

Shao X, Wang K, Liu X, et al.
Screening and verifying endometrial carcinoma diagnostic biomarkers based on a urine metabolomic profiling study using UPLC-Q-TOF/MS.
Clin Chim Acta. 2016; 463:200-206 [PubMed] Related Publications
BACKGROUND: Endometrial carcinoma (EOC) is a gynecological disease with one of the highest worldwide incidences. Due to the lack of typical clinical symptoms and limited sensitive screening methods used to diagnose endometrial carcinoma, the disease is easily neglected before patients are aware of its presence. Therefore, EOC results in serious impacts on women's lives and health. We screened diagnostic biomarkers of EOC with a noninvasive method that compared healthy individuals and endometrial hyperplasia (EOH) patients.
METHODS: The morning urine of 25 healthy individuals, 25 patients with EOC and 10 patients with EOH were analyzed using an ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) platform. Metabolomics data were used to screen the different metabolites according to principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) analyses. Furthermore, the screened biomarkers of the newly diagnosed EOC and EOH candidates and healthy individuals were verified using the predictive model of the support vector machine (SVM) to obtain EOC diagnostic biomarkers.
RESULTS: An EOC diagnostic biomarker group was found according to the metabolomics method. Five diagnostic biomarkers, including porphobilinogen, acetylcysteine, N-acetylserine, urocanic acid and isobutyrylglycine, were significantly changed in the EOC patients. Among them, porphobilinogen and acetylcysteine were significantly down-regulated, while N-acetylserine, urocanic acid and isobutyrylglycine were significantly up-regulated.
CONCLUSIONS: Disturbances in these biomarkers have negative impacts on the body's metabolic functioning. The EOC diagnostic biomarker group can provide a clinical reference for diagnosing EOC and insight into the diagnosis of other diseases in the clinic.

Ke J, Yang Y, Che Q, et al.
Prostaglandin E2 (PGE2) promotes proliferation and invasion by enhancing SUMO-1 activity via EP4 receptor in endometrial cancer.
Tumour Biol. 2016; 37(9):12203-12211 [PubMed] Free Access to Full Article Related Publications
Prostaglandin E2 (PGE2), a derivative of arachidonic acid, has been identified as a tumorigenic factor in many cancers in recent studies. Prostaglandin E synthase 2 (PTGES2) is an enzyme that in humans is encoded by the PTGES2 gene located on chromosome 9, and it synthesizes PGE2 in human cells. In our study, we selected 119 samples from endometrial cancer patients, with 50 normal endometrium tissue samples as controls, in which we examined the expression of PTGES2. Both immunohistochemistry (IHC) and Western blot analyses demonstrated that synthase PTGES2, which is required for PGE2 synthesis, was highly expressed in endometrium cancer tissues compared with normal endometrium. Stable PTGES2-shRNA transfectants were generated in Ishikawa and Hec-1B endometrial cancer cell lines, and transfection efficiencies were confirmed by RT-PCR and Western blot analyses. We found that PGE2 promoted proliferation and invasion of cells in Ishikawa and Hec-1B cells by cell counting kit-8 tests (CCK8) and transwell assays, respectively. PGE2 stimulation enhanced the expression of SUMO-1, via PGE2 receptor subtype 4 (EP4). Further analysis implicated the Wnt/β-catenin signaling pathway function as the major mediator of EP4 and SUMO-1. The increase in SUMO-1 activity prompted the SUMOlyation of target proteins which may be involved in proliferation and invasion. These findings suggest SUMO-1 and EP4 as two potential targets for new therapeutic or prevention strategies for endometrial cancers.

Pusey M, Bail S, Xu Y, et al.
Inhibition of protein methylesterase 1 decreased cancerous phenotypes in endometrial adenocarcinoma cell lines and xenograft tumor models.
Tumour Biol. 2016; 37(9):11835-11842 [PubMed] Related Publications
Protein methylesterase 1 (PME-1) promotes cancerous phenotypes through the demethylation and inactivation of protein phosphatase 2A. We previously demonstrated that PME-1 overexpression promotes Akt, ERK, and may promote Wnt signaling and increases tumor burden in a xenograft model of endometrial cancer. Here, we show that covalent PME-1 inhibitors decrease cell proliferation and invasive growth in vitro but have no effect in vivo at the concentrations tested; however, depletion of PME-1 with shRNA in an endometrial cancer xenograft model significantly reduced tumor growth. Thus, discovery of more potent PME-1 inhibitors may be beneficial for the treatment of endometrial cancer.

Sahbai S, Taran FA, Fiz F, et al.
Pericervical Injection of 99mTc-Nanocolloid Is Superior to Peritumoral Injection for Sentinel Lymph Node Detection of Endometrial Cancer in SPECT/CT.
Clin Nucl Med. 2016; 41(12):927-932 [PubMed] Related Publications
PURPOSE: Scintigraphic mapping of sentinel lymph node (SLN) is increasingly performed in patients with endometrial carcinoma although its routine clinical use is still under investigation. The purpose of this study was to compare preoperative SLN detection by means of SPECT/CT using pericervical (PC) versus hysteroscopic peritumoral (PT) injection.
PATIENTS AND METHODS: One hundred forty consecutive patients with endometrial carcinoma who underwent surgery and preoperative SLN SPECT/CT with Tc-nanocolloid were included. Seventy women received hysteroscopic injection at 3 PT sites, and 70 women received PC injection at 3-, 6-, 9-, and 12-o'clock positions. Each patient underwent SPECT/CT followed by modified radical hysterectomy with lymphadenectomy on the day after. Histopathological results were collected for validation.
RESULTS: Three hundred thirty-four SLNs were detected by SPECT/CT in 106 patients (mean, 3.15; range, 1-9). The detection rate after PC nanocolloid injection was 83% versus 69% after PT injection (Pearson χ test, P = 0.049). However, PT application resulted in a higher rate of para-aortic SLNs (PC: 60% vs PT: 38% of positive scans, P = 0.02). SPECT/CT yielded an overall sensitivity of 70% for the SLN detection in women with lymph node metastases with 3 false-negative cases. Failure to detect SLN was mostly associated with uptake in the reticuloendothelial system (liver, spleen, and bone marrow) or peritoneal diffusion in both cohorts. Negative scans after PT application often showed a minor to even failing injection depot.
CONCLUSIONS: Pericervical injection leads to a significantly better detection rate of SLN on SPECT/CT while reducing invasiveness of the injection procedure. Failure to detect SLN seems to be associated with major venous drainage.

Švajdler M, Michal M, Dubinský P, et al.
Endometrial Endometrioid Carcinoma With Large Cystic Growth Configuration and Deceptive Pattern of Invasion Associated With Abundant Nodular Fasciitis-like Stroma: A Unique Hitherto Unreported Histology in Endometrioid Carcinoma.
Adv Anat Pathol. 2016; 23(6):381-384 [PubMed] Related Publications
We describe a case of an unusual endometrial endometrioid carcinoma occurring in a 67-year-old woman. The tumor involved uterine corpus as well as lower uterine segment and presented as polypoid tumor protruding through the cervical orifice. Microscopically, the tumor was characterized by broad zones of cytologically bland fibromyxoid stroma resembling nodular fasciitis, showing vaguely nodular architecture. Neoplastic glands were characterized by interconnected elongated slit-like and large cystic profiles, mostly lined by flattened epithelium with variable squamous differentiation, whereas typical columnar endometrioid cells were only focally present. Voluminous nodules of the stroma produced phyllodes-like appearance of the tumor. The tumor showed some resemblance to the microcystic, elongated, and fragmented (MELF) glands growth pattern, but in contrast with MELF pattern, where fibromyxoid change occurs focally, in the presented case abundant myofibroblastic proliferation was present throughout the tumor and the neoplastic glands showed anastomosing "large cystic" rather than "small cystic" profiles. Some of the neoplastic glands presented almost complete or complete squamous differentiation, with relatively bland-looking squamous cells and no hint of endometrioid differentiation, which resulted in initial misdiagnosis of Müllerian adenofibroma. We believe that nodular fasciitis-like pattern represents yet undescribed, and diagnostically challenging pattern of invasion in endometrial endometrioid carcinoma.

Kuramoto H, Iwami Y, Sugimoto N, et al.
Cytological Characteristics of Endometrial Phasing Using the Specimens Prepared with the Liquid-Based Procedure: Comparison with the Conventional Procedure.
Acta Cytol. 2016; 60(5):429-437 [PubMed] Related Publications
OBJECTIVE: To evaluate whether or not the liquid-based procedure (LBP) for endometrial cytology is as worthwhile for endometrial phasing as conventional slides.
MATERIALS AND METHODS: The subjects were 81 women who underwent endometrial cytology and were defined as negative. The specimens obtained by either Endocyte® or Masubuchi aspiration tube® were processed first with the conventional procedure and then with LBP using TACAS™.
RESULTS: (1) The number of subjects diagnosed by the conventional method as having proliferative, mid-, middle-secretory and late-secretory and atrophic phases was 40, 11, 10, 0 and 20, respectively. The rate of agreement with those using LBP was 87.7%. (2) Incidences of large clusters, ductal clusters, palisade arrangement, uneven staining and dirty mucous background detected were significantly higher with the conventional method, whereas with LBP clean background, inconspicuous bonding of cells, scattered solitary glandular cells, clear well-stained cytoplasm and cell compactness were higher. (3) Especially in the proliferative phase, clusters tended to be smaller and lose their architectural structures, and scattered solitary columnar cells were present. (4) Cells in the mid-phase tended to have loose contact and to mimic other phases.
CONCLUSIONS: Cytodiagnosis of endometrial phasing prepared with LBP is feasible to perform when some modifications are implemented.

Kommoss F, Kommoss F, Grevenkamp F, et al.
L1CAM: amending the "low-risk" category in endometrial carcinoma.
J Cancer Res Clin Oncol. 2017; 143(2):255-262 [PubMed] Related Publications
PURPOSE: Low- and intermediate-risk endometrial carcinomas have an excellent prognosis. Nonetheless, a small subgroup of such patients will experience unexpected relapse. Recently L1CAM was suggested to be a strong prognosticator in endometrial carcinoma. The focus of our study was on low- and intermediate-risk disease, where no or only limited adjuvant treatment is recommended according to current guidelines.
METHODS: Endometrial carcinomas of low, intermediate and high-intermediate risk according to published 2016 consensus guidelines were identified. The study was limited to cases with previous central pathology review focusing on histotype, depth of myometrial invasion, presence of lymphovascular space invasion (LVSI) and MELF pattern of invasion. Standard L1CAM immunohistochemistry was performed. Disease-specific uni- and multivariate survival analyses were calculated.
RESULTS: A total of 344 cases were available for immunohistochemistry (low-risk: n = 250; intermediate-risk: n = 67; high-intermediate-risk: n = 27). L1CAM positivity rates were: 29/344 (8.4 %; all cases), 18/250 (7.2 %; low-risk), 6/67 (9.0 %; intermediate-risk) and 5/27 (18.5 %; high-intermediate-risk). Expression of L1CAM was independent of LVSI and MELF. L1CAM was a significant independent prognosticator for disease-specific survival with a hazard ratio of 5.98 [CI 1.50-22.14, p = 0.012]. Adverse prognostic significance of L1CAM positivity was maintained after low-risk subgroup analysis (5-year disease-specific survival rates 71.8 vs. 100 %, p < 0.0001). All four tumour-related deaths in the subgroup of low-risk disease occurred in patients with L1CAM-positive tumours.
CONCLUSION: The current definition of "low-risk" in endometrial carcinoma should be amended. "Low-risk carcinomas" should be limited to L1CAM-negative tumours. L1CAM status will play a key role in future algorithms to tailor adjuvant treatment and patient follow-up strategies.

Li Z, Wei D, Yang C, et al.
Overexpression of long noncoding RNA, NEAT1 promotes cell proliferation, invasion and migration in endometrial endometrioid adenocarcinoma.
Biomed Pharmacother. 2016; 84:244-251 [PubMed] Related Publications
Long noncoding RNAs (lncRNAs) are emerging as important modulators in the biological processes and tumorigenesis. However, whether lncRNAs are involved in endometrial endometrioid adenocarcinoma (EEC) remains unclear. In the present study, we explored the expression pattern, clinical significance and biological function of nuclear enriched abundant transcript 1 (NEAT1) in EEC. The expression levels of NEAT1 were elevated in EEC tissues and cell lines, and higher expression levels of NEAT1 were positively correlated with FIGO stage and lymph node metastasis. Overexpression of NEAT1 in HEC-59 cells transfected with pGCMV-NEAT1 promotes cell growth, colony formation ability as well as invasive and migratory ability; while knock-down of NEAT1 in HEC-59 cells by siNEAT1 transfection exhibited the opposite effects. Flow cytometry analysis showed that overexpression of NEAT1 led to an increase in S-phase cells and attenuated cell apoptosis, and knock-down of NEAT1 induced G0/G1 arrest and also induced cell apoptosis in HEC-59 cells. Tumor metastasis real-time PRC array showed that six metastasis-related genes (c-myc, insulin like growth factor 1(IGF1), matrix metallopeptidase 2 (MMP-2) and matrix metallopeptidase 7(MMP-7) were up-regulated, and Cadherin 1 and TIMP metallopeptidase inhibitor 2 were down-regulated) in NEAT1-overexpressing HEC-59 cells. Further qRT-PCR and western blot results confirmed that c-myc, IFG1, MMP-2 and MMP-7 were dys-regulated by NEAT1. Together, our data underscore the significance of NEAT1 in EEC development, and NEAT1 may a potential therapeutic target for EEC.

Dumas L, Ring A, Butler J, et al.
Improving outcomes for older women with gynaecological malignancies.
Cancer Treat Rev. 2016; 50:99-108 [PubMed] Related Publications
The incidence of most gynaecological malignancies rises significantly with increasing age. With an ageing population, the proportion of women over the age of 65 with cancer is expected to rise substantially over the next decade. Unfortunately, survival outcomes are much poorer in older patients and evidence suggests that older women with gynaecological cancers are less likely to receive current standard of care treatment options. Despite this, older women are under-represented in practice changing clinical studies. The evidence for efficacy and tolerability is therefore extrapolated from a younger; often more fit population and applied to in every day clinical practice to older patients with co-morbidities. There has been significant progress in the development of geriatric assessment in oncology to predict treatment outcomes and tolerability however there is still no clear evidence that undertaking a geriatric assessment improves patient outcomes. Clinical trials focusing on treating older patients are urgently required. In this review, we discuss the evidence for treatment of gynaecological cancers as well as methods of assessing older patients for therapy. Potential biomarkers of ageing are also summarised.

Skręt-Magierło J, Raś R, Barnaś E, Skręt A
Evaluation of the hospital environment for women with endometrial cancer.
Ann Agric Environ Med. 2016; 23(3):511-6 [PubMed] Related Publications
INTRODUCTION AND OBJECTIVES: The aim of the study was describe the factors determining the evaluation of the hospital environment, especially satisfaction with care and individual needs of cancer patients.
MATERIAL AND METHODS: The study comprised 80 women with endometrial cancer diagnosed and treated surgery in the Clinic of Gynaecology and Obstetrics in Rzeszow, Poland, between 2011-2012. The study used 3 questionnaires: the Goals Attainment Scaling (GAS) questionnaires, and questionnaires developed by the EORTC Quality of Life group, i.e. the QLQ C-30 (general module) and the In- PATSAT-32.
RESULTS: Respondents indicated 36 goals/expectations and the most common (over 50%) concerned the normal course of the post-operative period. The overall index of all goals which were met was 7.0 points. General quality of life reported by respondents before surgery was at a medium level (52.3+16.8%). Emotional functioning received the lowest scores (61.0+18.8%). Most respondents assessed manual skills of hospital doctors and nurses as the best in the In-PATSAT 32 scale i.e. 69.9±14.7% and 67.3±16.1%, respectively. The worst ratings concerned access to hospital from the outside (50.8±16.9%) and easy orientation inside the buildings (55.9±16.0%).
CONCLUSIONS: Analysis of correlations between GAS and the In-PATSAT32 scales proved that they cannot be used interchangeably since they measure different aspects of a patient's satisfaction with hospital care. For this reason, the application of idiographic and nomothetic tests among cancer patients is helpful for evaluation of the hospital environment.

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