Endometrial Adenocarcinoma Research Articles

Abstract 7061: Targeting metabolic vulnerabilities in ARID1A/B dual-deficient dedifferentiated endometrial carcinoma

Abstract Background: Dedifferentiated endometrial carcinoma (DDEC) is an aggressive endometrial carcinoma defined histologically by undifferentiated carcinoma juxtaposed against stage 1 or 2 endometrial adenocarcinoma. DDEC responds poorly to conventional platinum/taxane-based chemotherapy, particularly in the case of extrauterine spread. This highlights a need to develop novel therapies for individuals with DDEC. Genetically, a third of DDEC cases have co-inactivating mutations of ARID1A and ARID1B. These genes encode core subunits of the sucrose/switch non-fermentable (SWI/SNF) complex that regulate transcription. Furthermore, dual loss of ARID1A/B is believed to play a role in driving DDEC tumor development. We hypothesize that ARID1A/B dual-deficiency in DDEC generates unique genetic deficiencies that allow for the development of novel therapies for this cancer. We approached this hypothesis by first conducting a preliminary analysis of the Cancer Dependency Map (DepMap), which has identified vulnerabilities in mitochondrial functioning in ARID1A/B dual-deficient DDECs. As such, we aimed to understand the role of mitochondrial oxidative phosphorylation (OXPHOS) and redox homeostasis in ARID1A/B dual-deficient DDEC to create new treatment options. Methods: A panel of ARID1A/B dual-deficient and proficient endometrial cancer cell lines were treated with OXPHOS inhibitor IACS-010759 and reactive oxidative species (ROS)-inducing agent elesclomol to identify shifts in drug response between the two groups. To account for genomic differences between the cell lines, we also treated an ARID1B knock-out isogeneic cell line with the drugs. Additionally, changes in metabolism in the endometrial cancer cell lines were measured using Seahorse metabolic flux assays to determine if ARID1A/B dual-deficient cell lines have an increased dependency on OXPHOS for cell growth. Results: While the Seahorse assays revealed no significant difference in OXPHOS and glycolysis activities between the two groups, drug sensitivity assays demonstrated that ARID1A/B dual-deficient cancers are more sensitive to OXPHOS inhibition and increased ROS production than the proficient cell lines. Depletion of ARID1B in an ARID1A deficient cell line sensitizes the cells to both drugs. Furthermore, IACS-010759 significantly suppressed the growth of ARID1A/B-deficient DDEC xenograft tumor growth. Conclusion: ARID1A/B-dual deficient cancer cells rely on mitochondria function for survival. The underlying mechanisms are currently under investigation. Citation Format: Rebecca Ho, Eunice Li, Chae Young Shin, Shary Chen, David Huntsman, Yemin Wang. Targeting metabolic vulnerabilities in ARID1A/B dual-deficient dedifferentiated endometrial carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7061.

A Study on the Biological Activity of Optically Pure Aziridine Phosphines and Phosphine Oxides.

A series of optically pure aziridine phosphines and their corresponding phosphine oxides were synthesized through established chemical methodologies. The compounds were systematically investigated for their biological properties. Notably, all synthesized compounds demonstrated moderate antibacterial activity only against the reference strain of Staphylococcus aureus. However, compounds 5 and 7 exhibited noteworthy cell viability inhibition of human cervical epithelioid carcinoma HeLa cells and endometrial adenocarcinoma Ishikawa cells. Further studies of these compounds revealed additional biological effects, including disruption of the cell membrane in high concentrations, cell cycle arrest in the S phase, and the induction of reactive oxygen species (ROS). Comparative analysis of the two classes of chiral organophosphorus derivatives of aziridines indicated that chiral phosphine oxides displayed significantly higher biological activity. Consequently, these findings suggest that chiral phosphine oxides may be potential candidates for the development of anticancer drugs. In light of the significant interest in preparations whose structure is based on a three-membered aziridine ring in terms of potential anticancer therapy, this research fits into the current research trend and should constitute a valuable addition to the current state of knowledge and the existing library of aziridine derivatives with anticancer properties.

Can MRI Accurately Diagnose and Stage Endometrial Adenocarcinoma?

Background and Objectives: Endometrial carcinoma is one of the most common gynecological cancers, and benign lesions such as endometrial hyperplasia, polyps, adenomyosis and leiomyomas should be included in the differential diagnosis. Magnetic resonance imaging has an important role in evaluating endometrial cancer and assessing the depth of myometrial invasion, and it closely correlates with the prognosis of the patient. The purpose of this study is to evaluate the MRI semiology of the endometrial carcinomas that mimic benign lesions, the main factors that may affect the correct diagnosis and the feasibility of magnetic resonance imaging to evaluate the depth of the myometrial invasion of endometrial cancer. Materials and Methods: This is a retrospective analysis of 45 patients that underwent MRI examinations and the lesions were pathologically diagnosed as endometrial carcinoma after surgical resection. This study evaluated the staging accuracy of T2-weighted imaging, diffusion-weighted imaging (DWI), ADC mapping and T1-weighted imaging with fat saturation before and after gadolinium injection. Results: In 36 of the 45 cases, the MRI of the lesion showed the characteristics of endometrial cancer and the diagnosis was certain. Nine lesions (20%) were described as unequivocal and had unspecific MR appearance. In eight of the nine cases (89%), the histopathologic report revealed the presence of leiomyomas and two of these cases (22%) were also associated with adenomyosis. The cause of underestimation in these patients was coexisting lesions exhibiting heterogenous intensity and contrast enhancement, which made it difficult to detect the margins of the lesions. The depth of the myometrial invasion was underestimated in nine cases and overestimated in three cases. The staging accuracy with MRI was 74%. There was a significant correlation between MR imaging and histopathologic finding in the assessment of myometrial invasion (p < 0.001). Cervical extension was noted in eight cases (18%), but was missed on MR imaging in two patients and overstaged in none. Six of them were associated with myometrial invasion in more than 50% of the thickness. There was a significant correlation between MR imaging and histopathologic finding in the assessment of cervical extension (p < 0.001). Conclusions: Our data confirm the high accuracy of MRI in the diagnosis and local staging of endometrial carcinoma. The information provided by MRI has an important role in planning the treatment and the prognosis of the patients.

Biomarkers in the Diagnosis of Endometrial Precancers. Molecular Characteristics, Candidate Immunohistochemical Markers, and Promising Results of Three-Marker Panel: Current Status and Future Directions.

Endometrial carcinoma stands as the most prevalent gynecological cancer and the fourth most common cancer affecting women. The incidence of endometrial cancer has been steadily increasing over the past decade, posing a significant threat to public health. The early detection of its precancers remains a critical and evolving concern to reduce mortality associated with endometrial carcinoma. In the last decade, our understanding of endometrial carcinoma and its precancers has advanced through systematic investigations into the molecular genetics of endometrial carcinoma and its precancers. In this review, we focus on advances in precancers associated with the endometrioid subtype, by far the most common histologic variant of endometrial adenocarcinoma. Recent investigations have led to the identification of new biomarkers, and the proposed incorporation of these biomarkers or biomarker panels into the diagnostic framework of endometrial carcinoma precancers. Here, we review these recent advances and their relevance to the histopathologic diagnosis of endometrial carcinoma precancers.

Abstract A021: Pilot study of daily exemestane in patients with Endometrial Intraepithelial Neoplasia (EIN) or grade 1 endometrial cancer

Abstract Introduction: The purpose of this study is to evaluate exemestane, an aromatase inhibitor, as a potential agent for the chemoprevention of endometrial cancer. Experimental procedures: This is a multi-center, phase IIA, single arm ‘window of opportunity’ pilot study of 25 mg per day of exemestane for 21-42 days in postmenopausal patients undergoing hysterectomy for endometrial intraepithelial neoplasia (EIN) or low-grade endometrial cancer. The primary objective is to determine if there is a decrease in proliferation index, measured by percent Ki-67 expression in endometrial tissue, from pre-treatment to post-exposure. Results of Ki-67 are compared with a historic control cohort of tumors from patients matched by preoperative histologic diagnosis, age, BMI category. Specimens from the historic control cohort included a preoperative endometrial biopsy as well as a surgical specimen, separated in time by less than 42 days. Secondary outcomes include comparison of Ki67 to historic controls, circulating serum estradiol and progesterone levels, pathologic response, tissue biomarkers, safety and adverse effects. Summary of Data: Forty patients accrued to the study between January of 2018 and March of 2021. The mean age was 63 (range 52-75). Thirty-nine patients (97.5%) self identifiedself-identified as white; 1 patient (2.5%) identified as Asian. The mean BMI was 40.3 (SD 9.75, range 22.8-60.5). Preoperative diagnoses included EIN, grade 1 endometrial adenocarcinoma, and grade 2 endometrial adenocarcinoma in 11 (27.5%), 26 (65%), and 3 (7.5%) patients respectively. Thirty-nine patients (97.5%) were compliant with exemestane dosing. All patients completed the study and no patients discontinued or interrupted therapy due to treatment related adverse events. Thirty-eight patients had evaluable specimens for both pre and post-treatment Ki-67 analysis. Median Ki-67 score decreased from 40.7% [IQR (33.9%, 50.3] at baseline to 18.1% [IQR (8.8%, 31.8%)]. This represents a median absolute change from baseline of -20.4% [IQR (-29.9, -6.7), p&amp;lt;0.001]. In total, percentage of Ki-67 in tumor cells declined in 31 patients and increased in 7 patients. In the historic control cohort, patients also had a decrease in Ki-67 score with a median absolute change from baseline of -6.7% [IQR (-12.7%, -1.3%), p&amp;lt;0.001]. However, the decrease in Ki-67 was greater in the study patients than the matched historic controls, with a median difference between the groups of -13.4% [IQR= (-23.3%, 6.9%), p=0.0095]. Serum estradiol levels did not change significantly between baseline and post-treatment (p=0.16). There was a small but significant increase from baseline to post-treatment in serum progesterone (0.14 ng/mL vs 0.37 ng/mL, p&amp;lt;0.001). Conclusion: In this pilot window of opportunity study, exemestane demonstrates anti-proliferative effects in endometrial intraepithelial neoplasia and low-grade endometrial cancer. This agent warrants further evaluation for the chemoprevention of endometrial cancer. Citation Format: Britt K. Erickson, Lisa Barrioullet, Rebecca C. Arend, Dina El-Rayes, Mahmoud Khalifa, Amy Skubitz, Kristin Boylan, Andrew Nelson, Bharat Thyagarajan, Thomas Havighurst, Richard Chappell, Eileen Dimond, Katina Deshong, Goli Samimi, Eva Szabo, Howard Bailey. Pilot study of daily exemestane in patients with Endometrial Intraepithelial Neoplasia (EIN) or grade 1 endometrial cancer [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr A021.

Endometrial Cancer in a Transgender Man with Prolonged Exogenous Testosterone Use.

Hormone therapy (HT) in transgender males requires monitoring. For amenorrheic transmasculine individuals on HT, episodes of abnormal vaginal bleeding should be assessed promptly. A 33-year-old transgender man on exogenous testosterone therapy for medical gender transition was found to have stage IV endometrioid endometrial adenocarcinoma. Surgical resection was performed for symptom control, and the patient was treated with palliative chemotherapy. The tumor was androgen receptor-negative, and, after a multidisciplinary discussion of the risks and benefits of continuing exogenous testosterone, testosterone therapy was restarted postoperatively. Long-term androgen use may have unknown implications for the development of malignancy, and treating reproductive organ cancer in transgender males may be complicated by the desire to continue androgen therapy.

Incidental findings during donor liver assessment: Single center experience

Intraoperative consultation of donor liver is an important part of transplant evaluation and determination of liver eligibility. In this study, we describe incidental pathologic findings discovered during the pretransplant evaluation of liver donors in our Institution from 1/2010 to 12/2022. During this 13-year period 369 intraoperative consultations from 262 liver donors were performed. Of those cases, incidental findings were identified in 22 cases (5.9 %) from 19 donors (7.3 %); two donors had more than one lesion. The median age of this subset of patients was 53 years (range: 18–70) and females predominated (63 %). Sixteen of the donors had abnormal findings in the liver: 6 bile duct hamartoma (BDH), 5 hyalinized nodule with Histoplasma capsulatum, 5 focal nodular hyperplasia (FNH), 2 bile duct adenomas (BDA), 1 biliary cyst and 1 hemangioma. One donor had both FNH and a BDH. One BDH and 1 BDA case was misdiagnosed as malignancy during the frozen section evaluation. Three donors had extrahepatic pathologies: a pancreatic tail schwannoma, a low-grade appendiceal mucinous neoplasm, and a lymph node with metastatic endometrial endometrioid adenocarcinoma. Of the 19 livers, the final organ disposition was available for 9: 6 were transplanted (67 %) and 3 were discarded (33 %). Two of the 3 discarded organs were misdiagnosed BDH and BDA cases, and one was incorrectly reported as having 90 % microvesicular steatosis during the frozen assessment. We present the clinicopathologic characteristics of liver donors with incidental findings during the pre-transplant evaluation which could lead to unwarranted graft dismissal if misdiagnosed. Additionally, incidental fungal infections can have implications for immunosuppressive therapy and the decision to use or reject the graft.

Pathogenetic characteristics of endometrioid adenocarcinoma of uterus at present stage

Endometrial cancer (EC) is one of the most common cancers with a constantly and steadily growing incidence worldwide. The main reason for EC development, in addition to the female population aging, involves the obesity epidemic and associated hyperinsulinemia. Screening for EC has not been developed. However, endometrial carcinoma (ECa) demonstrates a specific symptomatology and clinical picture, and diagnostic methods are available, sensitive and defined by a certain range of comorbid diseases. These factors allow early ECa diagnosis in 80 %. The methods of treatment are standardized, depending on the stage of RTM and the morphological structure of EC, the age of the patient and allow to achieve 72–76 % of the overall 5-year survival rate. The methods of treatment are standardized, depending on the EC stage, the morphological structure of ECa, and the patient’s age, and allow achieving the 5-year overall survival of 72–76 %. The disease promised a favorable outcome and seemed to be controlled. However, at the end of the last century, researchers started to report the clinical and morphological heterogeneity of ECa, which allowed Ya. V. Bohman to propose a dichotomous division of EC into clinical and pathological variants. Such a division was accepted all over the world and required re-evaluation of the prognostic value of various endometrial adenocarcinoma histotypes depending on the phenotype and hormonogenesis of ECa. Initially, adenosquamous cancer (or endometrioid adenocarcinoma with squamous metaplasia, in the modern classification) was also classified as estrogen-dependent endometrioid adenocarcinoma, and squamous cell endometrial cancer was classified as an unfavorable type with a poor prognosis and without hormonal influence. Interest in the squamous cell component in dimorphic endometrial adenocarcinoma has repeatedly arisen over the past decades due to its unpredictable clinical course. The newest TCGA molecular classification of EC did not clarify the issues, but gave rise to new ones related to the etiology and carcinogenesis of this ECa histotype and its clinical interpretation.

Expressions of HuR, Methyl-HuR and Phospho-HuR in Endometrial Endometrioid Adenocarcinoma Are Associated with Clinical Features.

HuR regulates cytoplasmic mRNA stability and translatability, with its expression correlating with adverse outcomes in various cancers. This study aimed to assess the prognostic value and pro-oncogenic properties of HuR and its post-translational isoforms methyl-HuR and phospho-HuR in endometrial adenocarcinoma. Examining 89 endometrioid adenocarcinomas, we analyzed the relationship between HuR nuclear or cytoplasmic immunostaining, tumor-cell proliferation, and patient survival. HuR cytoplasmic expression was significantly increased in grade 3 vs. grade 1 adenocarcinomas (p < 0.001), correlating with worse overall survival (OS) (p = 0.02). Methyl-HuR cytoplasmic expression significantly decreased in grade 3 vs. grade 1 adenocarcinomas (p < 0.001) and correlated with better OS (p = 0.002). Phospho-HuR nuclear expression significantly decreased in grade 3 vs. grade 1 adenocarcinomas (p < 0.001) and non-significantly correlated with increased OS (p = 0.06). Cytoplasmic HuR expression strongly correlated with proliferation markers MCM6 (rho = 0.59 and p < 0.001) and Ki67 (rho = 0.49 and p < 0.001). Conversely, these latter inversely correlated with cytoplasmic methyl-HuR and nuclear phospho-HuR. Cytoplasmic HuR expression is a poor prognosis marker in endometrioid endometrial adenocarcinoma, while cytoplasmic methyl-HuR and nuclear phosphoHuR expressions are markers of better prognosis. This study highlights HuR as a promising potential therapeutic target, especially in treatment-resistant tumors, though further research is needed to understand the mechanisms regulating HuR subcellular localization and post-translational modifications.

Endometrial Serous Adenocarcinoma and Perineal Leiomyosarcoma: A rare case report of Synchronous Primaries

The simultaneous presentation of endometrial carcinoma and perineal leiomyosarcoma in a patient as a synchronous tumor is very rare.

The diagnostic and prognostic significance of L1 cell adhesion molecule, Sperm-associated antigen 9 and P53 expression in endometrial lesions (immunohistochemical study)

Background Endometrial carcinoma is the most common invasive neoplasm of the female reproductive tract. L1 cell adhesion molecule (L1CAM), Sperm-associated antigen 9 (SPAG9), and P53 have a role in the process of tumorigenesis and progression of several human malignant tumors, however, the role of them in cancer of endometrium is still not clear. Aim The study was performed to evaluate L1CAM, SPAG9, and P53 expression about different clinicopathological parameters in endometrial endometrioid adenocarcinoma. Methods The immunohistochemical study was performed on 50 cases of endometrial lesions including endometrial hyperplasia without atypia (10 cases), endometrial hyperplasia with atypia (10 cases), and endometrial endometrioid carcinoma (30 cases). Immunohistochemical staining techniques were used to evaluate the role of L1CAM, P53, and SPAG9 in endometrial endometrioid adenocarcinoma (EEC) and their relation to different clinicopathological data and patient’s survival followed for 36 months. Results This study declared that both L1CAM and SPAG9 were found to be upregulated in EEC. Their over-expression was related to adverse clinicopathological parameters including high tumor grade, deep myometrial invasion, lymphovascular Invasion (LVI), and advanced tumor stage, while there was no significant relation between their expression and tumor size, cervical affection, and lymph node involvement. A high statistically significant link between L1CAM expression and poor patient survival was detected. Mutant type P53 was significantly related to adverse clinicopathological data as high tumor grade, deep myometrial invasion, lymphovascular space invasion (LVSI), and high tumor stage. There was a positive significant relation between mutant type P53 and high SPAG9. Conclusions The early identification of EEC in asymptomatic high-risk women may benefit from L1CAM and SPAG9 testing in combination with P53 protein. Also, they could be viewed as separate predictive variables in the EEC and might play a crucial part in the EEC’s chemoresistance.

Survival outcomes of neoadjuvant therapy for the treatment of stage IVB endometrial adenocarcinoma

Survival outcomes of neoadjuvant therapy for the treatment of stage IVB endometrial adenocarcinoma

Long-term follow-up of a patient with disseminated endometrial adenocarcinoma and cerebral metastases

Long-term follow-up of a patient with disseminated endometrial adenocarcinoma and cerebral metastases

Prognostic factors and survival of women with endometrial carcinoma attending a tertiary care center in South India

Background: Endometrial cancer is the most common malignancy of the female genital tract in developed countries and the 4th most common cancer in women after breast, lung, and colorectum. It has an estimated lifetime risk of 2.6% for women living in developed nations, and a median age at diagnosis of 61 years. The majority of women with endometrial carcinoma are diagnosed at an early stage and may be cured by surgery with or without radiotherapy. When detected early it has an average survival rate of 95%. There are various prognostic factors epidemiological, tumor characteristics, and the treatment undertaken that have a significant influence on the disease-free survival (DFS) and overall survival (OS) of the disease. Here an attempt was made to analyze the prognostic factors and to determine the DFS among women diagnosed to have endometrial cancer. Aims and Objectives: The aim of this study was to evaluate the factors determining the prognosis and survival of women with endometrial cancer. Materials and Methods: A retrospective review was conducted on 82 cases diagnosed as endometrial carcinoma registered in the Department of Obstetrics and gynecology department in a government hospital. They were subsequently followed up over a period of 42 months. Results: The recurrence-free survival rate was found to be 90.2%. The estimated mean survival time using the inverse Kaplan–Meir method was 37.5 months (95% CI 34.6–41.34) for recurrence-free survival and 38.24 months (95% CI 34.77–41.72) for OS. Endometroid adenocarcinoma was the most common histological variant (79.3%). Diagnosis at an early stage (FIGO Stage 1 and 2) was more (74.3%) as compared to advanced stages. The calculated recurrence rate was 9.5% with a tumor-related mortality of 32.9%. The most common site of recurrence was the vault (62.5%). The statistically significant variables affecting the recurrence rates were the histological type of tumor and the grade. Prognostic variables with statistically significant influence on recurrence-free survival and OS were age, stage of the tumor, grade of the tumor, type of surgical procedure underwent by the patient, and the use of adjuvant therapy. Conclusion: The present study was able to demonstrate that endometrial adenocarcinoma diagnosed at an early stage has a very good prognosis and survival rates in Kerala. FIGO stage and grade of the tumor being the most important variables determining DFS and OS.

Complete Remission of Multiple Pulmonary Metastases of Endometrial Adenocarcinoma Treated with a Mixture of Low Molecular Weight Fucoidan and Canvaria gladiata Extract: A Case Report

Endometrial cancer (EC) is the most common malignant tumor in post-menopausal women, and the lung is one of the organs to which endometrial adenocarcinoma metastasizes. Chemotherapy is helpful for various malignancies, but not all are successful. A 71-year-old-Japanese-woman was diagnosed with metastatic lung cancer stage IV of primary endometrial adenocarcinoma. She received chemotherapy and hormone therapy after a total hysterectomy and pelvic lymphadenectomy. Subsequently, she visited this clinic for a second opinion as the metastatic lung cancer had repeated remissions and recurrences. Here, the authors report a case in which complete remission of metastatic lung cancer was achieved by using a product containing low molecular weight fucoidan extract (LMF) and Canavalia gladiata extract (CG) (LMF-CG) in combination with Medroxyprogesterone acetate (MPA) hormone therapy.

Efficacy of ABCA1 Transporter Proteins in Patients with Endometrial Cancer: an In Vitro Study.

Endometrial carcinoma (EC) is a typical gynecological malignant tumor that occurs more frequently every year. Obesity is a significant contributor to the development of EC and its prognosis. Lipid metabolism and malignant tumors have a long history of association. Elevated cholesterol levels are made possible by adenosine triphosphate-binding cassette protein A1 (ABCA1) deficiency, which eventually promotes cancer cell survival. The aim of this study was to examine at the ABCA1 gene expression levels in EC patients. The relationship between ABCA1 and the occurrence, progression, and prognosis of EC is discussed in this article as a potential mechanism. The samples of 45 endometrial adenocarcinoma patients were retrospectively included in this study and they were further divided into Grade 1 (15), Grade 2 (15), Grade 3 (15) tumors, control group. Twenty-nine endometrial tissues without a confirmed diagnosis of endometrial cancer made up the control group. ABCA1 gene expression was examined using real-time polymerase chain reaction. According to the results, the gene expressions of the patient group were higher than the control group When each Grade was compared with the control group, statistically significant results were obtained. After analyzing the data, it was found that the patient group was generally higher than the control group (p < 0.05) and there were differences in the grades of the patient group (p < 0.05). When the ABCA1 expressions of the grade groups and control groups were compared separately, a difference was found between Grade 1, Grade 2 and Grade 3 and the control group (p= 0.0001). According to the findings of our study, a key component in the growth of EC tumors is the increase in cholesterol production caused by a reduction in ABCA1.

Surface-enhanced Raman spectroscopy in women with benign and malignant endometrial diseases

Background. This study aimed to enhance early detection of endometrial cancer in women and distinguish benign conditions from endometrial cancer using surface-enhanced Raman scattering (SERS) analysis of blood plasma, thus increasing diagnostic efficacy.&#x0D; Materials and methods. The study of blood plasma from 95 female patients aged 22–79 years was performed. The patients were divided into four groups: group 1 included 29 women with endometrial adenocarcinoma, group 2 included 31 patients with endometrial polyp, group 3 included 10 women with endometrial hyperplasia, and the comparison group consisted of 25 healthy women. Blood plasma was analyzed via SERS, with three Raman spectra recorded per sample. Spectral measurements of the SERS substrate were assessed using dried samples on an experimental bench equipped with the spectrometric system RL785 (LLC “Foton-Bio”, Russia), incorporating a CCD detector, laser radiation source with a wavelength of 785 nm, and ADF U300 microscope (ADF, China). A silver substrate composed of dried silver colloid was used to demonstrate the enhancement effect on the Raman signal from the surface of the blood plasma.&#x0D; Results. Spectral and specific features that distinguish adenocarcinoma, polyps, and endometrial hyperplasia were identified and evaluated. Spectral and quantitative differences specific to each condition, which are crucial for the differential diagnosis of pathologic tissues, were also identified. The accuracy rates of the optical diagnostics in distinguishing endometrial adenocarcinoma from the control group and endometrial hyperplasia were 87% and 85%, respectively, for the calibration and verification spectral sets (where the sensitivity and specificity were 66% and 92% for the spectral verification set, respectively). The accuracy rates of distinguishing control from endometrial hyperplasia and endometrial adenocarcinoma were 86% and 85%, respectively, and the accuracy of distinguishing endometrial hyperplasia from control and endometrial adenocarcinoma was 81% for the calibration and verification sets of spectra. In addition, the study demonstrated improved accuracy in differentiating adenocarcinoma from hyperplasia, including polyps. The accuracy rate was 93% in the calibration set of spectra, with sensitivity and specificity of 96% and 90%, whereas in the validation set, it was 91%, with sensitivity and specificity of 93% and 88%, respectively.&#x0D; Conclusions. The study demonstrated the potential use of SERS for differentiating expression patterns in endometrial cancer from those in benign conditions.

Obesity is associated with improved progression-free survival in Microsatellite-Instability-High endometrial cancer treated with pembrolizumab

ObjectivesTo determine the clinical predictors of response rate, progression-free survival (PFS), and overall survival (OS) to pembrolizumab in advanced or recurrent, mismatch repair deficient (MMRd) or Microsatellite Instability-High (MSI-H) endometrial adenocarcinomas. MethodsA retrospective, single institution study was conducted among women with recurrent or advanced MMRd or MSI-H endometrial adenocarcinomas treated with single-agent pembrolizumab at our institution from 2017 to 2021. Logistic regression was used for univariable and multivariable analyses. PFS and OS were estimated using the methods of Kaplan and Meier and modeled via Cox proportional hazards regression. Log-rank test was used for intergroup comparisons based on body mass index (BMI). ResultsAmong the 44 patients included in the analysis, the median BMI was 32.9 (range 18.5–51.8). Median cycles of pembrolizumab given was 11.5 (range 2–37). Median follow-up was 33 months (range 5–61) with a response rate of 63.6% and stable disease rate of 75%. When stratified by obesity status (BMI≥30), disease control rate was 59.8% in patients with a BMI < 30 and 85.2% in patients with a BMI≥30 patients (p = 0.05). On multivariable analysis, obesity was associated with increased rate of disease control (OR 4.03, 95%CI 1.09, 28) while prior smoking was associated with decreased rate of disease control (OR 0.18, 95%CI 0.03, 0.85). PFS was significantly increased among patients with a BMI≥30 (p = 0.03) but OS was similar (p = 0.5). ConclusionIn this retrospective study, obesity is associated with increased rates of disease control and improved PFS in patients treated with pembrolizumab for recurrent or advanced MMRd/MSI-H endometrial adenocarcinomas.

Two lncRNA signatures with cuproptosis as a novel prognostic model and clinicopathological value for endometrioid endometrial adenocarcinoma.

Cuproptosis may contribute to tumorigenesis. However, the predictive value and therapeutic significance of cuproptosis-related lncRNAs (CRLs) in endometrioid endometrial adenocarcinoma (EEA) remains unknown. We obtained RNA-seq data from TCGA database and searched the Literature to identify cuproptosis-related genes. Using machine learning models, we identified prognostic lncRNAs for cuproptosis. Immune properties and drug sensitivity were investigated based on these signatures. Further, a ceRNA network was constructed by bioinformatics and in vitro experiments were performed. We determined two cuproptosis-related signatures to build the prognostic model in EEA. Afterward, the risk scores of two cuproptosis-related signatures were associated with clinicopathological molecular typing and as independent prognostic factors for EEA. In addition, we observed significant differences in immune function, checkpoints, and CD8+ T lymphocyte infiltration between the two risk groups. Furthermore, chemotherapy drugs such as AKT inhibitors exhibited lower IC50 values in the high-risk group. We speculate that ACOXL-AS1 can be served as an endogenous 'sponge' to regulate the expression of MTF1 by miR-421. Through in vitro experiments, we preliminarily validated the ceRNA network relationship in the cellular model. In EEAs, this study proposed a broad molecular signature of CRLs are promising biomarkers for predicting clinical outcomes and therapeutic responses.

The pregnancy and oncology outcome of fertility-sparing management for synchronous primary neoplasm of endometrium and ovary

PurposeTo investigate the efficacy of fertility-preserving treatment for young women with synchronous primary neoplasm of endometrium and ovary.MethodsWe retrospectively reviewed eight patients with concurrent primary grade 1 presumed stage IA endometrioid endometrial adenocarcinoma (EEA) or endometrial atypical hyperplasia (EAH) and primary stage I ovarian tumors who underwent fertility-sparing treatment in the Obstetrics and Gynecology Hospital of Fudan University between April 2016 and December 2022.ResultsSynchronous endometrial and ovarian cancers (SEOC) accounted for 50% of these eight patients. The median age of patients was 30.5 years (range, 28–34 years). None of them received chemotherapy. The median treatment time was 4 months (range, 3–8 months). 87.5% (7/8) cases achieved complete response (CR), and the median time to CR was 3.8 months (range, 1.5–7.7 months). Among patients who got CR, none of them showed any signs of recurrence. Pregnancies and successful deliveries were achieved in 4 of 5 patients. Till September 2023, the median follow-up period was 50.5 months (range:15.2–85.2 months).ConclusionFertility-sparing treatment is feasible for highly selected patients with synchronous neoplasm of the endometrium and ovary, but strict screening and monitoring are mandatory. Though the results of our limited cases are encouraging, long follow-up and more clinical data are required. Enrolled patients must be fully informed of the risks during conservative treatment.