부산대학교 도서관

Simple Summary: Here, we showed the independent prognostic value of the four molecular subgroups—POLE-mutated, MMR-deficient, p53-abnormal, 'no specific molecular profile' (NSMP)—on a cohort of high-risk endometrial cancer patients. L1 neuronal cell adhesion molecule (L1CAM) expression could further stratify the NSMP subgroup, with L1CAM-positive patients having the worst prognosis compared to all other molecular subgroups. All NSMP/L1CAM-positive patients were "early-relapsing", showing a significantly shorter platinum-free interval than L1CAM-negative patients after adjuvant platinum-based chemotherapy. Since the NSMP is the most heterogeneous subgroup, we believe that L1CAM may represent a relevant candidate biomarker to complement both prognostic stratification and prediction of chemotherapy benefit in patients with high-risk endometrial cancer. Histopathologic assessment of high-risk endometrial cancer (EC) suffers from intersubject variability and poor reproducibility. The pragmatic classification in four molecular subgroups helps to overcome these limits, showing a significant prognostic value. The "no specific molecular profile" (NSMP) is the most heterogeneous EC subgroup, requiring further characterization to better guide its clinical management. DNA sequencing of POLE exonuclease domain and immunohistochemistry for PMS2, MSH6, and p53 were performed in order to stratify a cohort of 94 high-risk EC patients in the four molecular subgroups. Moreover, a panel of seven additional biomarkers was tested. Patients were found to be 16% POLE-mutated, 36% mismatch repair-deficient, 27% p53-abnormal, and 21% NSMP. In the multivariable model, molecular groups confirmed their significant association with disease-specific survival and progression-free survival, with p53-abnormal and NSMP endometrial cancer characterized by poor outcomes. Among the additional evaluated biomarkers, L1CAM was the only one with a significant prognostic value within the NSMP subgroup. NSMP/L1CAM-positive patients experienced the worst outcome and were "early-relapsing" after platinum-based chemotherapy, with a significantly shorter platinum-free interval compared to L1CAM-negative patients. L1CAM appears to be a promising candidate as a prognostic and predictive biomarker in the high-risk NSMP subgroup, which is actually known to lack specific molecular markers. [ABSTRACT FROM AUTHOR]