title: Clinical and molecular approaches to well differentiated and dedifferentiated liposarcoma.
abstract: OBJECTIVE
  Liposarcoma, a rare disease, is classified into five histologic subtypes. These include well differentiated liposarcoma (WDLS) and dedifferentiated liposarcoma (DDLS), both characterized by chromosome 12q13-15 amplification. This review will focus on the clinical management of WDLS and DDLS and examine recent molecular studies that have the potential to affect clinical management.
  
  
  RESULTS
  Outcome of patients with WDLS and DDLS depends on completeness of surgical resection as well as tumor location and histologic subtype. Risk of recurrence is high for patients with dedifferentiated histology or retroperitoneal location. We now understand that surgical outcomes are poor for patients with rapidly growing or incompletely resectable tumors, so these patients should be managed nonoperatively. Radiation and chemotherapy have low response rates in WDLS and DDLS, but novel agents targeted at chromosome 12 gene products MDM2 and CDK4 have shown promise in preclinical studies and are being tested in clinical trials. Cell line, tissue microarray, and genomic analyses have identified additional targets including ZIC1, TOP2A, AURKA, and IGF-1R, which could form the basis of future therapies.
  
  
  CONCLUSIONS
  Although complete surgical resection is currently the most effective treatment for WDLS and DDLS, the majority of patients with retroperitoneal liposarcoma will eventually have recurrence and die of disease. It is hoped that a multimodality approach, which incorporates targeted therapies and complete surgical resection, will significantly improve patient outcomes.
authors.affiliation: Sarcoma Disease Management Program, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Aimee M
authors.initials: AM
authors.lastname: Crago
authors.forename: Samuel
authors.initials: S
authors.lastname: Singer
mesh_terms: D054337:Cell Dedifferentiation; D002454:Cell Differentiation / Q000235:genetics; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D003131:Combined Modality Therapy; D051358:Cyclin-Dependent Kinase 4 / Q000037:antagonists & inhibitors; D006801:Humans; D008080:Liposarcoma / Q000188:drug therapy / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control / Q000628:therapy; D051736:Proto-Oncogene Proteins c-mdm2 / Q000037:antagonists & inhibitors
chemical_list: C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4