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Keywords = endometrial atypical hyperplasia

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16 pages, 328 KiB  
Article
A Decade of Experience in Diagnostic and Conservative Treatment of Endometrial Malignancy—Oncologic and Obstetrical Outcomes from a Referral Oncofertility Center
by Katarina Stefanovic, Jelena Dotlic, Igor Pilic, Branislav Milosevic, Olga Mihaljevic, Aleksandra Beleslin and Aleksandar Stefanović
Diagnostics 2025, 15(11), 1388; https://doi.org/10.3390/diagnostics15111388 - 30 May 2025
Viewed by 567
Abstract
Background/Objectives: This study aimed to investigate oncologic and obstetrical outcomes of patients conservatively treated for atypical hyperplasia (AH), endometrial intraepithelial neoplasm (EIN), and early endometrial cancer (EC), as well as factors that influence these outcomes. Methods: This study included 87 women conservatively [...] Read more.
Background/Objectives: This study aimed to investigate oncologic and obstetrical outcomes of patients conservatively treated for atypical hyperplasia (AH), endometrial intraepithelial neoplasm (EIN), and early endometrial cancer (EC), as well as factors that influence these outcomes. Methods: This study included 87 women conservatively treated due to AH/EIN and well-differentiated endometrioid EC confined only to the endometrium during past 10 years. Therapy type, course, and duration were registered. The response totherapy after 12 months (remission vs. disease persisting or progressing) was considered as the oncologic outcome. All attempted and achieved pregnancies, along with conception method, gestational week, and delivery type, were recorded. The obstetrical outcomes were classified as adverse (miscarriage) or successful (healthy child). Results: All patients received LNG-IUD along with GnRHa and, if indicated, metformin. Complete remission was achieved in 74.7% of patients. The disease was persisting in 17.2% and progressing in 3.5% of patients, while recurrence was registered in 4.6% of patients. Radical surgery during follow-up was indicated in 15% of patients due to condition deterioration. Pregnancy was attempted by 29.9% of patients, out of which nine succeeded (34.6%). There were two early miscarriages, while the remaining seven pregnancies ended in a term delivery of a healthy child, mostly by planned cesarean section. The only predictor of long-term disease remission was malignancy-free control histological findings. Better therapy response and achieving remission in shorter time were predictors of good obstetrical outcome. Conclusions: This study proved the efficacy and safety of current protocols for AH/EIN/EC conservative treatment and indicated that adequate early (6-month) response totherapy has the most importance for long-term remission and pregnancy achievement. Full article
(This article belongs to the Special Issue Gynecological Oncology: Advanced Diagnosis and Management in 2025)
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12 pages, 2594 KiB  
Article
Molecular Classification Guides Fertility-Sparing Treatment for Endometrial Cancer and Atypical Hyperplasia Patients
by Yiqin Wang, Linlin Bo, Xiaowei Fan, Nan Kang, Xiaobo Zhang, Li Tian, Rong Zhou and Jianliu Wang
Curr. Oncol. 2025, 32(6), 317; https://doi.org/10.3390/curroncol32060317 - 30 May 2025
Viewed by 515
Abstract
Objectives: The objective of this study was to investigate the significance of molecular classification in guiding treatment decisions for patients with endometrial cancer (EC) or atypical hyperplasia (AH) undergoing fertility-sparing treatment (FST), particularly for those with non-NSMP subtypes. Methods: We conducted a retrospective [...] Read more.
Objectives: The objective of this study was to investigate the significance of molecular classification in guiding treatment decisions for patients with endometrial cancer (EC) or atypical hyperplasia (AH) undergoing fertility-sparing treatment (FST), particularly for those with non-NSMP subtypes. Methods: We conducted a retrospective cohort study involving EC/AH patients undergoing FST and molecular classification using next-generation sequencing at Peking University People’s Hospital between June 2020 and September 2023. Results: A total of 118 EC/AH patients were included, including 92 cases with NSMP, 11 with MMRd, 11 with POLEmut, and 4 with p53abn. (1) Of the 11 patients with MMRd, 6 achieved a complete response (CR) with 1 case receiving progestin, 3 cases showed insensitivity to the initial progestin before transitioning to a combined regimen of progestin and a PD-1 inhibitor, and 2 cases initially received progestin plus a PD-1 inhibitor. There were no significant differences in the cumulative CR rates between the MMRd and NSMP subgroups but a trend of a lower relapse-free-survival (RFS) rate for the MMRd subgroup (p = 0.074). (2) Of the 11 cases with POLEmut, 10 achieved CR but 4 relapsed. There was also a trend for a lower RFS rate in the POLEmut patients (p = 0.069) compared with the NSMP subgroup. (3) Three of the four patients with p53mut achieved CR after treatment with the GnRHa plus LNG-IUS regimen. Conclusion: The selection of appropriate regimens may improve FST outcomes in EC/AH patients with molecular classification of non-NSMP subtypes. Immunotherapy is an effective fertility-preserving approach for patients with MMRd. Full article
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12 pages, 4516 KiB  
Article
Expression Characteristics of 3-Marker Panel (PAX2, PTEN, and β-Catenin) in Benign Interval and Secretory Endometrium and Secretory Endometrial Precancer
by Shuang Niu, Kyle Molberg, Jackson Chen, Lesley Conrad, Elena Lucas and Hao Chen
Cancers 2025, 17(9), 1495; https://doi.org/10.3390/cancers17091495 - 29 Apr 2025
Viewed by 682
Abstract
Background/Objectives: Despite advancements in treatment options, endometrial cancer remains a significant threat to women, underscoring the importance of early detection of atypical hyperplasia/endometrioid intraepithelial neoplasia (AH/EIN), the widely accepted histological precursor to endometrial carcinoma. Even with refinements in morphological criteria for the [...] Read more.
Background/Objectives: Despite advancements in treatment options, endometrial cancer remains a significant threat to women, underscoring the importance of early detection of atypical hyperplasia/endometrioid intraepithelial neoplasia (AH/EIN), the widely accepted histological precursor to endometrial carcinoma. Even with refinements in morphological criteria for the diagnosis of AH/EIN, accurate diagnosis remains challenging for pathologists, particularly in cases with secretory changes. Morphological alterations resulting from secretory-related changes further complicate the application of diagnostic criteria, emphasizing the need for reliable biomarkers. Previous studies have demonstrated that a panel consisting of three immunohistochemical markers, PAX2, PTEN, and β-catenin, can be effectively utilized for the identification of AH/EIN in various non-secretory scenarios. Methods: In this study, a total of 69 AH/EIN within secretory endometrium were analyzed using this panel. Benign interval endometrium (n = 57) and secretory phase endometrium (n = 71) were also analyzed for PAX2, PTEN, and β-catenin expression as controls. Results: The 3-marker panel successfully identified 93% of secretory AH/EIN, comparable to its performance in identifying non-secretory bona fide AH/EIN (92.8%) and AH/EIN within endometrial polyps (92.4%). Of note, β-catenin expression in benign interval endometrium commonly displayed weak nuclear staining (67%), which could pose a diagnostic pitfall when using the 3-marker panel. Overall, the results demonstrate the diagnostic utility of the 3-marker panel in clinical practice in identifying AH/EIN within challenging secretory phase endometrium cases. Conclusions: Combined with previous research highlighting its effectiveness in other challenging contexts—such as AH/EIN in polyps, small-sized EIN (subdiagnostic EIN), and progestin-treated EIN—this study provides strong evidence supporting the panel’s broad applicability in resolving major diagnostic challenges related to the precise diagnosis of AH/EIN. Full article
(This article belongs to the Special Issue Biomarkers for Gynecological Cancers)
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18 pages, 2517 KiB  
Article
The Application of Liquid Biopsy for the Development and Validation of a Non-Invasive Screening and Diagnosis Test for Endometrial Premalignant and Malignant Lesions: A Prospective Innovative Pilot Study
by Giuseppina Esposito, Giuseppe D’Angelo, Luigia De Falco, Eloisa Evangelista, Giovanni Savarese, Antonio Fico, Federica Cinque, Pierluigi Giampaolino, Attilio Di Spiezio Sardo, Giuseppe Bifulco and Luigi Della Corte
Cancers 2025, 17(7), 1078; https://doi.org/10.3390/cancers17071078 - 23 Mar 2025
Viewed by 790
Abstract
Background/Objectives: Endometrial cancer (EC) is a common malignancy in developed countries, with incidence closely linked to lifestyle factors and genetic predispositions, notably Lynch syndrome. Traditional biopsy methods for diagnosis and monitoring are invasive. This study aims to develop and validate a non-invasive [...] Read more.
Background/Objectives: Endometrial cancer (EC) is a common malignancy in developed countries, with incidence closely linked to lifestyle factors and genetic predispositions, notably Lynch syndrome. Traditional biopsy methods for diagnosis and monitoring are invasive. This study aims to develop and validate a non-invasive diagnostic method for EC using liquid biopsy, specifically examining circulating tumor DNA (ctDNA) for its potential in early detection and disease monitoring. Methods: A cohort of 63 patients with EC or atypical endometrial hyperplasia (AEH) was recruited from the Gynecological Unit of the Azienda Ospedaliera Universitaria Federico II. Plasma samples were processed to extract ctDNA, which was sequenced and analyzed for mutations. Matched tumor tissue and germline DNA were also examined to confirm mutation concordance and assess potential genetic predispositions. Results: Pathogenic mutations were identified in plasma ctDNA in 59 out of 63 cases (93%), with a 65% concordance between plasma ctDNA mutations and those found in solid tumor samples. Key mutations in genes such as PTEN, PIK3R1, and KMT2C were significantly associated with a higher tumor grade and advanced stage disease, such as myometrial infiltration. Conclusions: Liquid biopsy shows promise as a minimally invasive diagnostic and monitoring tool for EC, offering real-time insights into tumor biology. The high mutation concordance between the plasma ctDNA and tumor tissue underscores the potential of a liquid biopsy in managing EC, particularly for patients at risk of recurrence. Further longitudinal studies are needed to establish ctDNA as a standard tool in EC diagnosis and monitoring. Full article
(This article belongs to the Special Issue Endometrial Cancer—Diagnosis and Treatment)
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9 pages, 502 KiB  
Review
Sentinel Lymph Node in Endometrial Hyperplasia: State of the Art and Future Perspectives
by Valentina Billone, Lina De Paola, Eleonora Conti, Letizia Borsellino, Zoltan Kozinszky, Pierluigi Giampaolino, Andrea Suranyi, Luigi Della Corte, Alessandra Andrisani, Gaspare Cucinella, Susanna Marinelli and Giuseppe Gullo
Cancers 2025, 17(5), 776; https://doi.org/10.3390/cancers17050776 - 24 Feb 2025
Cited by 1 | Viewed by 893
Abstract
Background/Objectives: Endometrial hyperplasia is a uterine pathology characterized by the abnormal proliferation of endometrial glands, resulting in an increased gland-to-stroma ratio. Complex atypical hyperplasia represents the primary precursor to endometrial cancer. Given the high risk of progression to endometrial adenocarcinoma, the accurate [...] Read more.
Background/Objectives: Endometrial hyperplasia is a uterine pathology characterized by the abnormal proliferation of endometrial glands, resulting in an increased gland-to-stroma ratio. Complex atypical hyperplasia represents the primary precursor to endometrial cancer. Given the high risk of progression to endometrial adenocarcinoma, the accurate diagnosis and classification of endometrial hyperplasia are crucial. Since the treatment for atypical endometrial hyperplasia is the same as that for early-stage endometrial cancer (i.e., total hysterectomy and bilateral salpingo-oophorectomy), researchers have questioned whether sentinel lymph node mapping could also have a prognostic role in atypical endometrial hyperplasia. Methods: A literature search was conducted in PubMed and Scopus from 2014 to 2025. Of the 65 papers found, 31 relevant articles were selected based on inclusion criteria, focusing on sentinel lymph node staging in patients with atypical endometrial hyperplasia. This review aims to assess whether sentinel lymph node mapping can be routinely used for prognostic and therapeutic purposes in clinical practice. Results: Sentinel lymph node biopsy represents a promising diagnostic technique for patients with atypical endometrial hyperplasia, reducing the need for invasive procedures and postoperative risks. However, its application requires advanced surgical skills and access to specific technologies, raising ethical and financial concerns, while future studies could improve patient selection and the reliability of the procedure through technological innovations. Conclusions: Sentinel lymph node biopsy is a safe and effective method for staging early-stage endometrial cancer and atypical hyperplasia, with low metastasis rates, but future research should focus on identifying patients who would benefit most from this procedure, considering its costs and required expertise. Full article
(This article belongs to the Special Issue Diagnoses and Treatments of Metastatic Endometrial Cancer)
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12 pages, 572 KiB  
Article
Robotic Surgery in Severely Obese Frail Patients for the Treatment of Atypical Endometrial Hyperplasia and Endometrial Cancer: A Propensity-Match Analysis at an ESGO-Accredited Center
by Martina Arcieri, Federico Paparcura, Cristina Giorgiutti, Cristina Taliento, Giorgio Bogani, Lorenza Driul, Pantaleo Greco, Alfredo Ercoli, Vito Chiantera, Francesco Fanfani, Anna Fagotti, Giovanni Scambia, Andrea Mariani, Stefano Restaino and Giuseppe Vizzielli
Cancers 2025, 17(3), 482; https://doi.org/10.3390/cancers17030482 - 1 Feb 2025
Cited by 4 | Viewed by 934
Abstract
Background and Objectives: Robotic-assisted laparoscopy (RS) has been widely adopted for the management of endometrial cancer (EC) due to favorable perioperative outcomes, especially in the context of obesity, which is an established risk factor for EC. This study retrospectively evaluated the perioperative outcomes [...] Read more.
Background and Objectives: Robotic-assisted laparoscopy (RS) has been widely adopted for the management of endometrial cancer (EC) due to favorable perioperative outcomes, especially in the context of obesity, which is an established risk factor for EC. This study retrospectively evaluated the perioperative outcomes of RS versus conventional laparoscopy (LS) in treating EC and atypical endometrial hyperplasia (AH). Methods: Between November 2021 and October 2023, 138 patients with AH or EC underwent surgery at the Clinic of Obstetric and Gynecological—Azienda Sanitaria Universitaria Friuli Centrale, Udine. All patients had total hysterectomy with bilateral salpingo-oophorectomy, with or without lymphadenectomy or sentinel lymph node biopsy. The study included 62 patients treated with LS and 62 with RS. Results: The median BMI was higher in the RS group (35.5 vs. 24 kg/m2, p = 0.001). There was no significant difference in operative time between the laparoscopic group and the robotic console time (median 130 vs. 130 min, p = 0.131). No significant differences were found in terms of blood loss, conversion to laparotomy, intraoperative complications, hospital stay, or early postoperative complications between the two groups. Conclusions: Our data confirm the feasibility of robotic surgery in obese patients, allowing surgical results comparable to those of laparoscopy in normal-weight patients. Full article
(This article belongs to the Section Methods and Technologies Development)
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14 pages, 1552 KiB  
Article
PCOS Influences the Expression of AMHRII in the Endometrium of AEH During the Reproductive Age
by Yingsha Yao, Shulan Zhu and Xiaoming Zhu
Diagnostics 2024, 14(24), 2872; https://doi.org/10.3390/diagnostics14242872 - 20 Dec 2024
Viewed by 892
Abstract
Background: Endometrial proliferative lesions (EPLs) encompass endometrial hyperplasia (EH) and endometrial carcinoma (EC). Atypical endometrial hyperplasia (AEH) is associated with an elevated risk of progression to EC. Patients with polycystic ovarian syndrome (PCOS) exhibit higher serum levels of anti-Müllerian hormone (AMH) and a [...] Read more.
Background: Endometrial proliferative lesions (EPLs) encompass endometrial hyperplasia (EH) and endometrial carcinoma (EC). Atypical endometrial hyperplasia (AEH) is associated with an elevated risk of progression to EC. Patients with polycystic ovarian syndrome (PCOS) exhibit higher serum levels of anti-Müllerian hormone (AMH) and a correspondingly increased incidence of EPLs. AMH has the capacity to inhibit the cell proliferation of EPLs derived from Müllerian duct tissue through the AMH-AMH receptor (AMHR) signaling pathway. Methods: Pairs of samples matched by preference scores were randomly selected. Immunohistochemistry was employed to assess the expression levels of AMHR type II (AMHR2) in endometrial tissue. A comparative analysis was performed between tissues from individuals with PCOS and those without, as well as between a normal endometrium and endometrial tissue from individuals with EPLs. This study aimed to elucidate differences in AMHR2 expression among these tissue types. By focusing on AMHR2 expression, the impact of the PCOS-related background on the endometrial AMH-AMHR cascade signaling pathway was initially investigated. Results: The AMHR2 protein was expressed in the endometrium of both the PCOS group and the non-PCOS group during the reproductive age (20–39 years). The expression of the AMHR2 protein in the AEH endometrium of PCOS patients did not differ significantly from that in the normal endometrium of PCOS patients; however, it was significantly higher than in the AEH endometrium of non-PCOS patients (p = 0.011). Conversely, the expression of the AMHR2 protein in the AEH endometrium of non-PCOS patients was significantly lower than that in the normal endometrium of non-PCOS patients (p = 0.021). Notably, there was no significant difference in AMHR2 protein expression in a normal endometrium between PCOS and non-PCOS patients. Conclusions: The involvement of the endometrial AMH-AMHR cascade signaling pathway and its biological effects in the pathogenesis of AEH are evident. The pathophysiological conditions associated with PCOS, such as elevated serum AMH levels and other pathological states, may directly or indirectly influence the AMH-AMHR cascade signaling pathway in the endometrium. This influence could contribute to the progression of AEH. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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8 pages, 10293 KiB  
Case Report
A Case Report of the Synchronous Occurrence of Ovarian Granulosa Cell Tumour and Malignant Endometrial Polyp with Immunohistochemical Expression of Hormone Receptors and Biomarkers p-53 and Ki-67
by Krum Vladov, Ekaterina Uchikova, Maria Koleva-Ivanova, Kamen Yamakov, Veselin Belovezhdov, Gita Yamakova-Vladova and Eleonora Hristova-Atanasova
Reports 2024, 7(4), 103; https://doi.org/10.3390/reports7040103 - 20 Nov 2024
Viewed by 1138
Abstract
Background and Clinical Significance: Abnormal uterine bleeding during the postmenopausal years is a pathological sign that may be due to simultaneous intrauterine and ovarian pathology. Granulosa cell tumours of the ovary are malignant neoplasms producing oestradiol, which leads to the abnormal proliferation of [...] Read more.
Background and Clinical Significance: Abnormal uterine bleeding during the postmenopausal years is a pathological sign that may be due to simultaneous intrauterine and ovarian pathology. Granulosa cell tumours of the ovary are malignant neoplasms producing oestradiol, which leads to the abnormal proliferation of the endometrium, precancerous lesions, and endometrial carcinoma type I. Case Presentation: The authors present a clinical case of a 67-year-old woman with postmenopausal bleeding who underwent a total abdominal hysterectomy with bilateral adnexectomy, pelvic lymphadenectomy, and partial omentectomy. The histopathological examination showed a granulosa cell adult-type ovarian tumour and a malignant endometrial polyp with atypical hyperplasia of the endometrium. Conclusions: The immunohistochemical analysis of the malignant endometrial polyp confirmed the expression of oestrogen, progesterone receptors, and the biomarker Ki-67. Full article
(This article belongs to the Special Issue Case Reports in Obstetrics and Gynecology)
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21 pages, 601 KiB  
Review
Endometrial Atypical Hyperplasia and Risk of Endometrial Cancer
by An-Ju Chou, Ruo-Shi Bing and Dah-Ching Ding
Diagnostics 2024, 14(22), 2471; https://doi.org/10.3390/diagnostics14222471 - 5 Nov 2024
Cited by 5 | Viewed by 7921
Abstract
Endometrial atypical hyperplasia (EAH) is a premalignant condition with a substantial risk of progression to endometrial cancer (EC), with the endometrioid subtype being the most common. EAH is characterized by abnormal endometrial gland proliferation and cellular atypia, often resulting from prolonged unopposed estrogen [...] Read more.
Endometrial atypical hyperplasia (EAH) is a premalignant condition with a substantial risk of progression to endometrial cancer (EC), with the endometrioid subtype being the most common. EAH is characterized by abnormal endometrial gland proliferation and cellular atypia, often resulting from prolonged unopposed estrogen exposure. This review aims to explore the clinical significance of EAH, its risk of progression to EC, and the current approaches to management. The risk of EAH progressing to EC ranges from 20 to 50%, influenced by factors such as histopathology and genetic mutations including PTEN and KRAS. Key risk factors include obesity, polycystic ovary syndrome, and postmenopausal status. Abnormal uterine bleeding is a hallmark symptom of EAH and early-stage EC, necessitating diagnostic evaluation through endometrial biopsy and transvaginal ultrasonography. Therapeutic management strategies depend on patient risk and fertility considerations. Hormonal therapy, particularly progestins, is the mainstay for fertility preservation, while hysterectomy is preferred for higher-risk patients. Regular monitoring with biopsies is essential for those undergoing conservative treatment. Recent advancements in the management of EAH and EC have shifted towards incorporation of molecular diagnostics and targeted therapies, enabling better risk stratification and individualized care. Biomarkers and minimally invasive surgical techniques are emerging as promising approaches in improving outcomes for women with EAH. This review underscores the importance of early diagnosis and personalized management in preventing the progression of EAH to EC, highlighting current clinical practices and potential future developments in this field. Full article
(This article belongs to the Special Issue Advances in Diagnosis of Gynecological Cancers)
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10 pages, 880 KiB  
Article
SIR-EN—New Biomarker for Identifying Patients at Risk of Endometrial Carcinoma in Abnormal Uterine Bleeding at Menopause
by Carlo Ronsini, Irene Iavarone, Maria Giovanna Vastarella, Luigi Della Corte, Giada Andreoli, Giuseppe Bifulco, Luigi Cobellis and Pasquale De Franciscis
Cancers 2024, 16(21), 3567; https://doi.org/10.3390/cancers16213567 - 23 Oct 2024
Cited by 8 | Viewed by 1523
Abstract
Objective: This study aimed to evaluate the efficacy of a new biomarker, termed SIR-En, in identifying patients at risk of endometrial carcinoma among those presenting with abnormal uterine bleeding during menopause. Material and Methods: A retrospective case–control analysis was conducted on 242 women [...] Read more.
Objective: This study aimed to evaluate the efficacy of a new biomarker, termed SIR-En, in identifying patients at risk of endometrial carcinoma among those presenting with abnormal uterine bleeding during menopause. Material and Methods: A retrospective case–control analysis was conducted on 242 women with menopausal abnormal uterine bleeding and endometrial thickness ≥ 4 mm. Peripheral blood samples were collected within 7 days before histological diagnosis. systemic inflammatory reaction (SIR) indices were calculated, including NLR, MLR, PLR, and SII. SIR-En was derived by multiplying SII and endometrial thickness. Statistical analyses, including multivariate linear regression and ROC curve analysis, were performed to assess the diagnostic capability of SIR-En. Results: Patients were categorized into endometrial hyperplasia (50 patients) and endometrial cancer (192 patients) groups. The SIR-En index was significantly higher in the carcinoma group (8710 vs. 6420; p = 0.003). The ROC curve for SIR-En had an AUC of 0.6351 (95% CI: 0.5579–0.7121). Using Youden’s method, the optimal SIR-En cutoff was 13,806, showing a specificity of 0.940 and a positive predictive value of 0.957. Conclusions: Combining systemic inflammatory indices with endometrial thickness, the SIR-En index can effectively distinguish between endometrial hyperplasia and carcinoma in menopausal women with abnormal uterine bleeding. Despite the retrospective design, the identified cutoff’s high specificity and positive predictive value support its potential utility in clinical practice. Further prospective studies are required to validate these findings and optimize clinical application. Full article
(This article belongs to the Special Issue Fertility Preservation in Gynecological Cancer)
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19 pages, 6939 KiB  
Article
Quantitative Assessment of Polarization and Elastic Properties of Endometrial Tissue for Precancer/Cancer Diagnostics Using Multimodal Optical Coherence Tomography
by Anton A. Plekhanov, Gennady O. Grechkanev, Elena A. Avetisyan, Maria M. Loginova, Elena B. Kiseleva, Anastasia A. Shepeleva, Alexander A. Moiseev, Alexander A. Sovetsky, Ekaterina V. Gubarkova, Anastasia A. Anina, Angelina M. Shutova, Sergey V. Gamayunov, Grigory V. Gelikonov, Vladimir Y. Zaitsev, Marina A. Sirotkina and Natalia D. Gladkova
Diagnostics 2024, 14(19), 2131; https://doi.org/10.3390/diagnostics14192131 - 25 Sep 2024
Cited by 3 | Viewed by 1491
Abstract
Objectives: The most important phase in the endometrial pathologies diagnostics is the histological examination of tissue biopsies obtained under visual hysteroscopic control. However, the unclear visual diagnostics characteristics of subtle focal endometrial pathologies often lead to selection errors regarding suspicious endometrial lesions [...] Read more.
Objectives: The most important phase in the endometrial pathologies diagnostics is the histological examination of tissue biopsies obtained under visual hysteroscopic control. However, the unclear visual diagnostics characteristics of subtle focal endometrial pathologies often lead to selection errors regarding suspicious endometrial lesions and to a subsequent false pathological diagnosis/underestimation of precancer or early-stage cancer. Methods: In this study, we investigate the potential of Multimodal Optical Coherence Tomography (MM OCT) to verify suspicious endometrial lesion regions before biopsy collection. We study the polarization (by cross-polarization OCT, CP OCT) and elastic (by compression OCT-elastography, C-OCE) properties of ex vivo endometrial tissue samples in normal conditions (proliferative and secretory phases to the menstrual cycle, atrophic endometrium) with endometrial hyperplasia (non-atypical and endometrial intraepithelial neoplasia) and endometrial cancer subtypes (low-grade, high-grade, clear cell and serous). Results: To the best of our knowledge, this is the first quantitative assessment of relevant OCT parameters (depth-resolved attenuation coefficient in co-[Att(co) values] and cross-[(Att(cross) values] polarizations and Young’s elastic modulus [stiffness values]) for the selection of the most objective criteria to identify the clinically significant endometrial pathologies: endometrial intraepithelial neoplasia and endometrial cancer. The study demonstrates the possibility of detecting endometrial pathologies and establishing optimal threshold values of MM OCT criteria for the identification of endometrial cancer using CP OCT (by Att(co) values = 3.69 mm−1, Sensitivity (Se) = 86.1%, Specificity (Sp) = 92.6%; by Att(cross) values = 2.27 mm−1, Se = 86.8%, Sp = 87.0%) and C-OCE (by stiffness values = 122 kPa, Se = 93.2%, Sp = 91.1%). The study also differentiates endometrial intraepithelial neoplasia from non-atypical endometrial hyperplasia and normal endometrium using C-OCE (by stiffness values = 95 kPa, Se = 87.2%, Sp = 90.1%). Conclusions: The results are indicative of the efficacy and potential of clinical implementation of in vivo hysteroscopic-like MM OCT in the diagnosis of endometrial pathologies. Full article
(This article belongs to the Special Issue Imaging for the Diagnosis of Obstetric and Gynecological Diseases)
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12 pages, 890 KiB  
Article
Expression Patterns of Cytokeratins (CK7, CK20, CK19, CK AE1/AE3) in Atypical Endometrial Hyperplasia Coexisting with Endometrial Cancer
by Danuta Vasilevska, Vilius Rudaitis, Dorota Lewkowicz, Dominika Širvienė, Ugnius Mickys, Marek Semczuk, Bogdan Obrzut and Andrzej Semczuk
Int. J. Mol. Sci. 2024, 25(16), 9084; https://doi.org/10.3390/ijms25169084 - 21 Aug 2024
Cited by 2 | Viewed by 2488
Abstract
Few studies have evaluated cytokeratin’s (CK) staining patterns in atypical endometrial hyperplasia (AEH) coexisting with early-stage endometrial cancer (EC). We aimed to assess the staining patterns of selected CKs (CK7, CK19, CK20, CK AE1/AE3) in 74 patients with coexisting AEH and EC by [...] Read more.
Few studies have evaluated cytokeratin’s (CK) staining patterns in atypical endometrial hyperplasia (AEH) coexisting with early-stage endometrial cancer (EC). We aimed to assess the staining patterns of selected CKs (CK7, CK19, CK20, CK AE1/AE3) in 74 patients with coexisting AEH and EC by independently analyzing both morphological variables. Specimens were collected from women with AEH and EC who underwent surgical interventions between 2012 and 2019 at the Department of Obstetrics and Gynecology of Vilnius University Hospital “Santaros Klinikos” in Vilnius, Lithuania. Immunostaining was also qualitatively classified as being heterogeneous or intense. The results revealed heterogeneous CK7 expression in all AEH cases and intense staining in 95.95% cases of AEH. The heterogeneous expression of CK7 was detected in all EC specimens. Intense CK7 expression was observed in 95.09% cases of EC G1 and in all G2 ECs. Heterogenous CK19 expression was present in all AEH specimens with intense staining in 92.42% of cases. Heterogeneous CK19 expression was observed in all EC samples with intense expression in 86.27% cases of EC G1 and 100% cases of EC G2. Interestingly, a significant relationship was found when comparing the heterogeneous expression of CK19 between AEH and well-differentiated EC. A significant difference was reported in the intense expression of CK AE1/AE3 (p = 0.031; p = 0.029) between AEH and G2 ECs and in the intense expression of CK AE1/AE3 between G1 and G2 ECs. CK20 staining was not a characteristic feature for AEH and early-stage EC. CK staining is present either in AEH or in early-stage endometrioid-subtype EC in different manners. Heterogeneous CK19 expression was significantly more common in AEH than in EC. CK20 expression was not associated with either AEH nor early-stage EC. An intense expression of CK AE1/AE3 was mainly present in moderately differentiated ECs, whereas the intense reactivity of AE1/AE3 showed a significant difference in well to moderately differentiated uterine tumors. The clinical implication of CK staining may aid in the more accurate diagnosis of AEH and early-stage EC as well as detect micrometastases leading to better oncological outcomes. Full article
(This article belongs to the Special Issue Recent Advances in Endometrial Cancer)
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15 pages, 4234 KiB  
Article
Fractal Dimension, Circularity, and Solidity of Cell Clusters in Liquid-Based Endometrial Cytology Are Potentially Useful for Endometrial Cancer Detection and Prognosis Prediction
by Toshimichi Onuma, Akiko Shinagawa, Tetsuji Kurokawa, Makoto Orisaka and Yoshio Yoshida
Cancers 2024, 16(13), 2469; https://doi.org/10.3390/cancers16132469 - 6 Jul 2024
Viewed by 1872
Abstract
Endometrial cancer (EC) in women is increasing globally, necessitating improved diagnostic methods and prognosis prediction. While endometrial histology is the conventional approach, liquid-based endometrial cytology may benefit from novel analytical techniques for cell clusters. A clinical study was conducted at the University of [...] Read more.
Endometrial cancer (EC) in women is increasing globally, necessitating improved diagnostic methods and prognosis prediction. While endometrial histology is the conventional approach, liquid-based endometrial cytology may benefit from novel analytical techniques for cell clusters. A clinical study was conducted at the University of Fukui Hospital from 2012 to 2018, involving 210 patients with endometrial cytology. The liquid-based cytology images were analyzed using cell cluster analysis with Image J software. Logistic regression, ROC analysis, and survival analysis were employed to assess the diagnostic accuracy and prognosis between cell cluster analysis and EC/atypical endometrial hyperplasia (AEH). Circularity and fractal dimension demonstrated significant associations with EC and AEH, regardless of age and cytology results. The ROC analysis revealed improved diagnostic accuracy when combining fractal dimension with cytology, particularly in menopausal age groups. Lower circularity and solidity were independently associated with poor overall survival, while higher fractal dimension values correlated with poorer overall survival in Grades 2 and 3 endometrial cancers. The combination of circularity and fractal dimension with cytology improved diagnostic accuracy for both EC and AEH. Moreover, circularity, solidity, and fractal dimension may serve as prognostic indicators for endometrial cancer, contributing to the development of more refined screening and diagnostic strategies. Full article
(This article belongs to the Section Cancer Causes, Screening and Diagnosis)
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11 pages, 264 KiB  
Article
Evaluation of Sentinel Lymph Nodes in Complex Atypical Endometrial Hyperplasia
by Hala Al Kallas, Pamela Cooper, Shruti Varma, Jenna Peplinski, Yen-Hong Kuo, Brianna Miller, Noelle Aikman, Mark Eliot Borowsky, Ashley Haggerty and Karim ElSahwi
Lymphatics 2024, 2(2), 97-107; https://doi.org/10.3390/lymphatics2020008 - 22 May 2024
Cited by 3 | Viewed by 1847
Abstract
Complex atypical endometrial hyperplasia (CAH) carries a high probability of cancer. The intraoperative evaluation of endometrial cancer in cases of CAH has not been reliable. The safety and sensitivity of sentinel lymph node (SLN) sampling has been validated. In our study, we aimed [...] Read more.
Complex atypical endometrial hyperplasia (CAH) carries a high probability of cancer. The intraoperative evaluation of endometrial cancer in cases of CAH has not been reliable. The safety and sensitivity of sentinel lymph node (SLN) sampling has been validated. In our study, we aimed to evaluate the efficacy and safety of SLN sampling in CAH managed by the da Vinci robotic platform. A total of 113 patients with a preoperative diagnosis of CAH were included in this retrospective cohort study. All of them underwent a robot-assisted total laparoscopic hysterectomy and bilateral salpingo-oophorectomy, with 69 patients undergoing SLN sampling. A statistical analysis calculated the probability of cancer, the SLN map rate, and surgical complications. The predictors of cancer were evaluated. Descriptive statistics were used to summarize the results; comparative statistics were used to compare the cohorts; and logistical regression analysis was used to predict the risk. Forty-seven percent of the entire cohort was diagnosed with endometrial cancer. The median age was 63 years in the SLN cohort (N = 69) and 61 in the No-SLN cohort (N = 44) (p = 0.363). The median BMI was 34 Kg/m2 in the SLN cohort and 40 in the No-SLN cohort (p = 0.004). The bilateral SLN map was 92.8%, and the unilateral SLN map rate was 7.2%. There were no grade-3–4 complications in the SLN cohort, and four grade-3–4 complications in the No-SLN group (p = 0.021). A preoperative diagnosis of CAH bordering on or unable to rule out cancer was the only predictor of cancer. Sentinel lymph node sampling has a high map rate and low complications in CAH. We recommend a prospective study investigating the clinical benefit of the procedure. Full article
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Article
Analysis of CDO1, PITX2, and CDH13 Gene Methylation in Early Endometrial Cancer for Prediction of Medical Treatment Outcomes
by Aleksey M. Krasnyi, Lyubov T. Gadzhieva, Diana N. Kokoeva, Mark G. Kosenko, Ekaterina L. Yarotskaya, Stanislav V. Pavlovich, Levon A. Ashrafyan and Gennady T. Sukhikh
Int. J. Mol. Sci. 2024, 25(9), 4892; https://doi.org/10.3390/ijms25094892 - 30 Apr 2024
Cited by 3 | Viewed by 1975
Abstract
An observational cohort study of patients diagnosed with endometrial cancer (EC) stage IA G1, or atypical endometrial hyperplasia (AEH), undergoing organ-preserving treatment, was conducted. Objective of the study: To determine CDO1, PITX2, and CDH13 gene methylation levels in early endometrial cancer [...] Read more.
An observational cohort study of patients diagnosed with endometrial cancer (EC) stage IA G1, or atypical endometrial hyperplasia (AEH), undergoing organ-preserving treatment, was conducted. Objective of the study: To determine CDO1, PITX2, and CDH13 gene methylation levels in early endometrial cancer and atypical hyperplasia specimens obtained before organ-preserving treatment in the patients with adequate response and with insufficient response to hormonal treatment. Materials and methods: A total of 41 endometrial specimens obtained during diagnostic uterine curettage in women with EC (n = 28) and AEH (n = 13), willing to preserve reproductive function, were studied; 18 specimens of uterine cancer IA stage G1 from peri- and early postmenopausal women (comparison group) were included in the study. The control group included 18 endometrial specimens from healthy women obtained by diagnostic curettage for missed abortion and/or intrauterine adhesions. Methylation levels were analyzed using the modified MS-HRM method. Results: All 13 women with AEH had a complete response (CR) to medical treatment. In the group undergoing organ-preserving treatment for uterine cancer IA stage G1 (n = 28), 14 patients had a complete response (EC CR group) and 14 did not (EC non-CR group). It was found that all groups had statistically significant differences in CDO1 gene methylation levels compared to the control group (p < 0.001) except for the EC CR group (p = 0.21). The p-value for the difference between EC CR and EC non-CR groups was <0.001. The differences in PITX2 gene methylation levels between the control and study groups were also significantly different (p < 0.001), except for the AEH group (p = 0.21). For the difference between EC CR and EC non-CR groups, the p-value was 0.43. For CDH13 gene methylation levels, statistically significant differences were found between the control and EC non-CR groups (p < 0.001), and the control and EC comparison groups (p = 0.005). When comparing the EC CR group with EC non-CR group, the p-value for this gene was <0.001. The simultaneous assessment of CDO1 and CDH13 genes methylation allowed for an accurate distinction between EC CR and EC non-CR groups (AUC = 0.96). Conclusion: The assessment of CDO1 and CDH13 gene methylation in endometrial specimens from patients with endometrial cancer (IA stage G1), scheduled for medical treatment, can predict the treatment outcome. Full article
(This article belongs to the Special Issue Molecular Advances in Gynecologic Cancer)
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