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Endometrial Carcinoma: Targeted Therapies and Future Perspectives
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Endometrial Carcinoma: Targeted Therapies and Future Perspectives

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (15 July 2023) | Viewed by 7572

Special Issue Editor

Dr. Angela Santoro

E-Mail Website
Guest Editor
Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
Interests: gynecological neoplasms; breast cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Endometrial cancer represents a real global public health problem, accounting for 2.1% cancer deaths, making it the fourth most common cancer in women. Moreover, its global incidence and mortality rates are still rising each year, supporting the idea that therapeutical strategies need to be urgently revised and improved. 

This Special Issue aims to shed light on the recent advances in relation to the molecular background of endometrial cancer using large genomic assays. 

Enormous progresses have been made from the publication of the 2013 TGCA classification of endometrial cancer. Currently, the international guidelines are promoting a histomolecular approach in order to perform a more accurate prognostic risk stratification to improve the discovery and experimentation of more innovative targeted therapeutics. 

Along this line, the present Special Issue will provide a comprehensive review of the current molecular discoveries on endometrial cancer and discuss the future implications of the new histomolecular diagnostic approach in prognostic risk evaluation and in therapeutic strategies.

Dr. Angela Santoro
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • molecular background
  • precision medicine
  • histomolecular diagnosis
  • targeted therapies
  • clinical trials
  • overall survival
  • disease free survival
  • endometrial cancer
  • whole genomic assay
  • molecular biomarkers

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Further information on MDPI's Special Issue policies can be found here.

Published Papers (3 papers)

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Research

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13 pages, 930 KiB  
Article
Comparison of Methods for Testing Mismatch Repair Status in Endometrial Cancer
by Marta Mendiola, Victoria Heredia-Soto, Ignacio Ruz-Caracuel, Amparo Baillo, Jorge Luis Ramon-Patino, Francisco Javier Escudero, Maria Miguel, Alberto Pelaez-Garcia, Alicia Hernandez, Jaime Feliu, David Hardisson and Andres Redondo
Int. J. Mol. Sci. 2023, 24(19), 14468; https://doi.org/10.3390/ijms241914468 - 23 Sep 2023
Cited by 8 | Viewed by 2901
Abstract
Approximately 20–30% of endometrial carcinomas (EC) are characterized by mismatch repair (MMR) deficiency (dMMR) or microsatellite instability (MSI), and their testing has become part of the routine diagnosis. The aim of this study was to establish and compare the MMR status using various [...] Read more.
Approximately 20–30% of endometrial carcinomas (EC) are characterized by mismatch repair (MMR) deficiency (dMMR) or microsatellite instability (MSI), and their testing has become part of the routine diagnosis. The aim of this study was to establish and compare the MMR status using various approaches. Immunohistochemistry (IHC), PCR-based MSI, and the detection of defects in the four key MMR genes (MLH1, PMS2, MSH2, and MSH6) via methylation-specific multiplex ligation-dependent probe amplification (MLPA) and targeted next-generation sequencing (NGS) were performed. MSH3 expression was also evaluated. A set of 126 early-stage EC samples were analyzed, 53.2% of which were dMMR and 46.8% of which were proficient MMR (pMMR) as determined using IHC, whereas 69.3% were classified as microsatellite stable, while 8.8% and 21.9% were classified MSI-low (MSI-L) and MSI-high (MSI-H), respectively. In total, 44.3% of the samples showed genetic or epigenetic alterations in one or more genes; MLH1 promoter methylation was the most common event. Although acceptable concordance was observed, there were overall discrepancies between the three testing approaches, mainly associated with the dMMR group. IHC had a better correlation with MMR genomic status than the MSI status determined using PCR. Further studies are needed to establish solid conclusions regarding the best MMR assessment technique for EC. Full article
(This article belongs to the Special Issue Endometrial Carcinoma: Targeted Therapies and Future Perspectives)
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11 pages, 3129 KiB  
Article
Association of Membranous WNT-1 and Nuclear mTOR with Endometrial Cancer Grade
by Milosz Pietrus, Kazimierz Pitynski, Marcin Waligora, Katarzyna Milian-Ciesielska, Artur Ludwin, Maciej W. Socha and Klaudia Skrzypek
Int. J. Mol. Sci. 2023, 24(9), 8342; https://doi.org/10.3390/ijms24098342 - 6 May 2023
Cited by 4 | Viewed by 2113
Abstract
Endometrial cancer remains a common cancer affecting the female reproductive system. There is still a need for more efficient ways of determining the degree of malignancy and optimizing treatment. WNT and mTOR are components of signaling pathways within tumor cells, and dysfunction of [...] Read more.
Endometrial cancer remains a common cancer affecting the female reproductive system. There is still a need for more efficient ways of determining the degree of malignancy and optimizing treatment. WNT and mTOR are components of signaling pathways within tumor cells, and dysfunction of either protein is associated with the pathogenesis of neoplasms. Therefore, the aim of our study was to assess the impact of subcellular WNT-1 and mTOR levels on the clinical course of endometrial cancer. WNT-1 and mTOR levels in the plasma membrane, nucleus, and cytoplasm were evaluated using immunohistochemical staining in a group of 64 patients with endometrial cancer of grades 1–3 and FIGO stages I–IV. We discovered that the levels of WNT-1 and mTOR expression in the cellular compartments were associated with tumor grade and staging. Membranous WNT-1 was negatively associated, whereas cytoplasmic WNT-1 and nuclear mTOR were positively associated with higher grading of endometrial cancer. Furthermore, nuclear mTOR was positively associated with FIGO stages IB–IV. To conclude, we found that the assessment of WNT-1 in the cell membrane may be useful for exclusion of grade 3 neoplasms, whereas cytoplasmic WNT-1 and nuclear mTOR may be used as indicators for confirmation of grade 3 neoplasms. Full article
(This article belongs to the Special Issue Endometrial Carcinoma: Targeted Therapies and Future Perspectives)
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Review

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16 pages, 287 KiB  
Review
Beyond the WHO 2020 Classification of Female Genital Tumors: Types of Endometrial Cancer: A Pathological and Molecular Focus on Challenging Rare Variants
by Angela Santoro, Giuseppe Angelico, Antonio Travaglino, Frediano Inzani, Damiano Arciuolo, Antonio d’Amati, Nicoletta D’Alessandris, Giulia Scaglione, Michele Valente, Belen Padial Urtueta, Francesca Addante, Nadine Narducci, Giuseppe Pannone, Emma Bragantini, Antonio Raffone, Antonino Mulè and Gian Franco Zannoni
Int. J. Mol. Sci. 2024, 25(19), 10320; https://doi.org/10.3390/ijms251910320 - 25 Sep 2024
Cited by 1 | Viewed by 2051
Abstract
Endometrial carcinoma is a heterogeneous group of malignancies characterized by distinct histopathological features and genetic underpinnings. The 2020 WHO classification has provided a comprehensive framework for the categorization of endometrial carcinoma. However, it has not fully addressed the spectrum of uncommon entities that [...] Read more.
Endometrial carcinoma is a heterogeneous group of malignancies characterized by distinct histopathological features and genetic underpinnings. The 2020 WHO classification has provided a comprehensive framework for the categorization of endometrial carcinoma. However, it has not fully addressed the spectrum of uncommon entities that are currently not recognized by the 2020 WHO and have only been described in the form of small case series and case reports. These neoplasms represent a real diagnostic challenge for pathologists; furthermore, their therapeutic management still remains controversial and information regarding tumor prognosis is very limited. This review aims to elucidate these lesser-known variants of endometrial carcinoma. We discuss the challenges of identifying these rare subtypes and the molecular alterations associated with them. Furthermore, we propose the need for expanded classification systems that include these variants to enhance clinical outcomes and research efforts. We believe that a better histological typing characterization of these entities may lead to more reproducible and accurate diagnoses and more personalized treatments. By raising awareness of these rare entities, we also hope to encourage further investigation and integration into clinical practice to improve patient care in endometrial carcinoma. Full article
(This article belongs to the Special Issue Endometrial Carcinoma: Targeted Therapies and Future Perspectives)
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