Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Enhanced risk stratification in early-stage endometrial cancer: Integrating Molucular-L1CAM Classification and Simplified L1CAM/p53 Categorization

Version 1 : Received: 10 August 2023 / Approved: 10 August 2023 / Online: 11 August 2023 (08:38:07 CEST)

A peer-reviewed article of this Preprint also exists.

Joe, S.; Lee, M.; Kang, J.; Kim, J.; Hong, S.-H.; Lee, S.J.; Lee, K.H.; Lee, A. Enhanced Risk Stratification in Early-Stage Endometrial Cancer: Integrating POLE through Droplet Digital PCR and L1CAM. Cancers 2023, 15, 4899. Joe, S.; Lee, M.; Kang, J.; Kim, J.; Hong, S.-H.; Lee, S.J.; Lee, K.H.; Lee, A. Enhanced Risk Stratification in Early-Stage Endometrial Cancer: Integrating POLE through Droplet Digital PCR and L1CAM. Cancers 2023, 15, 4899.

Abstract

Aim: To improve risk stratification in early-stage endometrial cancer (EC), we performed mo-lecular classification, and L1CAM immunohistochemistry (IHC) for additional risk assessment. Method: We analyzed archival tumor tissue from 247 early-stage EC patients. POLE mutations were detected using a Droplet digital polymerase chain reaction assay and Sanger sequencing, while the mismatch repair (MMR) status was determined by MMR protein IHC and MSI test. Additionally, we conducted IHC of p53 and L1CAM. Results: The 247 ECs were categorized into four subgroups: POLE-mutated (13.0%), MMR-deficient (27.9%), p53-abnormal (8.5%), and non-specific molecular profile (NSMP, 50.6%). We further subcategorized NSMP subgroup into NSMP-L1CAMneg (44.9%) and NSMP-L1CAMpos (5.7%), which we refer to as the molecu-lar-L1CAM classification. The molecular-L1CAM classification was an independent prognostic factor for recurrence-free survival (RFS) and overall survival (OS) (p <0.001, each). Similarly, the simplified L1CAM-p53 categorization, for practical use, remained an independent prognostic factor for RFS and OS (p <0.001, p =0.003, respectively). Conclusion: Integrating the molecu-lar-L1CAM classification or the simplified L1CAM/p53 categorization can enhance risk stratifi-cation in early-stage EC, providing valuable prognostic information to guide treatment deci-sions and improve patient outcomes.

Keywords

early-stage endometrial cancer; molecular classification; L1CAM; risk stratification; prognosis

Subject

Medicine and Pharmacology, Pathology and Pathobiology

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