Dear Colleagues,

The incidence of endometrial disease has increased gradually over the past decade. Obesity and aging are the main risk factors related to the onset, not only of endometrial cancer (EC), but also of its precursor lesions, such as atypical hyperplasia (AH) and endometrioid intraepithelial neoplasia (EIN).

In 2013, molecular classification by the Cancer Genome Atlas (TCGA) Research Network was introduced, followed by validation of a practical model known as ProMisE (Proactive Molecular Risk Classifier for Endometrial Cancer). Together, these revolutionized the EC risk classification with the aim to improve the clinical management and personalization of EC therapy. Based on type of mutations and somatic copy-number variations, genome, exome sequencing, and microsatellite instability (MSI) assay, EC is divided into four different groups: polymerase epsilon (POLE) ultramutated, MSI hypermutated, copy-number (CN) low, and CN high. Survival outcomes and recurrence risk differs for each subgroup. Numerous recent studies, aiming to define different possible characteristics within the same subgroups, have identified other alterations in potential target pathways. This evidence could prove useful, especially in EC with poor prognosis such as p53-mutant and non-endometrial histotype. Among endometrial diseases, the optimal management of EC precursor lesions remains for debate. In an era with increasing incidence of such pathologies in premenopause, and where the age of first pregnancy tends to be older, identifying patients with a higher risk of progression in EC with precise molecular analysis will help determine the appropriate fertility-sparing treatment as well as possible roles of target therapies.

This special issue of CEOG focuses on new insights into molecular mechanisms of endometrial disease and how these could help establish tailored management, in light of current implications and further perspectives.

Assis. Prof. Dr. Violante Di Donato and Dr. Ilaria Cuccu
Guest Editors