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10 pages, 500 KiB

Open AccessArticle

Expression Pattern of Leptin and Its Receptors in Endometrioid Endometrial Cancer

by Dariusz Boroń, Robert Nowakowski, Beniamin Oskar Grabarek, Nikola Zmarzły and Marcin Opławski

J. Clin. Med. 2021, 10(13), 2787; https://doi.org/10.3390/jcm10132787 - 24 Jun 2021

Cited by 16 | Viewed by 2039

Abstract

The identification of novel molecular markers and the development of cancer treatment strategies are very important as cancer incidence is still very high. Obesity can contribute to cancer progression, including endometrial cancer. Adipocytes secrete leptin, which, when at a high level, is associated [...] Read more.

The identification of novel molecular markers and the development of cancer treatment strategies are very important as cancer incidence is still very high. Obesity can contribute to cancer progression, including endometrial cancer. Adipocytes secrete leptin, which, when at a high level, is associated with an increased risk of cancer. The aim of this study was to determine the expression profile of leptin-related genes in the endometrial tissue samples and whole blood of patients. The study material included tissue samples and whole blood collected from 30 patients with endometrial cancer and 30 without cancer. Microarrays were used to assess the expression profile of leptin-related genes. Then, the expression of leptin (LEP), leptin receptor (LEPR), leptin receptor overlapping transcript (LEPROT), and leptin receptor overlapping transcript-like 1 (LEPROTL1) was determined by the Real-Time Quantitative Reverse Transcription Reaction (RT-qPCR). The serum leptin concentration was evaluated using Enzyme-linked immunosorbent assay (ELISA). Leptin and its receptors were overexpressed both at the mRNA and protein levels. Furthermore, there were strong positive correlations between leptin levels and patient Body Mass Index (BMI). Elevated levels of leptin and its receptors may potentially contribute to the progression of endometrial cancer. These observations may be useful in designing endometrial cancer treatment strategies. Full article

(This article belongs to the Special Issue Clinical Advances on Endometrial Cancer)

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14 pages, 1907 KiB

Open AccessArticle

The Clinical Significance of DJ1 and L1CAM Serum Level Monitoring in Patients with Endometrial Cancer

by Marketa Bednarikova, Petra Vinklerova, Jana Gottwaldova, Petra Ovesna, Jitka Hausnerova, Lubos Minar, Michal Felsinger, Dalibor Valik, Zdenka Cermakova and Vit Weinberger

J. Clin. Med. 2021, 10(12), 2640; https://doi.org/10.3390/jcm10122640 - 15 Jun 2021

Cited by 7 | Viewed by 1996

Abstract

Circulating tumor markers are not routinely used in patients with endometrial cancer (EC). This pilot study evaluated the role of monitoring new biomarkers DJ1 and L1CAM, in correlation with CA125 and HE4, for the effects of anticancer treatment and preoperative management in EC [...] Read more.

Circulating tumor markers are not routinely used in patients with endometrial cancer (EC). This pilot study evaluated the role of monitoring new biomarkers DJ1 and L1CAM, in correlation with CA125 and HE4, for the effects of anticancer treatment and preoperative management in EC patients. Serial serum levels of DJ1, L1CAM, CA125 and HE4 were collected in 65 enrolled patients. Serum DJ1, L1CAM, CA125 and HE4 levels were significantly higher at the time of diagnosis compared to those measured during follow-up (FU). In patients with recurrent disease, serum DJ1, CA125 and HE4 levels were significantly higher at the time of recurrence compared to levels in disease-free patients. Serum L1CAM levels were also higher in patients with recurrence but without reaching statistical significance. While DJ1 levels were not affected by any of the observed patient-related characteristics, L1CAM levels were significantly higher in patients with age ≥60 years who were overweight. At the time of EC diagnosis, DJ1 and L1CAM serum levels did not correlate with stage, histological type or risk of recurrence. This is a preliminary description of the potential of serial DJ1 and L1CAM serum level measurement for monitoring the effects of treatment in EC patients. Full article

(This article belongs to the Special Issue Clinical Advances on Endometrial Cancer)

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12 pages, 2596 KiB

Open AccessArticle

CD133 Expression in the Nucleus Is Associated with Endometrial Carcinoma Staging and Tumor Angioinvasion

by Milosz Pietrus, Kazimierz Pitynski, Marcin Waligora, Katarzyna Milian-Ciesielska, Monika Bialon, Artur Ludwin and Klaudia Skrzypek

J. Clin. Med. 2021, 10(10), 2144; https://doi.org/10.3390/jcm10102144 - 15 May 2021

Cited by 4 | Viewed by 2371

Abstract

Background: (1) Endometrial cancer is one of the most common cancers affecting women, with a growing incidence. To better understand the different behaviors associated with endometrial cancer, it is necessary to understand the changes that occur at a molecular level. CD133 is one [...] Read more.

Background: (1) Endometrial cancer is one of the most common cancers affecting women, with a growing incidence. To better understand the different behaviors associated with endometrial cancer, it is necessary to understand the changes that occur at a molecular level. CD133 is one of the factors that regulate tumor progression, which is primarily known as the transmembrane glycoprotein associated with tumor progression or cancer stem cells. The aim of our study was to assess the impact of subcellular CD133 expression on the clinical course of endometrial cancer. (2) Methods: CD133 expression in the plasma membrane, nucleus, and cytoplasm was assessed by immunohistochemical staining in a group of 64 patients with endometrial cancer representing FIGO I-IV stages, grades 1–3 and accounting for tumor angioinvasion. (3) Results: Nuclear localization of CD133 expression was increased in FIGO IB-IV stages compared to FIGO IA. Furthermore, CD133 expression in the nucleus and plasma membrane is positively and negatively associated with a higher grade of endometrial cancer and angioinvasion, respectively. (4) Conclusions: Our findings suggest that positive nuclear CD133 expression in the tumor may be related to a less favorable prognosis of endometrial carcinoma patients and has emerged as a useful biomarker of a high-risk group. Full article

(This article belongs to the Special Issue Clinical Advances on Endometrial Cancer)

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11 pages, 3284 KiB

Open AccessArticle

Tie-2, G-CSF, and Leptin as Promising Diagnostic Biomarkers for Endometrial Cancer: A Pilot Study

by Luka Roškar, Teja Klančič, Tamara Knific, Tea Lanišnik Rižner and Špela Smrkolj

J. Clin. Med. 2021, 10(4), 765; https://doi.org/10.3390/jcm10040765 - 15 Feb 2021

Cited by 6 | Viewed by 3393

Abstract

Preoperative determination of the extent of endometrial cancer (EC) would avoid the complications associated with radical surgery. Screening of patients’ plasma biomarkers might enable a more precise diagnosis of EC and a tailored treatment approach. This prospective case-control monocentric pilot study included 76 [...] Read more.

Preoperative determination of the extent of endometrial cancer (EC) would avoid the complications associated with radical surgery. Screening of patients’ plasma biomarkers might enable a more precise diagnosis of EC and a tailored treatment approach. This prospective case-control monocentric pilot study included 76 postmenopausal women (38 endometrioid EC patients and 38 control patients with benign gynecological conditions), and 37 angiogenic factors (AFs) were investigated as potential biomarkers for EC. AF concentrations in preoperative plasma samples were measured using Luminex xMAP™ multiplexing technology. The plasma levels of sTie-2 and G-CSF were significantly lower in EC compared to control patients, whereas the plasma levels of leptin were significantly higher in EC patients. Neuropilin-1 plasma levels were significantly higher in patients with type 2 EC (grade 3) compared to patients with lower grade cancer or controls. Follistatin levels were significantly higher in patients with lymphovascular invasion, and IL-8 plasma levels were significantly higher in patients with metastases. If validated, the plasma concentrations of the indicated AFs could represent an important additional diagnostic tool for the early detection and characterization of EC. This could guide the decision-making on the extent of surgery. Further studies with larger patient numbers are currently ongoing. Full article

(This article belongs to the Special Issue Clinical Advances on Endometrial Cancer)

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11 pages, 1042 KiB

Open AccessArticle

An MRI-Based Radiomic Prognostic Index Predicts Poor Outcome and Specific Genetic Alterations in Endometrial Cancer

by Havjin Jacob, Julie A. Dybvik, Sigmund Ytre-Hauge, Kristine E. Fasmer, Erling A. Hoivik, Jone Trovik, Camilla Krakstad and Ingfrid S. Haldorsen

J. Clin. Med. 2021, 10(3), 538; https://doi.org/10.3390/jcm10030538 - 02 Feb 2021

Cited by 14 | Viewed by 2919

Abstract

Integrative tumor characterization linking radiomic profiles to corresponding gene expression profiles has the potential to identify specific genetic alterations based on non-invasive radiomic profiling in cancer. The aim of this study was to develop and validate a radiomic prognostic index (RPI) based on [...] Read more.

Integrative tumor characterization linking radiomic profiles to corresponding gene expression profiles has the potential to identify specific genetic alterations based on non-invasive radiomic profiling in cancer. The aim of this study was to develop and validate a radiomic prognostic index (RPI) based on preoperative magnetic resonance imaging (MRI) and assess possible associations between the RPI and gene expression profiles in endometrial cancer patients. Tumor texture features were extracted from preoperative 2D MRI in 177 endometrial cancer patients. The RPI was developed using least absolute shrinkage and selection operator (LASSO) Cox regression in a study cohort (n = 95) and validated in an MRI validation cohort (n = 82). Transcriptional alterations associated with the RPI were investigated in the study cohort. Potential prognostic markers were further explored for validation in an mRNA validation cohort (n = 161). The RPI included four tumor texture features, and a high RPI was significantly associated with poor disease-specific survival in both the study cohort (p < 0.001) and the MRI validation cohort (p = 0.030). The association between RPI and gene expression profiles revealed 46 significantly differentially expressed genes in patients with a high RPI versus a low RPI (p < 0.001). The most differentially expressed genes, COMP and DMBT1, were significantly associated with disease-specific survival in both the study cohort and the mRNA validation cohort. In conclusion, a high RPI score predicts poor outcome and is associated with specific gene expression profiles in endometrial cancer patients. The promising link between radiomic tumor profiles and molecular alterations may aid in developing refined prognostication and targeted treatment strategies in endometrial cancer. Full article

(This article belongs to the Special Issue Clinical Advances on Endometrial Cancer)

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11 pages, 1662 KiB

Open AccessArticle

Incidence of Atrial Fibrillation in Postmenopausal Women with Endometrial Cancer

by Mariana S. Parahuleva, Julian Kreutz, Gerhild Euler, Dora Terzieva, Amar Mardini, Ekaterina Uchikova and Nikoleta Parahuleva

J. Clin. Med. 2021, 10(2), 266; https://doi.org/10.3390/jcm10020266 - 13 Jan 2021

Cited by 3 | Viewed by 1791

Abstract

Endometrial cancer (EC) has been associated with an increased risk of cardiovascular disease, including atrial fibrillation (AF). We performed a prospective, case-controlled analysis among 310 Bulgarian women with new-onset, histologically confirmed EC, free of AF at the baseline survey, and women with normal [...] Read more.

Endometrial cancer (EC) has been associated with an increased risk of cardiovascular disease, including atrial fibrillation (AF). We performed a prospective, case-controlled analysis among 310 Bulgarian women with new-onset, histologically confirmed EC, free of AF at the baseline survey, and women with normal (senile) endometrium/endometrial hyperplasia as a control group (n = 205). The risk of AF as well as relationship of adiponectin (APN) and high sensitivity C-reactive protein (hs-CRP) levels with AF in women with EC were calculated by Cox proportional hazards models. During the mean follow-up of 2.5 ± 0.5 years, new-onset AF had occurred in 11.7% of women with EC vs. 5.8% in the control group (p < 0.01). The risk of AF was highest in the first 6 months after new-onset EC, with an incidence rate ratio (IRR) of 1.19 (95% CI 1.10–1.29; p = 0.01). Women with EC, who were obese (body mass index (BMI) > 30 kg/m²) and younger (age < 60) were found to be more likely to develop AF (HR 1.95; 95% CI 1.18–3.32; p = 0.05). APN levels were not significantly associated with new-onset AF (95% CI 0.87–1.21; p = 0.063). However, the secondary analysis showed evidence of APN–AF association when adjusted for BMI (2.05; 95% CI 1.04–4.04; p = 0.037). We conclude that EC was significantly associated with the incidence of AF. Full article

(This article belongs to the Special Issue Clinical Advances on Endometrial Cancer)

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15 pages, 3491 KiB

Open AccessArticle

AKR1C3 Is Associated with Better Survival of Patients with Endometrial Carcinomas

by Marko Hojnik, Nataša Kenda Šuster, Špela Smrkolj, Snježana Frković Grazio, Ivan Verdenik and Tea Lanišnik Rižner

J. Clin. Med. 2020, 9(12), 4105; https://doi.org/10.3390/jcm9124105 - 19 Dec 2020

Cited by 10 | Viewed by 2263

Abstract

The aldo-keto reductase (AKR) superfamily is gaining attention in cancer research. AKRs are involved in important biochemical processes and have crucial roles in carcinogenesis and chemoresistance. The enzyme AKR1C3 has many functions, which include production of prostaglandins, androgens and estrogens, and metabolism of [...] Read more.

The aldo-keto reductase (AKR) superfamily is gaining attention in cancer research. AKRs are involved in important biochemical processes and have crucial roles in carcinogenesis and chemoresistance. The enzyme AKR1C3 has many functions, which include production of prostaglandins, androgens and estrogens, and metabolism of different chemotherapeutics; AKR1C3 is thus implicated in the pathophysiology of different cancers. Endometrial and ovarian cancers represent the majority of gynecological malignancies in developed countries. Personalized treatments for these cancers depend on identification of prognostic and predictive biomarkers that allow stratification of patients. In this study, we evaluated the immunohistochemical (IHC) staining of AKR1C3 in 123 paraffin-embedded samples of endometrial cancer and 99 samples of ovarian cancer, and examined possible correlations between expression of AKR1C3 and other clinicopathological data. The IHC expression of AKR1C3 was higher in endometrial cancer compared to ovarian cancer. In endometrioid endometrial carcinoma, high AKR1C3 IHC expression correlated with better overall survival (hazard ratio, 0.19; 95% confidence interval, 0.06−0.65, p = 0.008) and with disease-free survival (hazard ratio, 0.328; 95% confidence interval, 0.12–0.88, p = 0.027). In patients with ovarian cancer, there was no correlation between AKR1C3 IHC expression and overall and disease-free survival or response to chemotherapy. These results demonstrate that AKR1C3 is a potential prognostic biomarker for endometrioid endometrial cancer. Full article

(This article belongs to the Special Issue Clinical Advances on Endometrial Cancer)

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Review

Jump to: Research

13 pages, 288 KiB

Open AccessReview

Fertility-Sparing Treatment of Patients with Endometrial Cancer: A Review of the Literature

by Umberto Leone Roberti Maggiore, Rola Khamisy-Farah, Nicola Luigi Bragazzi, Giorgio Bogani, Fabio Martinelli, Salvatore Lopez, Valentina Chiappa, Mauro Signorelli, Antonino Ditto and Francesco Raspagliesi

J. Clin. Med. 2021, 10(20), 4784; https://doi.org/10.3390/jcm10204784 - 19 Oct 2021

Cited by 14 | Viewed by 3533

Abstract

Endometrial cancer (EC) is currently the most common malignancy of the female genital tract in developed countries. Although it is more common in postmenopausal women, it may affect up to 25% in the premenopausal age and 3–5% under the age of 40 years. [...] Read more.

Endometrial cancer (EC) is currently the most common malignancy of the female genital tract in developed countries. Although it is more common in postmenopausal women, it may affect up to 25% in the premenopausal age and 3–5% under the age of 40 years. Furthermore, in the last decades a significant shift to pregnancy at older maternal ages, particularly in resource-rich countries, has been observed. Therefore, in this scenario fertility-sparing alternatives should be discussed with patients affected by EC. This study summarizes available literature on fertility-sparing management of patients affected by EC, focusing on the oncologic and reproductive outcomes. A systematic computerized search of the literature was performed in two electronic databases (PubMed and MEDLINE) in order to identify relevant articles to be included for the purpose of this systematic review. On the basis of available evidence, fertility-sparing alternatives are oral progestins alone or in combination with other drugs, levonorgestrel intrauterine system and hysteroscopic resection in association with progestin therapies. These strategies seem feasible and safe for young patients with G1 endometrioid EC limited to the endometrium. However, there is a lack of high-quality evidence on the efficacy and safety of fertility-sparing treatments and future well-designed studies are required. Full article

(This article belongs to the Special Issue Clinical Advances on Endometrial Cancer)

11 pages, 288 KiB

Open AccessReview

Update on Sentinel Lymph Node Biopsy in Surgical Staging of Endometrial Carcinoma

by Ane Gerda Z Eriksson, Ben Davidson, Pernille Bjerre Trent, Brynhildur Eyjólfsdóttir, Gunn Fallås Dahl, Yun Wang and Anne Cathrine Staff

J. Clin. Med. 2021, 10(14), 3094; https://doi.org/10.3390/jcm10143094 - 13 Jul 2021

Cited by 14 | Viewed by 4118

Abstract

Sentinel lymph node (SLN) biopsy has emerged as an alternative staging approach in women with assumed early-stage endometrial carcinoma. Through image-guided surgery and pathologic ultrastaging, the SLN approach is introducing “precision medicine” to the surgical management of gynecologic cancers, providing a comprehensive evaluation [...] Read more.

Sentinel lymph node (SLN) biopsy has emerged as an alternative staging approach in women with assumed early-stage endometrial carcinoma. Through image-guided surgery and pathologic ultrastaging, the SLN approach is introducing “precision medicine” to the surgical management of gynecologic cancers, providing a comprehensive evaluation of high-yield lymph nodes. This approach improves the surgeons’ ability to detect small-volume metastatic disease while reducing intraoperative and postoperative morbidity associated with lymphadenectomy. Although the majority of clinicians in Europe and the USA have recognized the value of SLN biopsy in endometrial carcinoma and introduced this as part of clinical practice, there is ongoing debate regarding its role in very low-risk patients as well as in patients at high risk of nodal metastasis. The significance of low-volume metastasis is not fully understood, and there is no consensus in regard to how the presence of isolated tumor cells should guide adjuvant therapy. Standardized protocols for histopathologic evaluation of SLNs are lacking. In this review article we aim to provide a framework for the introduction of SLN biopsy in endometrial cancer, give an updated overview of the existing literature, as well as discuss potential controversies and unanswered questions regarding this approach and future directions. Full article

(This article belongs to the Special Issue Clinical Advances on Endometrial Cancer)

32 pages, 5380 KiB

Open AccessReview

How the Gut Microbiome Links to Menopause and Obesity, with Possible Implications for Endometrial Cancer Development

by Malou P. H. Schreurs, Peggy J. de Vos van Steenwijk, Andrea Romano, Sabine Dieleman and Henrica M. J. Werner

J. Clin. Med. 2021, 10(13), 2916; https://doi.org/10.3390/jcm10132916 - 29 Jun 2021

Cited by 25 | Viewed by 7571

Abstract

Background: Interest is growing in the dynamic role of gut microbiome disturbances in human health and disease. No direct evidence is yet available to link gut microbiome dysbiosis to endometrial cancer. This review aims to understand any association between microbiome dysbiosis and [...] Read more.

Background: Interest is growing in the dynamic role of gut microbiome disturbances in human health and disease. No direct evidence is yet available to link gut microbiome dysbiosis to endometrial cancer. This review aims to understand any association between microbiome dysbiosis and important risk factors of endometrial cancer, high estrogen levels, postmenopause and obesity. Methods: A systematic search was performed with PubMed as primary database. Three separate searches were performed to identify all relevant studies. Results: Fifteen studies were identified as highly relevant and included in the review. Eight articles focused on the relationship with obesity and eight studies focused on the menopausal change or estrogen levels. Due to the heterogeneity in patient populations and outcome measures, no meta-analysis could be performed. Both the menopausal change and obesity were noted to enhance dysbiosis by reducing microbiome diversity and increasing the Firmicutes to Bacteroidetes ratio. Both also incurred estrobolome changes, leading to increased systemic estrogen levels, especially after menopause. Furthermore, microbiome dysbiosis was reported to be related to systemic inflammation through toll-like receptor signaling deficiencies and overexpression of pro-inflammatory cytokines. Conclusions: This review highlights that the female gut microbiome is intrinsically linked to estrogen levels, menopausal state and systemic inflammation, which indicates gut microbiome dysbiosis as a potential hallmark for risk stratification for endometrial cancer. Studies are needed to further define the role the gut microbiome plays in women at risk for endometrial cancer. Full article

(This article belongs to the Special Issue Clinical Advances on Endometrial Cancer)

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17 pages, 578 KiB

Open AccessReview

Fertility-Sparing Methods in Adolescents Affected by Endometrial Cancer: A Comprehensive Review

by Krzysztof Gałczyński, Piotr Olcha, Katarzyna Romanek-Piva, Maciej Jóźwik and Andrzej Semczuk

J. Clin. Med. 2021, 10(5), 1020; https://doi.org/10.3390/jcm10051020 - 02 Mar 2021

Cited by 3 | Viewed by 2010

Abstract

Although in developed countries endometrial cancer (EC) is the most common gynecological malignancy, its occurrence in adolescents is exceedingly rare. The increasing rate of obesity in children and adolescents is held responsible for the increasing prevalence of EC in younger cohorts of patients. [...] Read more.

Although in developed countries endometrial cancer (EC) is the most common gynecological malignancy, its occurrence in adolescents is exceedingly rare. The increasing rate of obesity in children and adolescents is held responsible for the increasing prevalence of EC in younger cohorts of patients. The diagnosis of this malignancy can have devastating consequences for future fertility because standard treatment protocols for EC include hysterectomy. Here, we present the first detailed review of the world literature on EC in subjects aged 21 years or younger (n = 19). The mean age at diagnosis was 16.7 ± 0.6 years. One patient (5.3%) had a Type II (high-risk) disease. No communication retrieved from the search reported on patient death; however, two (10.5%) patients were lost to follow-up. There was also a high proportion (five subjects, or 26.3%) of cases with genetic background (Cowden syndrome and Turner syndrome), therefore genetic screening or a direct genetic study should be considered in very young patients with EC. The current fertility-sparing options, limited to Type I (low-risk) disease, are presented and discussed. Such information, obtained from studies on older women, translates well to adolescent girls and very young women. Careful anatomopathological monitoring at follow-up is essential for the safety of a conservative approach. Improved survival in very young EC patients makes the preservation of fertility a central survivorship issue, therefore both patients and caregivers should undergo counseling regarding available options. Moreover, our study suggests that genetic syndromes other than Lynch syndrome may be associated with EC more frequently than previously thought. Full article

(This article belongs to the Special Issue Clinical Advances on Endometrial Cancer)

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24 pages, 2216 KiB

Open AccessReview

Mesonephric-Like Adenocarcinoma of the Endometrium: Diagnostic Advances to Spot This Wolf in Sheep’s Clothing. A Review of the Literature

by Ellen Deolet, Jo Van Dorpe and Koen Van de Vijver

J. Clin. Med. 2021, 10(4), 698; https://doi.org/10.3390/jcm10040698 - 11 Feb 2021

Cited by 25 | Viewed by 7324

Abstract

Mesonephric-like adenocarcinoma is a recently described rare neoplasm occurring in the uterine corpus and ovary. This under-recognized subtype of carcinoma can be very challenging to diagnose. In mesonephric adenocarcinoma a variety of growth patterns can be present within the same tumor, as a [...] Read more.

Mesonephric-like adenocarcinoma is a recently described rare neoplasm occurring in the uterine corpus and ovary. This under-recognized subtype of carcinoma can be very challenging to diagnose. In mesonephric adenocarcinoma a variety of growth patterns can be present within the same tumor, as a result of which they can be misinterpreted and diagnosed as low-grade endometrioid adenocarcinoma, clear cell carcinoma, or even serous carcinoma and carcinosarcoma. We report a case of mesonephric-like adenocarcinoma misdiagnosed as a low-grade endometrioid endometrial adenocarcinoma that had an early local recurrence and metastasized to the liver and the lungs. Histopathological, immunohistochemical and molecular analysis were performed and compared to published literature, providing a comprehensive overview of the current knowledge. Databases (Pubmed, Web of Science, Google Scholar) were searched with a combination of the following search terms: mesonephric-like, mesonephric, adenocarcinoma, carcinoma, uterine body, uterine corpus, endometrium. Mesonephric-like adenocarcinoma is a difficult-to-diagnose entity. Advanced diagnostics, including improved morphologic, immunohistochemical and molecular knowledge can help develop new therapeutic strategies against this specific subtype of endometrial cancer with an aggressive clinical behavior. Full article

(This article belongs to the Special Issue Clinical Advances on Endometrial Cancer)

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16 pages, 1414 KiB

Open AccessReview

Lymphedema and Post-Operative Complications after Sentinel Lymph Node Biopsy versus Lymphadenectomy in Endometrial Carcinomas—A Systematic Review and Meta-Analysis

by Rianne J.A. Helgers, Bjorn Winkens, Brigitte F.M. Slangen and Henrica M.J. Werner

J. Clin. Med. 2021, 10(1), 120; https://doi.org/10.3390/jcm10010120 - 31 Dec 2020

Cited by 23 | Viewed by 2697

Abstract

Background: Lymph node dissection (LND) is recommended as staging procedure in presumed low stage endometrial cancer. LND is associated with risk of lower-extremity lymphedema and post-operative complications. The sentinel lymph node (SLN) procedure has been shown to have high diagnostic accuracy, but [...] Read more.

Background: Lymph node dissection (LND) is recommended as staging procedure in presumed low stage endometrial cancer. LND is associated with risk of lower-extremity lymphedema and post-operative complications. The sentinel lymph node (SLN) procedure has been shown to have high diagnostic accuracy, but its effects on complication risk has been little studied. This systematic review compares the risk of lower-extremity lymphedema and post-operative complications in SLN versus LND in patients with endometrial carcinoma. Methods: A systematic search was conducted in PubMed and Cochrane Library. Results: Seven retrospective and prospective studies (total n = 3046 patients) were included. Only three studies reported the odds ratio of lower-extremity lymphedema after SLN compared to LND, which was 0.05 (95% CI 0.01–0.37; p = 0.067), 0.07 (95% CI 0.00–1.21; p = 0.007) and 0.54 (95% CI 0.37–0.80; p = 0.002) in these studies. The pooled odds ratio of any post-operative complications after SLN versus LND was 0.52 (95% CI 0.36-0.73; I² = 48%; p < 0.001). For severe post-operative complications the pooled odds ratio was 0.52 (95% CI 0.28–0.96; I² = 0%; p = 0.04). Conclusions: There are strong indications that SLN results in a lower incidence of lower-extremity lymphedema and less often severe post-operative complications compared to LND. In spite of the paucity and heterogeneity of studies, direction of results was similar in all studies, supporting the aforementioned conclusion. These results support the increasing uptake of SLN procedures in endometrial cancer. Full article

(This article belongs to the Special Issue Clinical Advances on Endometrial Cancer)

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17 pages, 2580 KiB

Open AccessReview

Diagnostic Accuracy and Clinical Impact of Sentinel Lymph Node Sampling in Endometrial Cancer at High Risk of Recurrence: A Meta-Analysis

by Lise Lecointre, Massimo Lodi, Émilie Faller, Thomas Boisramé, Vincent Agnus, Jean-Jacques Baldauf, Benoît Gallix and Chérif Akladios

J. Clin. Med. 2020, 9(12), 3874; https://doi.org/10.3390/jcm9123874 - 28 Nov 2020

Cited by 16 | Viewed by 2113

Abstract

Purpose. To assess the value of sentinel lymph node (SLN) sampling in high risk endometrial cancer according to the ESMO-ESGO-ESTRO classification. Methods. We performed a comprehensive search on PubMed for clinical trials evaluating SLN sampling in patients with high risk endometrial cancer: stage [...] Read more.

Purpose. To assess the value of sentinel lymph node (SLN) sampling in high risk endometrial cancer according to the ESMO-ESGO-ESTRO classification. Methods. We performed a comprehensive search on PubMed for clinical trials evaluating SLN sampling in patients with high risk endometrial cancer: stage I endometrioid, grade 3, with at least 50% myometrial invasion, regardless of lymphovascular space invasion status; or stage II; or node-negative stage III endometrioid, no residual disease; or non-endometrioid (serous or clear cell or undifferentiated carcinoma, or carcinosarcoma). All patients underwent SLN sampling followed by pelvic with or without para-aortic lymphadenectomy. Results. We included 17 original studies concerning 1322 women. Mean detection rates were 89% for unilateral and 68% for bilateral. Pooled sensitivity was 88.5% (95%CI: 81.2–93.2%), negative predictive value was 96.0% (95%CI: 93.1–97.7%), and false negative rate was 11.5% (95%CI: 6.8; 18.8%). We noted heterogeneity in SLN techniques between studies, concerning the tracer and its detection, the injection site, the number of injections, and the surgical approach. Finally, we found a correlation between the number of patients included and the SLN sampling performances. Discussion. This meta-analysis estimated the SLN sampling performances in high risk endometrial cancer patients. Data from the literature show the feasibility, the safety, the limits, and the impact on surgical de-escalation of this technique. In conclusion, our study supports the hypothesis that SLN sampling could be a valuable technique to diagnose lymph node involvement for patients with high risk endometrial cancer in replacement of conventional lymphadenectomy. Consequently, randomized clinical trials are necessary to confirm this hypothesis. Full article

(This article belongs to the Special Issue Clinical Advances on Endometrial Cancer)

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20 pages, 2095 KiB

Open AccessReview

Prognostic Biomarkers in Endometrial Cancer: A Systematic Review and Meta-Analysis

by Eva Coll-de la Rubia, Elena Martinez-Garcia, Gunnar Dittmar, Antonio Gil-Moreno, Silvia Cabrera and Eva Colas

J. Clin. Med. 2020, 9(6), 1900; https://doi.org/10.3390/jcm9061900 - 17 Jun 2020

Cited by 63 | Viewed by 8497

Abstract

Endometrial cancer (EC) is the sixth most common cancer in women worldwide and its mortality is directly associated with the presence of poor prognostic factors driving tumor recurrence. Stratification systems are based on few molecular, and mostly clinical and pathological parameters, but these [...] Read more.

Endometrial cancer (EC) is the sixth most common cancer in women worldwide and its mortality is directly associated with the presence of poor prognostic factors driving tumor recurrence. Stratification systems are based on few molecular, and mostly clinical and pathological parameters, but these systems remain inaccurate. Therefore, identifying prognostic EC biomarkers is crucial for improving risk assessment pre- and postoperatively and to guide treatment decisions. This systematic review gathers all protein biomarkers associated with clinical prognostic factors of EC, recurrence and survival. Relevant studies were identified by searching the PubMed database from 1991 to February 2020. A total number of 398 studies matched our criteria, which compiled 255 proteins associated with the prognosis of EC. MUC16, ESR1, PGR, TP53, WFDC2, MKI67, ERBB2, L1CAM, CDH1, PTEN and MMR proteins are the most validated biomarkers. On the basis of our meta-analysis ESR1, TP53 and WFDC2 showed potential usefulness for predicting overall survival in EC. Limitations of the published studies in terms of appropriate study design, lack of high-throughput measurements, and statistical deficiencies are highlighted, and new approaches and perspectives for the identification and validation of clinically valuable EC prognostic biomarkers are discussed. Full article

(This article belongs to the Special Issue Clinical Advances on Endometrial Cancer)

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