Molecular classification of endometrial cancer: Impact on adjuvant treatment planning

The traditional histopathological analysis of endometrial cancer (EC) is the main risk group classification tool (low, intermediate, high-intermediate, and high) for the implementation of adjuvant treatment. The International Federation of Gynecology and Obstetrics staging system of EC has incorporated a new molecular classification that serves as a new triage tool for optimal treatment planning for these patients. Our study aimed to investigate the prognostic role of the new molecular classification in EC.

A prospective study was conducted in the 1^st Department of Obstetrics and Gynecology from January 1, 2022, to March 30, 2024, and included all new EC cases that presented the multidisciplinary tumor (MDT) board after surgery. We considered the traditional pathologic analysis and new molecular classification after performing tests on microsatellite instability (MSI), DNA polymerase epsilon (POLE) mutation, and p53 immunohistochemistry testing.

The study included 65 patients with presumed early endometrial. All patients underwent surgery and subsequent molecular testing. Among the patients, 35 (54%) had a "positive" result in all of the three markers of molecular classification: 14 patients presented with MSI-H, 5 with POLE gene mutation, and 17 with p53 abnormal expression. One case of multiple classifiers was presented. After the integration of molecular classification, a change was observed in the final MDT board decision in 23 cases (35.4%), including six cases of overtreatment and 17 cases of undertreatment, with statistical significance (P = 0.03469).

The data suggest that the new molecular classification, that is, testing for POLE mutation, MSI, and p53 mutation and for endometrial carcinoma, is a valuable tool for the recurrence risk prognosis and improved planning of adjuvant treatment for EC.