What’s behind the Scenes? New Insights in Endometrial Cancer Management and Risk Stratification

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Epidemiology and Prevention".

Deadline for manuscript submissions: 20 October 2025 | Viewed by 7719

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Guest Editor
Fondazione Policlinico Universitario A. Gemelli, IRCCS, UOC Ginecologia Oncologica, Dipartimento per la salute della Donna e del Bambino e della Salute Pubblica, Roma, Italy
Interests: endometrial cancer; molecular classification; surgical staging; surgery; targeted therapy; gynecologic oncology; precision medicine; immunohistochemistry
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Special Issue Information

Dear Colleagues, 

Endometrial cancer (EC) is the fourth most widespread malignancy in developed countries and the first gynecologic cancer in the United States. Its incidence is expected to double in the next 10 years. In the last several years, Cancer Genome Atlas (TCGA) results have led to a revision of EC classification: four genomic classes with different oncological outcomes (POLE (good prognosis); high-copy-number tumors with TP53 mutations (poor prognosis); hypermutated tumors with microsatellite instability (MSI) (good to intermediate prognosis); and low-copy-number tumors (good to intermediate prognosis)). This innovative approach to the definition of EC has led to a new tendency to reframe EC clinical and pathological history. The TGCA molecular classification has since received external and real-world validation thanks to a growing body of evidence confirming the validity of this new EC stratification (PORTEC 3, etc.). A further fundamental step was the transition from tumor DNA sequencing to the immunohistochemical (IHC) analysis of the molecular classification with the ProMisE study, which outlined four different prognostic EC sub-groups almost superimposable to the TCGA genomic classes. These subgroups were defined as: POLE-mutated (good prognosis), p53-abnormal (poor prognosis), mismatch repair deficient (MMRd; good to intermediate prognosis), and p53-wild type (good to intermediate prognosis). Notably, the p53-wild type, also known as “no specific molecular profile” (NSMP), represents the most prevalent EC subgroup (39–64% within the overall EC population). So, other molecular markers have been investigated to further understand the remaining knowledge gaps. Recently, on these bases, the ESGO/ESTRO/ESP guidelines classification system was introduced, combining the pathological and clinical features with the new molecular information in EC risk stratification and management. Waiting for the result of the PORTEC 4a study that will define the correct therapeutic management with adjuvant therapy and the EUGENIE trial that will indicate the proper surgical staging for each molecular class, the aim of this Special Issue is focused on describing the updates related to the classification and management of EC in the context of this new molecular era.

Dr. Emanuele Perrone
Guest Editor

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Keywords

  • endometrial cancer
  • molecular classification
  • surgical staging, surgery
  • target therapy
  • gynecologic oncology
  • precision medicine
  • immunohistochemistry

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Published Papers (2 papers)

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17 pages, 2557 KiB  
Article
Cervical Fluids Are a Source of Protein Biomarkers for Early, Non-Invasive Endometrial Cancer Diagnosis
by Elena Martinez-Garcia, Eva Coll-de la Rubia, Antoine Lesur, Gunnar Dittmar, Antonio Gil-Moreno, Silvia Cabrera and Eva Colas
Cancers 2023, 15(3), 911; https://doi.org/10.3390/cancers15030911 - 31 Jan 2023
Cited by 9 | Viewed by 3304
Abstract
Background: Abnormal uterine bleeding is the main symptom of endometrial cancer (EC), but it is highly nonspecific. This represents a huge burden for women’s health since all women presenting with bleeding will undergo sequential invasive tests, which are avoidable for 90–95% of those [...] Read more.
Background: Abnormal uterine bleeding is the main symptom of endometrial cancer (EC), but it is highly nonspecific. This represents a huge burden for women’s health since all women presenting with bleeding will undergo sequential invasive tests, which are avoidable for 90–95% of those women who do not have EC. Methods: This study aimed to evaluate the potential of cervical samples collected with five different devices as a source of protein biomarkers to diagnose EC. We evaluated the protein quantity and the proteome composition of five cervical sampling methods. Results: Samples collected with a Rovers Cervex Brush® and the HC2 DNA collection device, Digene, were the most suitable samples for EC proteomic studies. Most proteins found in uterine fluids were also detected in both cervical samples. We then conducted a clinical retrospective study to assess the expression of 52 EC-related proteins in 41 patients (22 EC; 19 non-EC), using targeted proteomics. We identified SERPINH1, VIM, TAGLN, PPIA, CSE1L, and CTNNB1 as potential protein biomarkers to discriminate between EC and symptomatic non-EC women with abnormal uterine bleeding in cervical fluids (AUC > 0.8). Conclusions: This study opens an avenue for developing non-invasive protein-based EC diagnostic tests, which will improve the standard of care for gynecological patients. Full article
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15 pages, 1029 KiB  
Review
Lynch Syndrome and Gynecologic Tumors: Incidence, Prophylaxis, and Management of Patients with Cancer
by Ilaria Capasso, Angela Santoro, Emanuela Lucci Cordisco, Emanuele Perrone, Francesca Tronconi, Ursula Catena, Gian Franco Zannoni, Giovanni Scambia, Francesco Fanfani, Domenica Lorusso and Simona Duranti
Cancers 2023, 15(5), 1400; https://doi.org/10.3390/cancers15051400 - 22 Feb 2023
Cited by 10 | Viewed by 3843
Abstract
This review provides a comprehensive update on recent evidence regarding gynecologic tumors associated with Lynch Syndrome (LS). Endometrial cancer (EC) and ovarian cancer (OC) are the first and second most common gynecologic malignancies in developed countries, respectively, and LS is estimated to be [...] Read more.
This review provides a comprehensive update on recent evidence regarding gynecologic tumors associated with Lynch Syndrome (LS). Endometrial cancer (EC) and ovarian cancer (OC) are the first and second most common gynecologic malignancies in developed countries, respectively, and LS is estimated to be the hereditary cause in 3% of both EC and OC. Despite the increasing evidence on LS-related tumors, few studies have analyzed the outcomes of LS-related EC and OC stratified by mutational variant. This review aims to provide a comprehensive overview of the literature and comparison between updated international guidelines, to help outline a shared pathway for the diagnosis, prevention, and management of LS. Through the widespread adoption of the immunohistochemistry-based Universal Screening, LS diagnosis and identification of mutational variants could be standardized and recognized by international guidelines as a feasible, reproducible, and cost-effective method. Furthermore, the development of a better understanding of LS and its mutational variants will support our ability to better tailor EC and OC management in terms of prophylactic surgery and systemic treatment in the light of the promising results shown by immunotherapy. Full article
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