Prognostic and therapeutic implication of molecular classification including L1CAM expression in high-risk endometrial cancer

Andreas Kleppe; Kristina Lindemann; Wanja Kildal; Kari Anne R Tobin; Manohar Pradhan; Ljiljana Vlatkovic; Maria X Isaksen; Håvard E Danielsen; Hanne A Askautrud; Gunnar B Kristensen

doi:10.1016/j.ygyno.2024.11.005

Prognostic and therapeutic implication of molecular classification including L1CAM expression in high-risk endometrial cancer

Gynecol Oncol. 2024 Nov 15:192:80-88. doi: 10.1016/j.ygyno.2024.11.005. Online ahead of print.

Affiliations

¹ Institute for Cancer Genetics and Informatics, Division of Cancer Medicine, Oslo University Hospital, Oslo, Norway; Department of Informatics, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway; Centre for Research-based Innovation Visual Intelligence, UiT The Arctic University of Norway, Tromsø, Norway.
² Department of Surgical Oncology, Section for gynecological oncology, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
³ Institute for Cancer Genetics and Informatics, Division of Cancer Medicine, Oslo University Hospital, Oslo, Norway.
⁴ Institute for Cancer Genetics and Informatics, Division of Cancer Medicine, Oslo University Hospital, Oslo, Norway; Nuffield Division of Clinical Laboratory Sciences, University of Oxford, Oxford, United Kingdom.
⁵ Institute for Cancer Genetics and Informatics, Division of Cancer Medicine, Oslo University Hospital, Oslo, Norway; Department of Surgical Oncology, Section for gynecological oncology, Oslo University Hospital, Oslo, Norway. Electronic address: gunnar.b.kristensen@gmail.com.

PMID: 39549540
DOI: 10.1016/j.ygyno.2024.11.005

Abstract

Introduction: The role of molecular classification and L1CAM in high-risk endometrial cancer is uncertain. We aimed to determine the association of molecular profiling and L1CAM with patterns of relapse and survival.

Material and methods: This retrospective cohort study included patients referred to Department for Gynecologic Oncology, Oslo University Hospital between January 1, 2006 and December 31, 2017. L1CAM expression and molecular profiling according to ProMisE was performed. Main outcome was time to recurrence (TTR) and cancer specific survival (CSS).

Results: Of 489 patients, 486 could be molecular classified. Thirty-seven (8 %) had POLE mutated tumors, 148 (30 %) had MMRd tumors, 189 (39 %) had p53 abnormal tumors, and 112 (23 %) had NSMP tumors. High L1CAM expression was observed in 256 (53 %), low in 227 (46 %) tumors (6 (1 %) missing). ProMisE was significant for TTR but not for CSS in multivariable analysis. L1CAM was significant in multivariable analysis for both TTR and CSS. In a multivariable model with ProMisE and L1CAM expression in the same multivariable model, ProMisE lost significance while L1CAM remained significant. Patients with POLE mutated tumors entailed an excellent prognosis while patients with p53 abnormal or L1CAM overexpressing tumors entailed a poor prognosis with a high frequency of distant recurrences. Patients with MMRd tumors, NSMP and p53 abnormal tumors with low L1CAM had an intermediate prognosis.

Conclusions: L1CAM is an additional adverse factor in the p53 abnormal and NSMP groups. These groups need special attention in studies intensifying adjuvant treatment.

Keywords: Adjuvant therapy; Endometrial cancer; High-risk; L1CAM expression; Molecular classification; Prognosis; Recurrence location.