REVIEW article
Front. Oncol.
Sec. Cancer Genetics
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1633260
POLE-mutated endometrial cancer: new perspectives on the horizon?
Provisionally accepted
Daniele Fanale
Lidia Rita CorsiniPaola PirainoErika Pedone
Chiara Brando
Tancredi Didier Bazan RussoPietro FerraroAlisia SimoneSilvia ContinoOrnella PrestifilippoUgo RandazzoAmbra GiurintanoCarla Ferrante Bannera
Antonio Galvano
Lorena IncorvaiaGianfranco Pernice
SALVATORE VIENIGianni Pantuso
Calogero CipollaAntonio Giulio Giannone
Giuseppe Badalamenti
Antonio Russo
Viviana Bazan*- University of Palermo, Palermo, Italy
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Endometrial carcinoma (EC) is one of the most common gynecological cancers showing a survival rate of 15-17% in the case of advanced disease. Based on the mutational burden and copy number alteration, EC is classified into four different molecular subgroups: POLE-mutated (ultramutated), microsatellite unstable (hypermutated), low copy number (endometrioid), and high copy number (serous-like). Despite the high tumour grading, the ultramutated subtype, accounting for about 8-10% of all ECs, showed favourable prognostic potential, enhanced immune response, and excellent clinical outcomes. Somatic POLE alterations have been found in 6-10% of ECs, whereas germline pathogenic variants have been reported only in 0.25-4% of cases. Germline POLE alterations are linked to genome instability and are associated with onset of hereditary tumours, including colorectal cancer and EC. Emerging data suggests that knowledge of POLE mutational status could be clinically important, as ultramutated ECs may be more likely to respond to immunotherapy.In this Review, we will investigate the role of germline/somatic POLE genetic alterations in EC, discussing the potential future theranostic applications and evaluating the benefit of performing a routine genetic testing, in order to adopt prevention and surveillance strategies in germline POLE mutation carriers.
Keywords: endometrial cancer, Exonuclease domain mutations, Germline/somatic POLE variants, Microsatellite Instability, pole, POLE-ultramutated subtype, prognosis
Received: 22 May 2025; Accepted: 11 Aug 2025.
Copyright: © 2025 Fanale, Corsini, Piraino, Pedone, Brando, Bazan Russo, Ferraro, Simone, Contino, Prestifilippo, Randazzo, Giurintano, Bannera, Galvano, Incorvaia, Pernice, VIENI, Pantuso, Cipolla, Giulio Giannone, Badalamenti, Russo and Bazan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Viviana Bazan, University of Palermo, Palermo, Italy
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