Abstract 474: Extracellular vesicle - MDM2 as liquid biopsy biomarker for disease identification in retroperitoneal liposarcoma
Authors: Casadei Lucia , Sarchet Patricia , Cascione Luciano , Nigita Giovanni , de Faria Fernanda Costas Casal , Croce Carlo Maria , Grignol Valerie , Pollock Raphael E. 
Published: July 2021

Introduction: Extracellular vesicles (EVs) are membrane vesicles containing proteins and nucleic acids that aresecreted by all cells and circulate in the blood. In the tumor microenvironment their contents havebeen shown to carry important pro-carcinogenic molecules. Soft tissue sarcoma of theretroperitoneum of which the most common types are well differentiated/dedifferentiatedliposarcoma (WD/DDLPS) are marked by recurrence rates of &gt;50% even after complete resection.A molecular hallmark of RLS WD/DDLPS are high levels of MDM2 DNA, a finding observed innearly all WD/DDLPS tumors. Indeed, FISH assessment of MDM2 in resected tissues is currentlythe definitive diagnostic methodology for WD/DDLPS. Prognosis in WD/DDLPS is enhanced byearly detection of recurrent lesions. However, current scanning technologies cannot resolverecurrent liposarcoma vs postoperative scarring in many patients (97% sensitivity/51%specificity); the need for easily retrieved and analyzed circulating factors that are diagnostic andprognostic is urgent.

Methods: A cohort of 11 WD/DDLPS serum samples were collected at the time of surgery and during followup visits (6-12 months after surgery). Serum from normal healthy people (N=15) were used as acontrol. EVs were isolated from the serum through precipitation technology (ExoQuick) andultracentrifugation. The EVs-DNA was then isolated and the level of MDM2 was measured by Q-PCR. The level of MDM2 DNA in the WD/DDLPS tissues was also measured by Q-PCR andcompared with Normal Adjacent tissues.

Results: MDM2 DNA was detected in EVs of the serum of RLS WD/DDLPS patients at significantly higherlevels than normal controls (geometric mean MDM2 DNA number of molecules value=74,434 vs10,146, p=0.0025). This increase was concordant with the level of MDM2 DNA as measured inWD/DDLPS tissues compared to normal adjacent tissues (p= 0.0009). Moreover, serumWD/DDLPS EV MDM2 was dramatically decreased in RLS WD/DDLPS patients after tumorresection (geometric mean MDM2 DNA number of molecules value pre-op=74,434 vs post-op=13,879, p=0.0048), and appears to correlate with CT-scan evidence of recurrent or persistentdisease after surgery. Importantly, the level of MDM2 DNA in EV's post-operatively decreasedreaching a level similar to the level of MDM2 in the controls (difference between post- surgeryand controls: p=0.47).

Conclusion: In conclusion RLS WD/DDLPS EVMDM2 may potentially serve as an efficacious RLSWD/DDLPS first-ever prognostic and therapy predictive biomarker for a lethal disease currentlylacking such determinants.

Citation Format: Lucia Casadei, Patricia Sarchet, Luciano Cascione, Giovanni Nigita, Fernanda Costas Casal de Faria, Carlo Maria Croce, Valerie Grignol, Raphael E. Pollock. Extracellular vesicle - MDM2 as liquid biopsy biomarker for disease identification in retroperitoneal liposarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 474.