High amplification levels of MDM2 and CDK4 correlate with poor outcome in patients with dedifferentiated liposarcoma: A cytogenomic microarray analysis of 47 cases

Dedifferentiated liposarcoma (DDLS) is characterized at the molecular level by amplification of genes within 12q13-15 including MDM2 and CDK4. However, other than FNCLCC grade, prognostic markers are limited. We aim to identify molecular prognostic markers for DDLS to help risk stratify patients. To this end, we studied 49 cases of DDLS in our institutional archives and performed cytogenomic microarray analysis on 47 cases. Gene copy numbers for 12 loci were evaluated and correlated with outcome data retrieved from our institutional electronic medical records. Using cut point analysis and comparison of Kaplan-Meier survival curves by log rank tests, high amplification levels of MDM2 (>38 copies) and CDK4 (>30 copies) correlated with decreased disease free survival (DFS) (P = .0168 and 0.0169 respectively) and disease specific survival (DSS) (P = .0082 and 0.0140 respectively). Additionally, MDM2 and CDK4 showed evidence of a synergistic effect so that each additional copy of one enhances the effect on prognosis of each additional copy of the other for decreased DFS (P = .0227, 0.1% hazard). High amplification of JUN (>16 copies) also correlated with decreased DFS (P = .0217), but not DSS. The presence of copy number alteration at 3q29 correlated with decreased DSS (P = .0192). The presence of >10 mitoses per 10 high power fields and FNCLCC grade 3 also correlated with decreased DFS (P = .0310 and 0.0254 respectively). MDM2 and CDK4 gene amplification levels, along with JUN amplification and copy alterations at 3q29, can be utilized for predicting outcome in patients with DDLS.