Tumour Histology and Primary Site but Not MDM2 Amplification Levels Are Prognostic for Clinical Outcomes in Well Differentiated and Dedifferentiated Liposarcoma

Background:MDM2, an oncogene and p53 inhibitor is consistently amplified in well differentiated (WD) and dedifferentiated (DD) liposarcomas (LPS). Although previous reports have deemed fluorescent in situ hybridization (FISH) of MDM2 as the diagnostic gold standard for WD/DDLPS, the prognostic utility of this biomarker is less well established. This study aims to examine MDM2 amplification as a prognostic factor in LPS. Methods: A retrospective review of clinical records was done to identify patients (pts) with primary LPS that were curatively resected and assessed for MDM2 via FISH. Dual color MDM2/CEP 12 probes were applied to FFPE tissue sections. Signals from 60 non–overlapping nuclei were counted for copy numbers of MDM2 and CEP 12. MDM2 gene amplification was defined as the ratio of MDM2 signals to CEP 12 signals. Receiver operating curve analysis was used to determine a cut-off for high MDM2 ratio (>9.1). Progression free survival (PFS) was assessed from time of resection to relapse or death. Survival analysis was done using Kaplan-Meier and multivariable cox models. Results: 55 pts consisting of 20 DDLPS and 35 WDLPS were identified. Higher levels of MDM2 ratio was associated with retroperitoneal tumour site (8.1 vs 5.4, Mann-Whitney; p=0.023). No statistical difference in MDM2 ratio was seen in other clinical features; including age of diagnosis, performance status, resection margins, tumour histology and size. On univariate survival analysis, DDLPS (HR 11.163; 95%CI 3.935-31.663; p<0.001), positive resection margins (HR 3.138; 95%CI 1.21-8.110; p=0.034) and retroperitoneal primary (HR 6.884; 95%CI 2.324-20.387; p<0.001) were predictive of poorer PFS. However, MDM2 amplification level was not prognostic for PFS (HR 2.191; 95%CI 0.599-8.016; p=0.130). On multivariable analysis, only retroperitoneal primary (HR 3.400; 95%CI 1.015-11.388; p=0.047) and DDLPS (HR 6.993; 95%CI 1.762-27.757, p=0.006) remain prognostic for worse outcomes. Conclusions: In this cohort of WD and DD LPS pts, tumour histology and primary site but not MDM2 amplification level, were prognostic for clinical outcomes. Legal entity responsible for the study: SingHealth Centralised Institutional Review Board Funding: None Disclosure: All authors have declared no conflicts of interest.