Alignment of Molecular Classification Between Diagnosis and Recurrence in Endometrial Cancer: Lessons from a Single-Institution Experience to Inform Future Pathways

<b>Introduction</b>: Endometrial carcinoma (EC) is the most prevalent gynecological cancer. It is characterized by a clinical, pathological, and prognostic trajectory that has become inextricably linked to the disease's molecular profile. Therefore, it is imperative to examine its relevance across all facets associated with the disease. <b>Methods</b>: This is a single-center retrospective study to assess tumor molecular profile concordance between EC diagnosis and recurrence. All patients who underwent hysterectomy for EC between 2016 and 2020 were included. <b>Results</b>: In total, 221 cases of EC were collected. In total, 18 recurrences were found. In two cases, there was a molecular classification (MC) change: an MMR-deficient endometrioid EC shifted to a "multiple classifier" subtype. The second, an NSMP subtype, at second recurrence revealed a switched MC to an aberrant mutated p53 profile. This discordance rate was non-significant in our cohort. However, considering the lack of evidence, it opens new insights to be revealed. <b>Conclusions</b>: This is the first study focusing on the discordance rate of MCs in EC relapses compared to the initial diagnosis. Future large-scale retrospective and prospective multicenter studies are essential for exploring this aspect.