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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 3042

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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

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Keywords

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

Published Papers (2 papers)

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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
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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 - 06 May 2023
Cited by 1 | Viewed by 1369
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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