(P 335) EXTRACELLULAR VESICLE MDM2 DNA AS A BIOMARKER OF TUMOR PRESENCE AND RECURRENCE IN RETROPERITONEAL LIPOSARCOMA

Objective: A hallmark of well-differentiated and de-differentiated (WD/DD) retroperitoneal liposarcoma is elevated MDM2 due to genome amplification and recurrence rates of >50% even after complete resection. Surveillance imaging frequently cannot resolve recurrent WD/DD-RLS versus postoperative scarring. Early detection of recurrent lesions, for which biomarkers are lacking, would enable more timely therapeutic interventions. We sought to assess the levels of MDM2-DNA within extracellular vesicles (EVs) isolated from the serum of retroperitoneal liposarcoma (RLS) patients versus healthy donors, as well as within the same patients at the time of surgery versus post-operative surveillance visits to identify whether EV-MDM2 may serve as a potential biomarker for liposarcoma recurrence.

Methods: WD/DD-RLS serum samples (n=42) were collected both at the time of surgery and during several follow-up visits, along with sera from healthy donors (n=14). EVs were isolated, DNA purified and MDM2-DNA number of molecules (NM) was determined through q-PCR. Wilcoxon rank sum test was employed to compare patient versus control groups, while Wilcoxon signed-rank tests were used to compare MDM2-DNA levels at the time of surgery versus post-surgery conditions.

Results: EV-MDM2 DNA levels were significantly higher in WD/DD-RLS than controls {mean: controls NM=31,213 [log2 = 14.60; SD = 1.00], time of surgery NM=1,265,643 [log2 = 16.66; SD = 2.58]; (p= 0.00085)}. EV-MDM2 DNA levels were remarkably decreased in WD/DD-RLS patients after resection {mean time of surgery, NM=1,265,643 [log2 = 16.66; SD = 2.58]; mean post-surgery, NM=63,225 [log2 = 15.23; SD = 1.56] (p=0.00036)}, reaching values comparable to control group (p=0.124). Longitudinal values were available in a subset of patients (n=10). Five patients did not develop recurrences and values remained low during surveillance visits over a follow-up period of 6-48 months. In 5 patients who did develop recurrence EV-MDM2 DNA values increased at the time of recurrence as coincident with imaging detected recurrence and decreased again post- resection.

Conclusion: Serum EV-MDM2 is able to differentiate the presence of tumor in patients with retroperitoneal liposarcoma and may serve as a potential biomarker of early recurrent or post-operatively persistent WD/DD-RLS, a disease currently lacking such determinants.