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Molecular Classification of Endometrial Cancer and Its Impact on Therapy Selection. Int. J. Mol. Sci. 2024, 25, 5893. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/ijms25115893](10.3390/ijms25115893)  \nAcademic Editor: Seung-Yup Ku  \nReceived: 17 April 2024  \nRevised: 21 May 2024  \nAccepted: 27 May 2024  \nPublished: 28 May 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Department of Pneumonology, Oncology and Allergology, Medical University of Lublin, 20-090 Lublin, Poland; [nataliagalant@umlub.pl](nataliagalant@umlub.pl) (N.G.); [pawel.krawczyk@umlub.pl](pawel.krawczyk@umlub.pl) (P.K.); [marcin.nicos@umlub.pl](marcin.nicos@umlub.pl) (M.N.); [janusz.milanowski@umlub.pl](janusz.milanowski@umlub.pl) (J.M.)  \n2 II Department of Gynecology, Medical University of Lublin, 20-090 Lublin, Poland; [marta.monist@umlub.pl](marta.monist@umlub.pl)  \n3 Institute of Genetics and Immunology GENIM LCC, 20-609 Lublin, Poland; [obara12lb@interia.pl](obara12lb@interia.pl) (A.O.); [luk.gajek@gmail.com](luk.gajek@gmail.com) (Ł.G.)  \n4 Department of Oncology, Polish Mother’s Memorial Hospital-Research Institute, 93-338 Łód´z, Poland; [ewakalinka@wp.pl](ewakalinka@wp.pl)  \n* Correspondence: [anna.grenda@umlub.pl](anna.grenda@umlub.pl)  \nAbstract: 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.  \nKeywords: endometrial cancer; molecular subtypes; personalized treatment  \n1. Introduction  \nEndometrial cancer (EC) is caused by the growth of the mucous membrane lining the uterus [1], and, along with rarer uterine sarcoma, it is classified as a type of uterine cancer. Endometrial cancer accounts for 90% of uterine cancer ca","cbCaikwSTl7dnzM9","https://ap.wps.com/l/cbCaikwSTl7dnzM9","pdf",1068263,18,"English","# Introduction\n## Molecular subtypes of endometrial cancer\n## Rationale for molecular classification in therapy selection","[{\"question\":\"How does molecular classification influence therapy selection in endometrial cancer?\",\"answer\":\"The review emphasizes that adjuvant therapy decisions should include molecular subtyping, not only clinical stage and histology. Different subtypes support different therapeutic approaches, including targeted therapy and immunotherapy.\"},{\"question\":\"What are the main molecular subtypes of endometrial cancer described?\",\"answer\":\"The document lists four molecular subtypes: POLEmut, dMMR with MSI-High, p53abn, and NSMP. These correspond to distinct molecular features used for patient stratification.\"},{\"question\":\"Which endometrial cancer subtype is associated with the most favorable and the poorest outcomes?\",\"answer\":\"Patients with pathogenic variants in POLE are described as having the most favorable outcome, while those with abnormal p53 protein have the poorest outcome.\"}]","Molecular Classification of Endometrial Cancer and Its Impact on Therapy Selection | PDF",1790020889,45]