Validation of molecular classification on diagnostic biopsy in endometrial carcinoma: the first step for a tailored approach

Objective: To validate the concordance of histologic subtype, tumor grade, molecular classification, and risk group between pre-operative endometrial biopsy and final hysterectomy specimens in patients with endometrial cancer (EC). Methods: The PReOperative MOlecular Biopsy (ProMobi) study is a prospective, monocentric, observational study conducted from September 2023 to March 2024. All patients with suspicious finding for EC were included. Diagnosis was achieved by a pre-operative biopsy. On the latter, histopathology analysis, tumor grade, immunohistochemical (IHC) markers, molecular classification and risk group were determined. The same was performed on the final hysterectomy. Concordance was evaluated using Cohen's κ statistic. Results: A total of 50 consecutive patients were included. Molecular classification showed perfect concordance for POLE mutations (Cohen's κ=1.0) and strong concordance for p53 wild-type and abnormal subtypes (Cohen's κ=0.87). Similarly, mismatch repair-deficient/microsatellite instability and mismatch repair-proficient/microsatellite stable statuses achieved strong concordance (Cohen's κ=0.81), with an overall κ of 0.88 for molecular classification. Histotype agreement was nearly perfect (Cohen's κ=0.90), and tumor grade showed strong concordance (Cohen's κ=0.80). Risk group concordance was strong for group 1 (Cohen's κ=0.91), group 2 (0.94), and group 4 (0.96), with perfect concordance for group 3 (Cohen's κ=1.0). Overall risk group concordance was very high (Cohen's κ=0.95). Conclusion: This study demonstrates a high concordance in molecular classification, histotype, tumor grade and risk group between hysteroscopic biopsy and hysterectomy specimens. These findings establish that a personalized surgical approach to EC patients can be guided by molecular classification on pre-operative biopsy.