title: Liposarcomatous differentiation in malignant phyllodes tumours is unassociated with MDM2 or CDK4 amplification.
abstract: OBJECTIVE
  Breast sarcomas are rare, usually occurring in the setting of malignant phyllodes tumour (MPT). Heterologous differentiation commonly resembles well-differentiated or pleomorphic liposarcoma. In extramammary sites, these subtypes have different biological behaviours and distinct genetic alterations: MDM2 and CDK4 amplification in well-differentiated liposarcoma, and polyploidy with complex structural rearrangements in pleomorphic liposarcoma. The aim of this study was to investigate foci resembling well-differentiated liposarcoma in MPT for MDM2 and CDK4 amplification.
  
  
  RESULTS
  We evaluated the clinicopathological characteristics of MPTs received by the Vanderbilt Breast Consultation Service containing components resembling well-differentiated or pleomorphic liposarcoma. Cases with available tissue blocks were subjected to fluorescence in-situ hybridization with MDM2 and CDK4 probes. Thirty-eight MPTs with liposarcomatous components were available for review. The mean patient age was 49.8 years (range 26-84 years). In addition to well-differentiated liposarcoma, the following components were also present: high-grade undifferentiated sarcoma (n = 9; 23.7%), pleomorphic liposarcoma (n = 4; 10.5%), non-high-grade sarcoma not otherwise specified (n = 22; 57.9%), and malignant peripheral nerve sheath tumour-like (n = 2; 5.2%). Among 10 cases tested, none showed amplification of MDM2 or CDK4.
  
  
  CONCLUSIONS
  This study examined molecular changes in the well-differentiated liposarcomatous components of MPT. Despite histological similarity to well-differentiated liposarcoma of soft tissues, liposarcomatous differentiation in MPT lacks the molecular phenotype characteristic of extramammary well-differentiated liposarcoma.
authors.affiliation: Department of Pathology, Bay Pines VA Health Care System, St Petersburg, FL, USA.
authors.forename: Pamela L
authors.initials: PL
authors.lastname: Lyle
authors.affiliation: Departments of Pathology and Microbiology, Pediatrics and Orthopaedic Surgery, Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Julia A
authors.initials: JA
authors.lastname: Bridge
authors.affiliation: Breast Pathology Consultants, Inc., Nashville, TN, USA.
authors.forename: Jean F
authors.initials: JF
authors.lastname: Simpson
authors.affiliation: Department of Pathology, Immunology and Microbiology, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Justin M
authors.initials: JM
authors.lastname: Cates
authors.affiliation: Department of Pathology, Immunology and Microbiology, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Melinda E
authors.initials: ME
authors.lastname: Sanders
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D002454:Cell Differentiation; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008080:Liposarcoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D018317:Nerve Sheath Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D010641:Phenotype; D003557:Phyllodes Tumor / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4
keywords: CDK4; MDM2; liposarcoma; liposarcomatous differentiation; malignant phyllodes tumour