Introduction/Background Nowadays, immunohistochemistry analysis together with POLE sequencing (genomic profiling-based model, GP-M) is the gold-standard for endometrial cancer (EC) classification into molecular classes: POLE-mutated, no specific molecular profile, mismatch repair deficient (MMRd), and p53-abnormal (p53abn). This study aims to investigate the non-inferiority of immunohistochemistry model (IHC-M) in classifying ECs compared to the standard (GP-M) in terms of oncologic outcomes.

Methodology All presumed uterine-confined ECs undergoing surgical staging at Fondazione Policlinico Universitario A. Gemelli and University Hospitals of Leuven were retrospectively included. Patients classified by IHC-M were stratified into: MMR-proficient (MMRp) and estrogen receptor (ER) positive, MMRp and ER-negative, MMRd, and p53abn. First, a case-control comparison was performed with a control cohort of ECs classified by GP-M. Second, a propensity match analysis was performed: ECs classified by IHC-M were matched in a 3:1 ratio with patients classified by GP-M.

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Abstract #447 Figure 1

The Kaplan-Meier survival curves for disease-free survival of the two cohorts stratified according to the two models

Results 1592 ECs were included (1321 classified by IHC-M, and 271 classified by GP-M). Age, BMI, histology, and adjuvant treatment differed between the two cohorts (p<0.05). The Kaplan-Meier survival curves for disease-free survival demonstrated similar validity of the two models in stratifying the two cohorts (p<0.0001). Applying the propensity score match and balancing the two cohorts, the survival analysis demonstrated a non-inferiority of IHC-M in ECs classification compared to GP-M (p<0.0001). Moreover, ROC curves showed overlapping AUC: 0.77 (0.66–0.87) for IHC-M and 0.72 (0.63–0.81) for GP-M.

Conclusion In this large retrospective EC series, the IHC-M showed superimposable classification power compared to the GP-M in terms of oncologic outcomes. This study may lay basis to further investigate the concreate real-life clinical impact of POLE sequencing in molecular classification and the potential role of ER receptor for further classifying EC patients. Moreover, our results further reinforce the evidence in favour of reconsidering the ER status especially in NSMP subgroup. Longer follow-up and prospective studies are necessary.

Disclosures Nothing to disclose