What’s behind the Scenes? New Insights in Endometrial Cancer Management and Risk Stratification

Dear Colleagues, 

Endometrial cancer (EC) is the fourth most widespread malignancy in developed countries and the first gynecologic cancer in the United States. Its incidence is expected to double in the next 10 years. In the last several years, Cancer Genome Atlas (TCGA) results have led to a revision of EC classification: four genomic classes with different oncological outcomes (POLE (good prognosis); high-copy-number tumors with TP53 mutations (poor prognosis); hypermutated tumors with microsatellite instability (MSI) (good to intermediate prognosis); and low-copy-number tumors (good to intermediate prognosis)). This innovative approach to the definition of EC has led to a new tendency to reframe EC clinical and pathological history. The TGCA molecular classification has since received external and real-world validation thanks to a growing body of evidence confirming the validity of this new EC stratification (PORTEC 3, etc.). A further fundamental step was the transition from tumor DNA sequencing to the immunohistochemical (IHC) analysis of the molecular classification with the ProMisE study, which outlined four different prognostic EC sub-groups almost superimposable to the TCGA genomic classes. These subgroups were defined as: POLE-mutated (good prognosis), p53-abnormal (poor prognosis), mismatch repair deficient (MMRd; good to intermediate prognosis), and p53-wild type (good to intermediate prognosis). Notably, the p53-wild type, also known as “no specific molecular profile” (NSMP), represents the most prevalent EC subgroup (39–64% within the overall EC population). So, other molecular markers have been investigated to further understand the remaining knowledge gaps. Recently, on these bases, the ESGO/ESTRO/ESP guidelines classification system was introduced, combining the pathological and clinical features with the new molecular information in EC risk stratification and management. Waiting for the result of the PORTEC 4a study that will define the correct therapeutic management with adjuvant therapy and the EUGENIE trial that will indicate the proper surgical staging for each molecular class, the aim of this Special Issue is focused on describing the updates related to the classification and management of EC in the context of this new molecular era.

Dr. Emanuele Perrone
Guest Editor

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• endometrial cancer
• molecular classification
• surgical staging, surgery
• target therapy
• gynecologic oncology
• precision medicine
• immunohistochemistry