Classification Of Endometrial Cancer Research Articles

Molecular classification of endometrial cancers (EC) and association with relapse-free survival (RFS) and overall survival (OS) outcomes: Ancillary analysis of GOG-0258.

Determine if molecular classification using mismatch repair (MMR) and p53 protein expression predicts recurrence-free survival (RFS) and overall survival (OS) in endometrial cancer (EC) patients treated with chemotherapy and radiation (CRT) versus chemotherapy (CT). GOG-0258, a phase III randomized trial (NCT00942357), compared CRT to CT. Immunohistochemistry assessed MMR and p53 status. Kaplan-Meier curves and adjusted Cox models analyzed survival outcomes by molecular subtype. ECs classified as deficient MMR (dMMR) (27%), p53 abnormal (p53abn) (24%), and p53 wild type (p53wt) (49%). p53abn were more frequent in patients that were older, Black, and had serous histology (p<0.001). Median follow up was 113months. Five-year RFS and OS were worse with p53abn (29% [Hazard Ratio (HR)=3.39 (95% Confidence Interval (CI): 2.34-4.91)] and 39% [HR=4.64 (95% CI: 3.16-6.79)] compared to those with p53wt (referent) (p<0.001). The five-year RFS and OS for dMMR cancers were (58% [HR=1.30 (95% CI: 0.85-1.97)] and 77% [HR=1.53 (95% CI: 0.99-2.36)] compared to those with p53wt (69% and 85%). After adjusting for age, gross residual disease, and treatment, p53wt improved RFS with CRT compared to CT in an exploratory analysis (77% vs 60%; HR=0.54 (95% CI: 0.32-0.94). The 5-year and 10-year OS rates were similar in CRT compared to CT in all subgroups. Molecular classification appears to be predictive and prognostic, with worse survival in those with p53abn tumors. In an exploratory analysis, p53wt appears to predict improved RFS, favoring CRT over CT. There was no difference in treatment efficacy based on molecular subtype for OS.

Molecular Genetic Classification of Endometrial Cancer as a New Tool for Selecting the Scope of Surgical Treatment

Введение. Предложенная FIGO в 2023 г. новая система стадирования рака эндометрия ориентирована на включение молекулярно-генетической классификации. В настоящее время все еще актуальным является вопрос определения объема хирургического вмешательства с учетом молекулярно-генетического подтипа опухоли. Материалы и методы. Исследование проведено в ГКБ им. С.П. Боткина ДЗМ в 2023 г. в период с июня по декабрь. В группу наблюдения, состоящую из 50 пациенток, были включены больные с гистологически верифицированным РЭ 1 клинической стадии различной степени злокачественности, эндометриоидного типа, которым на дооперационном этапе было выполнено иммуногистохимическое исследование на наличие p53abn и MMRd. Все пациентки были разделены на 3 подгруппы: пациентки с опухолями MMRd+, с опухолями p53abn+ и с негативными в отношении MMRd и p53abn исследованиями. Объемы лапароскопических оперативных вмешательств включали экстирпацию матки с придатками, экстирпацию матки с придатками и биопсию сторожевых лимфатических узлов с ICG картированием, при неудачном окрашивании индоцианином в группах промежуточного и высокого риска производилась тазовая лимфаденэктомия с соответствующей стороны, экстирпация матки с придатками и тазовая лимфаденэктомия, экстирпация матки с придатками, тазовая и поясничная лимфаденэктомия. Для распределения пациентов по стадиям использовались классификации TNM 8 пересмотра 2017 г. и FIGO 2009 и 2023 гг. После получения результатов гистологического исследования был проведен анализ корреляции поражения лимфатических узлов с учетом стадии заболевания по FIGO 2009 и FIGO 2023 и молекулярно-генетического подтипа опухоли. Результаты. Частота встречаемости пациенток с MMRd/p53abn негативным подтипом составила 74 %, пациентки с мутантным профилем экспрессии p53abn — 8 %, MMRd был выявлен в 18 % случаев. При молекулярно-генетическом подтипе MMRd частота лимфогенного метастазирования увеличилась до 22,2 %, а при p53abn составила уже 25 %. Выводы. В настоящее время недостаточно данных для формулирования новых хирургических подходов на основании молекулярной классификации. Тем не менее, представляется целесообразным увеличивать объем хирургического вмешательства у пациенток с p53abn, а пациенткам с MMRd обязательно выполнять хирургическое стадирование лимфатических узлов.

Molecular subtype of ovarian clear cell carcinoma: an analysis of 80 Chinese patients using the TCGA molecular classification of endometrial cancer

Molecular subtype of ovarian clear cell carcinoma: an analysis of 80 Chinese patients using the TCGA molecular classification of endometrial cancer

Analysis of Differences in the Classification of Endometrial Cancer Patients in Poland.

Background: Endometrial cancer (EC) incidence and mortality have been steadily rising globally over recent decades. The introduction of advanced molecular technologies, such as next-generation sequencing (NGS) alongside the FIGO 2023 classification, presents opportunities for refined diagnostics and risk stratification. This study aimed to analyze differences in EC classification among oncology centers in southeastern Poland. Methods: Data were collected from 461 consecutive patients newly diagnosed with EC between 2022 and 2024 at four major oncology centers in southeastern Poland. Molecular and immunohistochemical (IHC) analyses were conducted on formalin-fixed paraffin-embedded (FFPE) tissues to identify key markers, including POLE mutations, MSI-H, and p53 status. Results: The application of the FIGO 2023 staging system revealed statistically significant inter-center differences, with Centers 1 and 4 diagnosing a higher proportion of early-stage cases. The most prevalent subtype was NSMP, observed in 51% of cases. MSI-H occurred in 13-36% of patients, depending on the center. p53 mutations ranged from 9% to 26%. POLE mutations were identified in 4% of patients overall. Significant variations in the molecular subtype distribution across centers highlight potential differences in diagnostic access or tumor biology. Conclusions: The findings demonstrate regional differences in EC staging and molecular profiles in Poland, potentially reflecting disparities in diagnostic resources, methodologies, or tumor characteristics. Addressing these variations through standardized diagnostic protocols and equitable access to molecular tools is critical for optimizing patient outcomes. Future research should focus on evaluating the impact of molecular markers on therapy response and prognosis to guide personalized treatment strategies.

A Transformer-based Semantic-Aware U-Net Model for Improving in Endometrial Cancer Detection

The rise in Endometrial Cancer (EC) necessitates early diagnosis using medical imaging. Deep learning models have been developed to address misdiagnosis, but their accuracy is limited by small-scale datasets. To address this issue, a new Deep EC Prediction (DeepECP) model, combining Feature Entanglement Generative Adversarial Network (FE-GAN) and multimodal Convolutional Neural Network with Long Short-Term Memory (CNN-LSTM), has been designed to generate synthetic MRI images and detect EC stages. However, precise identification and categorization of various EC stages require the segmentation of MRI scans. While the U-Net model is frequently used for this task, it has constraints in capturing long-range relationships. Other models, like Transformers with self-attention mechanisms may not have strong low-level localization capabilities. Hence, this paper introduces a Transformer-based Semantic-Aware U-Net (TSA-UNet) model with DeepECP for segmenting and classifying EC stages in MRI scans. The TSA-UNet model combines Transformer and U-Net structures, consisting of encoder, fusion, and decoder units. The encoder is a CNN-Transformer that captures multilevel bitemporal features and encodes tokenized sequences to get high-level features. The Transformer unit uses Semantic Guidance Attention (SGA) to enhance feature discrimination and reduce semantic gaps. An Adaptive Cross-Fusion (ACF) unit merges bitemporal features, and a Cascaded Upsampling Decoder (CUD) combines low-level CNN and high-level Transformer characteristics to localize and segment EC stages in MRI scans. The segmented images are then inputted to the DeepECP model for classification. Finally, the experimental outcomes reveal that the TSA-UNet-DeepECP attains higher efficiency than conventional models for segmentation and classification of EC from MRI images.

Molecular Classification of Endometrial Cancers Using an Integrative DNA Sequencing Panel.

Adoption of molecular classification in endometrial cancer (EC) into clinical practice remains challenging due to complexity in coordination of multiple assays. We aimed to develop a simple molecular technique to classify ECs into four subgroups using our custom-designed targeted sequencing panel. Patients with newly diagnosed ECs were prospectively recruited from three cancer centres in Ontario, Canada. Using our panel, 181 ECs were sequenced. Variants were analysed for pathogenicity and clinicopathologic information was collected through medical records retrospectively. Of 181, 86 (48%) were mismatch repair deficient (MMRd), of which 62 (72%) harboured MLH1 promoter methylation and 24 (28%) had pathogenic variants in MMR genes. Of single classifiers, three (1.8%) had pathogenic POLE (POLEmut), 15 (9%) had TP53 mutations (p53abn) and 61 (37%) had no specific molecular profile subtype (NSMP). Sixteen (9%) had more than one molecular classifying feature, with eight (4%) MMRd-p53abn, six (3%) POLEmut-MMRd, one (0.5%) POLEmut-MMRd-p53abn and one (0.5%) POLEmut-p53abn. When MMRd group was further subclassified according to mechanism of MMR loss, MLH1 promoter methylated group had worse outcomes than those with somatic MMR pathogenic variants. Our panel can classify ECs into four subgroups through a simplified process and can be implemented reflexively in clinical practice.

Molecular classification of endometrial cancer in a Brazilian cohort

Molecular classification of endometrial cancer in a Brazilian cohort

Loss of vimentin expression in preoperative biopsies independently predicts poor prognosis, lymph node metastasis and recurrence in endometrial cancer

BackgroundPrecise preoperative risk classification of endometrial cancer is crucial for treatment decisions. Existing clinical markers often fail to accurately predict lymph node metastasis and recurrence risk. Loss of vimentin expression has emerged as a potential marker for predicting recurrence in low-risk endometrial cancer patients. We assessed whether vimentin expression in preoperative biopsies predicts poor prognosis and lymph node metastasis in a large multicentre cohort.MethodsVimentin expression was evaluated using immunohistochemistry in 1483 patients diagnosed with endometrial cancer across 14 hospitals in Europe. Expression levels of vimentin were analyzed in conjunction with clinical characteristics for predicting disease-specific survival and lymph node metastases.ResultsVimentin loss was significantly associated with aggressive disease and poor survival. Adjusted for clinicopathological variables, vimentin remained independently prognostic with a hazard ratio (HR) of 1.68 (95% CI 1.16–2.42, P = 0.006). Vimentin expression remained independently prognostic in endometrioid endometrial cancer- and FIGO staged 1 patient. Interestingly, vimentin loss independently predicted lymph node metastases, with an HR of 1.83 (95% CI 1.13–2.95, P = 0.014).ConclusionsLoss of vimentin in preoperative biopsies serves as an independent predictor of poor prognosis and lymph node metastases. Incorporating vimentin as a clinical marker can improve risk stratification and treatment decisions.

Challenges in implementation of molecular classification in early stage endometrial cancer-An NRG Oncology cooperative group mixed-methods study.

Professional guidelines recommend molecular profiling for mismatch repair (MMR), p53, and polymerase epsilon (POLE) status in endometrial cancer (EC). However, adoption in the United States has not been documented, and barriers to the implementation of testing have not been described. In this mixed-methods study, implementation science frameworks were used to develop a quantitative survey. Gynecologic oncologists, medical oncologists, radiation oncologists, and pathologists affiliated with NRG Oncology programs were contacted through snowball sampling and were surveyed during 2022-2023. A subset of respondents was interviewed. Statistical and thematic analyses were performed. At least 403 NRG Oncology-affiliated providers were contacted for the survey, and 107 (26.6%) responded. Greater than 90% of respondents perceived POLE, MMR, and p53 status as important for clinical care. MMR and p53 tests were perceived as easy to obtain, but only 24.2% of respondents reported that POLE testing was moderately or very easy to obtain. Respondents from academic sites reported better access to molecular classification and perceived greater importance of molecular classification compared with respondents from community sites. In thematic analysis of 13 qualitative interviews, cost concerns were reported as large barriers to testing. Interviewees reported a desire for prospective data to guide treatment selection based on classification results. Although integrating molecular classification into standard pathologic reporting is recommended, and clinicians perceive molecular profiling in early stage EC as important, survey respondents noted significant implementation barriers. Implementation challenges that differ between community oncology and academic practice settings were identified. Strategies to improve equitable access to molecular classification of early stage EC are needed.

NCLN as a potential prognosis biomarker in endometrial cancer

Endometrial cancer (ECs) stands as one of the three major malignancies impacting females globally, with its incidence steadily increasing. ECs can be categorized into two types based on their clinicopathological features. Type I ECs typically exhibit low stage, favorable histological types, and low histological grade, correlating with a more favorable prognosis. Conversely, Type II ECs present with advanced-stage disease, aggressive behavior, and poorer histological types, resulting in a worse prognosis.The expression level of progesterone receptors (PR) holds significant importance in determining the prognosis of patients with ECs. Elevated levels of PR are linked to a more favorable prognosis, primarily attributed to progesterone's inhibitory influence on cancer cell proliferation and invasion. Moreover, progesterone promotes cell cycle inhibition through its regulation of PR, further contributing to improved outcomes in ECs.Nicalin (NCLN) plays a crucial role in facilitating the translocation of multichannel membrane proteins to the endoplasmic reticulum membrane and is implicated in embryonic development. Structurally akin to NODAL Modulator (NOMO), NCLN antagonizes NOMO during embryogenesis, forming a complex that antagonizes the Nodal pathway, thereby influencing mesoderm development. However, the precise relationship between NCLN and ECs remains incompletely understood.Our research findings reveal that NCLN actively stimulates the proliferation of ECs cells and exhibits a positive correlation with PR, albeit without impacting ER. Moreover, the expression levels of NCLN in ECs demonstrate associations with distinct histological types. These observations suggest that NCLN could emerge as a promising marker in the histological classification of ECs.

Translating biological insights into improved management of endometrial cancer.

Endometrial cancer (EC) is the most common gynaecological cancer among women in high-income countries, with both incidence and mortality continuing to increase. The complexity of the management of patients with EC has evolved with greater comprehension of the underlying biology and heterogeneity of this disease. With a growing number of novel therapeutic agents available, emerging treatment regimens seem to have the potential to helpto address the concerning trends in EC-related mortality. In this Review, we describe the epidemiology, histopathology and molecular classification of EC as well as the role of the new (2023) International Federation of Gynecologists and Obstetricians (FIGO) staging model. Furthermore, we provide an overview of disease management in the first-line and recurrent disease settings. With increasing use of molecular profiling and updates in treatment paradigms, we also summarize new developments in this rapidly changing treatment landscape.

Universal screening for Lynch syndrome in endometrial cancer diagnoses in Auckland, New Zealand: The initial experience.

Universal mismatch repair immunohistochemistry (MMR IHC) tumour testing in endometrial cancer (EC) for Lynch syndrome (LS) was introduced in Auckland, New Zealand, in January 2017. Identifying patients with LS allows them and their families to access risk reduction strategies. Universal MMR IHC testing aids in the molecular classification of EC and has prognostic and therapeutic implications. We aimed to determine the incidence of LS in women with EC in Auckland, New Zealand, following the introduction of MMR testing and the impact of universal screening on local genetic services. This is a retrospective clinicopathological evaluation of women with a new EC diagnosis referred to the Auckland Gynaecological Oncology Unit from 1/1/17 to 31/12/18. Patient data were extracted from the Gynaecological Oncology Unit database and electronic records, and analysed using descriptive statistics. During the study period, 409 patients were diagnosed with EC, with an over-representation of Pacific Islanders (32.5%). Of these, 82.6% underwent MMR IHC testing, 20% were MMR-deficient (MMRd), and 71% had somatic hypermethylation. The Pacific Islander population had a 64% (odds ratio 0.36, P = 0.005) reduction in the odds of having MMRd tumours compared with Europeans. Of the patients who underwent MMR IHC testing, 5.5% were referred to a genetic clinic for germline testing. LS was confirmed in eight patients (2.3%). LS was diagnosed in 2.3% of patients. There was an over-representation of Pacific Islanders in the EC group but not among those diagnosed with LS.

Colombian consensus for the molecular diagnosis of endometrial cancer

Objective: The Cancer Genome Atlas research program (TCGA) developed the molecular classification for endometrial cancer with prognostic and therapeutic utility, which was replaced by the ProMisE (Proactive Molecular Risk Classifier for Endometrial Cancer) classification by consensus and international guidelines due to its high cost. This article aims to present national recommendations from an expert consensus that allows unification and implementation of the molecular classification for women with endometrial cancer nationwide, with a rational use of resources and technology. Methods: Consensus of 36 experts in clinical oncology, oncological gynecology, pathology, and genetics, with clinical practice in the national territory. The leader group performed a literature review and structuring of questions rated 1 to 9 points. A modified nominal group technique was used. There was a face-to-face meeting with master presentations, deliberative dialogue, and Google Forms (Google LLC, Mountain View, CA, USA) questionnaire voting with analysis and discussion of responses. The non-consensual responses led to a second round of voting. The final manuscript was finally prepared and revised. Results: Seven recommendations were formulated integrating the panelist responses based on evidence, but adjusted to the Colombian context and reality. Recommendation 1. The molecular classification is recommended in all the endometrial cancers using the immunohistochemistry markers as subrogated results from the molecular profile initially proposed in the TCGA classification. Recommendation 2. The sequential test strategy is recommended, starting with the immunohistochemistry markers (p53, MLH1, MSH 2, MSH6, PMS2) simultaneously in all the patients, defining to request POLE (DNA polymerase epsilon) (if available) according to the risk classification based on the surgical piece. Recommendation 3. It is recommended, that the gynecologist oncologist should be the one to request the POLE (if available) according to the final pathology report. This test must be requested for all endometrial cancers stage I-II, except in low risk (stage IA low grade endometrioid histology without linfovascular invasion normal p53) and, stages III-IV without residual disease, without affecting the request of subrogated immunohistochemistry molecular markers upon histology. The consensus proposes that the POLE is requested after the immunohistochemistry and according to the categories in the risk classification established by the 2020 ESGO/ESTRO/ESP guidelines. Recommendation 4. It is recommended to perform immunohistochemistry for hormonal receptors for all women with endometrial cancer and the HER2 in patients with p53abn, simultaneously with the others immunohistochemistry markers. Recommendation 5. It is recommended to perform the immunohistochemistry markers (p53, MLH1, MSH2, MSH6 y PMS2) in an initial endometrial biopsy or curettage when the specimen is adequate and available. In case the initial immunohistochemistry is inconclusive, or there are histological discrepancies between the initial and definitive pathology, it is recommended to repeat the molecular profile in the surgical pathology. The immunohistochemistry markers must be reported in the pathology report according to the CAP (College of American Pathologists) recommendations, independently of the type of sample. Recommendation 6. It is recommended to perform MLH1 promoter methylation testing in patients who exhibit loss of expression of MLH1 in immunohistochemistry whether it is accompanied or not with loss of expression of PMS2. All the patients with deficient MMR (mismatch repair), should be sent for genetic counseling to rule out Lynch syndrome. Recommendation 7. It is recommended to consider the molecular classification in addition to the classical histopathological criteria when making adjuvant judgments, as incorporated by the classification of prognostic groups of the 2020 ESGO/ESTRO/ESP guidelines. Conclusions: It is necessary to implement the molecular classification of endometrial cancer in clinical practice in accordance to the Colombian context, due to its prognostic and probably predictive value. This will enable the characterization of the Colombian population in order to offer individualized guided treatments. This is an academic and nonregulatory document.

CircRNAs in Endometrial Cancer-A Promising Biomarker: State of the Art.

Endometrial cancer (EC) is one of the most common malignant tumors among women in the 21st century, whose mortality rate is increasing every year. Currently, the diagnosis of EC is possible only after a biopsy. However, it is necessary to find a new biomarker that will help in both the diagnosis and treatment of EC in a non-invasive way. Circular RNAs (circRNAs) are small, covalently closed spherical and stable long non-coding RNAs (lncRNAs) molecules, which are abundant in both body fluids and human tissues and are expressed in various ways. Considering the new molecular classification of EC, many studies have appeared, describing new insights into the functions and mechanisms of circRNAs in EC. In this review article, we focused on the problem of EC and the molecular aspects of its division, as well as the biogenesis, functions, and diagnostic and clinical significance of circRNAs in EC.

Deep Learning for Grading Endometrial Cancer

Endometrial cancer, the fourth most common cancer in females in the United States, with the lifetime risk for developing this disease is approximately 2.8% in women. Precise histologic evaluation and molecular classification of endometrial cancer is important for effective patient management and determining the best treatment modalities. This study introduces EndoNet, which uses convolutional neural networks for extracting histologic features and a vision transformer for aggregating these features and classifying slides based on their visual characteristics into high- and low- grade. The model was trained on 929 digitized hematoxylin and eosin-stained whole-slide images of endometrial cancer from hysterectomy cases at Dartmouth-Health. It classifies these slides into low-grade (Endometroid Grades 1 and 2) and high-grade (endometroid carcinoma FIGO grade 3, uterine serous carcinoma, carcinosarcoma) categories. EndoNet was evaluated on an internal test set of 110 patients and an external test set of 100 patients from the public TCGA database. The model achieved a weighted average F1-score of 0.91 (95% CI: 0.86–0.95) and an AUC of 0.95 (95% CI: 0.89–0.99) on the internal test, and 0.86 (95% CI: 0.80–0.94) for F1-score and 0.86 (95% CI: 0.75–0.93) for AUC on the external test. Pending further validation, EndoNet has the potential to support pathologists without the need of manual annotations in classifying the grades of gynecologic pathology tumors.

Molecular Classification of Endometrial Cancer and Its Impact on Therapy Selection.

Endometrial cancer (EC) accounts for 90% of uterine cancer cases. It is considered not only one of the most common gynecological malignancies but also one of the most frequent cancers among women overall. Nowadays, the differentiation of EC subtypes is based on immunohistochemistry and molecular techniques. It is considered that patients' prognosis and the implementation of the appropriate treatment depend on the cancer subtype. Patients with pathogenic variants in POLE have the most favorable outcome, while those with abnormal p53 protein have the poorest. Therefore, in patients with POLE mutation, the de-escalation of postoperative treatment may be considered, and patients with abnormal p53 protein should be subjected to intensive adjuvant therapy. Patients with a DNA mismatch repair (dMMR) deficiency are classified in the intermediate prognosis group as EC patients without a specific molecular profile. Immunotherapy has been recognized as an effective treatment method in patients with advanced or recurrent EC with a mismatch deficiency. Thus, different adjuvant therapy approaches, including targeted therapy and immunotherapy, are being proposed depending on the EC subtype, and international guidelines, such as those published by ESMO and ESGO/ESTRO/ESP, include recommendations for performing the molecular classification of all EC cases. The decision about adjuvant therapy selection has to be based not only on clinical data and histological type and stage of cancer, but, following international recommendations, has to include EC molecular subtyping. This review describes how molecular classification could support more optimal therapeutic management in endometrial cancer patients.

Роль андрогенов в патогенезе рака эндометрия

Over the past decades, endometrial cancer has become the most common gynecological cancer worldwide. Its increasing incidence cannot be attributed only to the increasing age of women in socially secure countries. The leading risk factor for the endometrial cancer development is obesity, and its epidemic is gradually covering the female population of North Africa, Europe and Asia. Endometrial cancer is pathogenetically associated with hyperestrogenism, and this was the basis for the dualistic theory of clinical and pathological variants proposed by Ya.V. Bohman. The foundations of this theory about the hormonal dependence of endometrial cancer are now being actively supplemented by molecular genetic parameters of the TCGA classification. Recent studies show steroid dependence of endometrial cancer both on estrogens and, to a large extent, on androgens which are directly involved in the complex processes of transformation into estrogens. Published research data, rather contradictory and ambiguous, confirm the antiproliferative role of androgens in the pathogenesis of endometrial cancer. This review analyzes papers on the role of androgens in pathogenesis and their potential clinical antitumor application. Keywords: endometrial cancer, androgens, androgen receptor, classification of endometrial cancer.

Clinical features and impact of p53 status on sporadic mismatch repair deficiency and Lynch syndrome in uterine cancer.

The clinical features of sporadic mismatch repair deficiency (MMRd) and Lynch syndrome (LS) in Japanese patients with endometrial cancer (EC) were examined by evaluating the prevalence and prognostic factors of LS and sporadic MMRd in patients with EC. Targeted sequencing of five LS susceptibility genes (MLH1, MSH2, MSH6, PMS2, and EPCAM) was carried out in 443 patients with EC who were pathologically diagnosed with EC at the National Cancer Center Hospital between 2011 and 2018. Pathogenic variants in these genes were detected in 16 patients (3.7%). Immunohistochemistry for MMR proteins was undertaken in 337 of the 433 (77.9%) EC patients, and 91 patients (27.0%) showed absent expression of at least one MMR protein. The 13 cases of LS with MMR protein loss (93.8%) showed a favorable prognosis with a 5-year overall survival (OS) rate of 100%, although there was no statistically significant difference between this group and the sporadic MMRd group (p = 0.27). In the MMRd without LS group, the 5-year OS rate was significantly worse in seven patients with an aberrant p53 expression pattern than in those with p53 WT (53.6% vs. 93.9%, log-rank test; p = 0.0016). These results suggest that p53 abnormalities and pathogenic germline variants in MMR genes could be potential biomarkers for the molecular classification of EC with MMRd.

Recent Advances in Endometrial Cancer Prevention, Early Diagnosis and Treatment.

Endometrial cancer is the sixth commonest cancer in women worldwide, with over 417,000 diagnoses in 2020. The disease incidence has increased by 132% over the last 30 years and is set to continue to rise in response to an ageing population and increasing global rates of obesity and diabetes. A greater understanding of the mechanisms driving endometrial carcinogenesis has led to the identification of potential strategies for primary disease prevention, although prospective evaluation of their efficacy within clinical trials is still awaited. The early diagnosis of endometrial cancer is associated with improved survival, but has historically relied on invasive endometrial sampling. New, minimally invasive tests using protein and DNA biomarkers and cytology have the potential to transform diagnostic pathways and to allow for the surveillance of high-risk populations. The molecular classification of endometrial cancers has been shown to not only have a prognostic impact, but also to have therapeutic value and is increasingly used to guide adjuvant treatment decisions. Advanced and recurrent disease management has also been revolutionised by increasing the use of debulking surgery and targeted treatments, particularly immunotherapy. This review summarises the recent advances in the prevention, diagnosis and treatment of endometrial cancer and seeks to identify areas for future research.

Abstract IA002: Management of newly diagnosed endometrial cancers and molecular classification

Abstract In the past 50 years, the treatment of this cancer has evolved from a regimen of preoperative radiation therapy followed by hysterectomy, to individualized management consisting of surgical treatment with or without additional therapy depending on whether various risk factors are identified. After the diagnosis of endometrial carcinoma has been histologically confirmed, uterine and extrauterine risk factors affect the probability of retroperitoneal lymph node involvement and subsequent survival. Surgical staging is a critical component for the proper diagnosis and management of all endometrial carcinomas. FIGO stage is the most powerful predictor of prognosis. Surgical staging is feasible by minimally invasive techniques. Patients with significant medical comorbidities who are not acceptable candidates for surgery may be managed by alternative means. Women with EC are diagnosed under the age of 40 may be eligibile for nonoperative management if there is no clear evidence of myometrial invasion. As the contemporary management of EC continues to evolve, and the indications for lymph node dissection remain controversial. Minimally invasive management of EC has increasingly been integrated into standard practice. In 2006, The Cancer Genome Atlas (TCGA) began with studies in glioblastoma and high-grade serous ovarian cancer. The National Institutes of Health committed major resources to TCGA to collect and characterize the genomic landscape of more than 20 cancer types. In 2013, TCGA published findings for endometrial cancers. Only serous and endometrioid subtypes were accrued in the endometrial cancer project. TCGA has reclassified endometrioid and serous endometrial cancers in four broad categories using comprehensive genomic approaches. One-third of the cancers is characterized by microsatellite instability (MSI) and associated hyper-mutation. The cancers without MSI can be further separated into two groups. Serous cases with extensive DNA copy number alterations and genomic instability comprise one group, and endometrioid cases with few or only focal copy number alterations comprise the other. A smaller fourth sub-group contains samples with very high mutation rates and is characterized by mutations in POLE. Molecular features can be distinctly overlaid onto these four sub-classifications, and each have important clinical implications that are currently being used in both clinical practice and clinical trial design. In this educational presentation, we will discuss the management of newly diagnosed endometrial cancers, review the molecular classification of endometrial cancers, and identify approaches that incorporate these findings into clinical care and clinical trial design. Citation Format: Douglas A. Levine. Management of newly diagnosed endometrial cancers and molecular classification [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 IA002.