Atypical Lipomatous Tumor/Well-Differentiated Liposarcoma

Novel Therapeutic Insights in Dedifferentiated Liposarcoma: A Role for FGFR and MDM2 Dual Targeting

“…The first series, analyzed at the protein level, included 418 WDLPS/DDLPS cases from 358 patients enrolled in the FILIPO (NCT03303885, ) multicentric study that involved three French sites (Centre Hospitalier Universitaire of Nice, Nice; Institut Bergonié, Bordeaux, and Centre Antoine Lacassagne, Nice), including 106 patients with WDLPS and 252 patients with DDLPS. All cases were diagnosed by pathologist experts in soft tissue and confirmed by detection of MDM2 amplification, according to the WHO Classification of Soft Tissue and Bone Tumors [ 1 , 2 ]. Clinical, pathological, and follow-up data were available for all patients.…”

“…Among them, liposarcomas (LPS), derived from a lipogenic origin, are divided into four subtypes, according to the World Health Organization (WHO) Classification: atypical lipomatous tumor (ALT)/well-differentiated LPS (WDLPS), dedifferentiated LPS (DDLPS), myxoid LPS, and pleomorphic LPS. ALT/WDLPS are only locally aggressive, but, in 10% of the cases, they recur and dedifferentiate and therefore may acquire the same metastatic potential and poor prognosis as de novo DDLPS [ 1 , 2 ]. Even though the “LPS” subtype has been identified as a favorable prognostic factor in advanced soft tissue sarcomas [ 3 ], and, although new cytotoxic agents have been developed such as trabectedin [ 4 ] and eribulin [ 5 ], the currently available chemotherapy regimens remain poorly efficient in advanced WDLPS/DDLPS [ 6 ].…”

“…With respect to targeted therapies, the pazopanib anti-angiogenic drug represents the only targeted therapy currently approved in soft tissue sarcomas but is not indicated in LPS because of unproven efficiency in the PALETTE trial [ 7 ]. Both WDLPS and DDLPS are characterized by the amplification of a discontinuous region on the long arm of the chromosome 12 [ 1 , 2 ]. This 12q13–15 amplicon encompasses several oncogenes including MDM2 , CDK4 , and HMGA2 [ 1 , 2 , 8 , 9 , 10 ], as well as CPM ( Carboxypeptidase M ), a putative oncogene involved in the EGFR pathway [ 11 ] thus retained as potential therapeutic targets.…”

“…Both WDLPS and DDLPS are characterized by the amplification of a discontinuous region on the long arm of the chromosome 12 [ 1 , 2 ]. This 12q13–15 amplicon encompasses several oncogenes including MDM2 , CDK4 , and HMGA2 [ 1 , 2 , 8 , 9 , 10 ], as well as CPM ( Carboxypeptidase M ), a putative oncogene involved in the EGFR pathway [ 11 ] thus retained as potential therapeutic targets. The discovery of the MDM2 amplification in 100% of WDLPS and DDLPS cases [ 9 ] led to the development of targeted therapies able to restore the pro-apoptotic effect of p53, by inhibiting the MDM2-p53 binding [ 12 , 13 ] including the nutlins.…”

Retroperitoneal Sarcomas: An Update on the Diagnostic Pathology Approach

“…Atypical lipomatous tumor (ALT)/well-differentiated liposarcoma (WDLPS) is a locally aggressive but not metastasizing mesenchymal neoplasm composed either entirely or partly of adipocytic proliferation, showing at least focal nuclear atypia in both adipocytes and stromal cells [ 33 ]. ALT/WDLPS accounts for approximately 40–45% of all liposarcomas.…”