How Can “No Specific Molecular Profile” Heterogeneity be Reduced in Molecularly Classified Endometrial Cancer?: Prognostic Significance of L1 Cell Adhesion Molecule

Abstract

This study aims to investigate the role of L1 cell adhesion molecule (L1CAM) in the prognostic assessment of endometrial cancers that have been depicted as having no specific molecular profile (NSMP) in molecular classification. This is a retrospective review of 150 patients who received the diagnosis of endometrial cancer and underwent surgery at the study center between January 2008 and January 2022. When evaluating L1CAM immunohistochemical staining, scoring was done according to the percentage of positivity in tumor cells. Accordingly, score 0 = 0%, score 1=1% to 10%, score 2 = >10% to 50% and score 3 = >50%. If the staining in tumor cells was ≥10% (scores 2 and 3), it was considered positive. The patients with L1CAM positivity had significantly more frequent lymphovascular space invasion and lymph node metastasis than patients with L1CAM negativity (P = 0.013 and P = 0.007). L1CAM expression was strongly associated with mutant p53 (P = 0.003). Recurrence was significantly higher (P = 0.001) and overall survival and progression-free survival were significantly lower in patients with L1CAM positivity (P = 0.001 for both). Seventy-nine patients (52.7%) were put into NSMP group. About 84.8% of them (n = 67) were L1CAM negative and 15.2% of them (n = 12) were L1CAM-positive. Recurrence was significantly higher (P = 0.001) and overall survival and progression-free survival were significantly lower in patients with NSMP who were positive for L1CAM (P = 0.002 and P = 0.001, respectively). This study demonstrates that L1CAM expression status may add prognostic information to endometrial cancer, particularly in the NSMP subgroup. Considering the prognostic importance of L1CAM, its use as a marker may make significant contributions to reducing prognostic heterogeneity, especially in the NSMP subgroup.