title: High level of CDK4 amplification is a poor prognostic factor in well-differentiated and dedifferentiated liposarcoma.
abstract: The amplification of MDM2 and CDK4 is the main molecular feature of well-differentiated liposarcomas (WDLS) and dedifferentiated liposarcomas (DDLS). Although the diagnostic usefulness of this molecular characteristic in liposarcomas has been investigated, its prognostic utility of quantitative gene level has not been explored. The aim of this study was to assess the prognostic significance of level of CDK4 amplification in MDM2-amplified WDLS/DDLS. MDM2 amplification in liposarcomas was confirmed by fluorescence in situ hybridization. The copy number of MDM2 and CDK4 was further determined by quantitative PCR (qPCR) and multiplex ligation-dependent probe amplification. Among 56 MDM2-amplified liposarcomas, 30 cases were assigned as WDLS, and 26 as DDLS. When liposarcomas were classified by qPCR-determined CDK4 amplification levels, the high-CDK4 group showed significantly poorer progression free survival (P=0.001) and disease specific survival (P=0.033) than the low-CDK4 group. However, MDM2 amplification level did not show prognostic significance. In WDLS/DDLS, the level of CDK4 amplification was useful for prognosis prediction and precise stratification of patients for targeted therapy.
authors.affiliation: Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Seung Eun
authors.initials: SE
authors.lastname: Lee
authors.affiliation: Laboratory of Cancer Genomics and Molecular Pathology, Samsung BioResearch Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Yu Jin
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Kyungpook National University, Daegu, and Research Institute of Pharmaceutical Sciences, College of Pharmacy, Kyungpook National University, Daegu, Korea.
authors.forename: Mi Jeong
authors.initials: MJ
authors.lastname: Kwon
authors.affiliation: Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Dong Ill
authors.initials: DI
authors.lastname: Choi
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jeeyun
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Junhun
authors.initials: J
authors.lastname: Cho
authors.affiliation: Department of Orthopedic Surgery, Samsung Medical Center, and Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Sung Wook
authors.initials: SW
authors.lastname: Seo
authors.affiliation: Samsung Advanced Institute for Health Sciences & Technology, and Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Sung Joo
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Laboratory of Molecular Pathology and Cancer Genomics, Department of Pharmacy, College of Pharmacy, Seoul National University.
authors.forename: Young Kee
authors.initials: YK
authors.lastname: Shin
authors.affiliation: Department of Pathology, Samsung Medical Center, Laboratory of Cancer Genomics and Molecular Pathology, Samsung BioResearch Institute, Samsung Medical Center, and Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University School of Medicine, Seoul, Korea. ylachoi@skku.edu.
authors.forename: Yoon-La
authors.initials: YL
authors.lastname: Choi
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D005784:Gene Amplification; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008080:Liposarcoma / Q000235:genetics* / Q000401:mortality* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D060885:Multiplex Polymerase Chain Reaction; D060787:Neoplasm Grading; D011379:Prognosis; D016016:Proportional Hazards Models; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4