Carboxypeptidase M: a biomarker for the discrimination of well-differentiated liposarcoma from lipoma

Mod Pathol. 2009 Dec;22(12):1541-7. doi: 10.1038/modpathol.2009.149. Epub 2009 Oct 9.


The discrimination between well-differentiated liposarcomas/atypical lipomatous tumors and lipomas can be diagnostically challenging at the histological level. However, cytogenetic identification of ring and giant rod chromosomes supports the diagnosis of well-differentiated liposarcoma/atypical lipomatous tumor. These abnormal chromosomes are mainly composed of amplified genomic sequences derived from chromosome 12q13-15, and contain several genes, including MDM2, CDK4 (SAS), TSPAN31, HMGA2, and others. MDM2 is consistently amplified in well-differentiated liposarcomas/atypical lipomatous tumors, and up to 25% in other sarcomas. As part of a large genomic study of lipomatous neoplasms, we initially found CPM to be consistently amplified in well-differentiated liposarcomas/atypical lipomatous tumors. To further explore this initial finding, we investigated the copy number status of MDM2 and CPM by fluorescent in situ hybridization (FISH) on a series of 138 tumors and 17 normal tissues, including 32 well-differentiated liposarcoma/atypical lipomatous tumors, 63 lipomas, 11 pleomorphic lipomas, 2 lipoblastomas, 30 other tumors and 17 normal fat samples. All 32 well-differentiated liposarcoma/atypical lipomatous tumors showed amplification of MDM2 and CPM, usually >20 copies per cell. The other tumors lacked MDM2 and/or CPM amplification. Chromogenic in situ hybridization confirmed the above results on a subset of these tumors (n=27). These findings suggest that identification of CPM amplification could be used as an alternative diagnostic tool for the diagnosis of well-differentiated liposarcoma/atypical lipomatous tumors.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Cell Differentiation*
  • Comparative Genomic Hybridization
  • Diagnosis, Differential
  • GPI-Linked Proteins
  • Gene Amplification*
  • Gene Dosage
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Genetic Testing
  • Humans
  • In Situ Hybridization, Fluorescence
  • Lipoma / diagnosis*
  • Lipoma / enzymology
  • Lipoma / genetics
  • Lipoma / pathology
  • Liposarcoma / diagnosis*
  • Liposarcoma / enzymology
  • Liposarcoma / genetics
  • Liposarcoma / pathology
  • Metalloendopeptidases / genetics*
  • Predictive Value of Tests
  • Proto-Oncogene Proteins c-mdm2 / genetics


  • Biomarkers, Tumor
  • GPI-Linked Proteins
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2
  • carboxypeptidase M
  • Metalloendopeptidases