Carboxypeptidase M: a biomarker for the discrimination of well-differentiated liposarcoma from lipoma.
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.
Erickson-Johnson
Michele R
MR
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA.
Seys
Amber R
AR
Roth
Christopher W
CW
King
Allison A
AA
Hulshizer
Rachael L
RL
Wang
Xiaoke
X
Asmann
Yan W
YW
Lloyd
Ricardo V
RV
Jacob
Eapen K
EK
Oliveira
Andre M
AM
D014408:Biomarkers, Tumor / Q000235:genetics*; D002454:Cell Differentiation; D055028:Comparative Genomic Hybridization; D003937:Diagnosis, Differential; D058851:GPI-Linked Proteins; D005784:Gene Amplification; D018628:Gene Dosage; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D005820:Genetic Testing; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008067:Lipoma / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D008080:Liposarcoma / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D008666:Metalloendopeptidases / Q000235:genetics*; D011237:Predictive Value of Tests; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics
D014408:Biomarkers, Tumor; D058851:GPI-Linked Proteins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; C058479:carboxypeptidase M; D008666:Metalloendopeptidases