title: Are peripheral purely undifferentiated pleomorphic sarcomas with MDM2 amplification dedifferentiated liposarcomas?
abstract: Dedifferentiated liposarcoma (DDLPS) has been defined as a tumor composed of well-differentiated liposarcoma associated with a nonlipogenic undifferentiated sarcoma and is genetically characterized by a 12q13-15 amplicon with MDM2 amplification. Some peripheral (extremities, trunk wall, head/neck) undifferentiated pleomorphic sarcomas (UPS) without areas of well-differentiated liposarcoma present an MDM2 amplification. We addressed whether they are true DDLPS or not. We compared the clinical data, histologic data, MDM2 status (immunohistochemistry [IHC], fluorescence in situ hybridization [FISH]), genomic profile (array comparative genomic hybridization), and follow-up of 19 patients with peripheral UPS with MDM2 amplification and 62 with peripheral conventional DDLPS retrieved from the French sarcoma network (RRePS) and the Conticabase (Connective Tissue Cancer Network database). For a control cohort, we described 153 patients from the Conticabase, with peripheral UPS without expression of MDM2 by IHC. By IHC, tumor cells were positive for MDM2 in 59 conventional DDLPS and in all UPS with MDM2 amplification. FISH analysis and/or quantitative polymerase chain reaction showed amplification of MDM2 in 54 conventional DDLPS and in all UPS with MDM2 amplification. The 2-year overall survival rates of UPS with MDM2 amplification, conventional DDLPS, and UPS without expression of MDM2 were 93.3%, 90.7%, and 73.9%, respectively. Such similarities in the clinical characteristics, morphology, genomic profile, and follow-up of peripheral UPS with MDM2 amplification and peripheral conventional DDLPS strongly suggest that peripheral UPS with MDM2 amplification are in fact DDLPS. Faced with histologic diagnosis of UPS, a systematic IHC evaluation of MDM2 allows a selection of cases for FISH analysis permitting the diagnosis of DDLPS.
authors: Departments of *Pathology ‡Biostatistics, Institut Claudius Regaud, Toulouse †Department of Pathology and INSERM U916, Institut Bergonié **University Bordeaux Ségalen, Bordeaux §Department of Pathology, Centre Léon Bérard, Lyon ∥Department of Pathology, Centre Oscar Lambret, Lille ¶Department of Pathology, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, Sorbonne Paris Cité #Department of Pathology, Institut Gustave Roussy, Paris, France.
authors: Sophie
authors: S
authors: Le Guellec
authors: Frédéric
authors: F
authors: Chibon
authors: Monia
authors: M
authors: Ouali
authors: Gaëlle
authors: G
authors: Perot
authors: Anne-Valérie
authors: AV
authors: Decouvelaere
authors: Yves-Marie
authors: YM
authors: Robin
authors: Frédérique
authors: F
authors: Larousserie
authors: Philippe
authors: P
authors: Terrier
authors: Jean-Michel
authors: JM
authors: Coindre
authors: Agnès
authors: A
authors: Neuville
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D054337:Cell Dedifferentiation; D002454:Cell Differentiation; D003937:Diagnosis, Differential; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005784:Gene Amplification; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008080:Liposarcoma / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011237:Predictive Value of Tests; D051736:Proto-Oncogene Proteins c-mdm2 / Q000032:analysis* / Q000235:genetics; D012189:Retrospective Studies; D012509:Sarcoma / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000401:mortality / Q000473:pathology; D009626:Terminology as Topic; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2