CPM, 12q15, for Well-Differentiated Liposarcoma/Atypical Lipomatous Tumor, FISH
Supporting a diagnosis of well-differentiated liposarcoma/atypical lipomatous tumor
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
The histological discrimination of well-differentiated liposarcoma/atypical lipomatous tumor (WDL/ALT) from lipoma can be diagnostically challenging. However, standard cytogenetic identification of ring and giant rod chromosomes strongly support the diagnosis of WDL/ALT. These abnormal chromosomes are mainly composed of amplified sequences derived from chromosome bands 12q13-15, and contain several amplified genes including MDM2, CPM, CDK4, and TSPAN31. MDM2 is amplified in >99% of WDL, and up to 30% of other types of sarcomas. The CPM gene encodes carboxypeptidase M, a membrane-bound arginine/lysine carboxypeptidase. CPM is located only 11 kb upstream from MDM2, and is consistently coamplified with MDM2 in WDL/ALT.(1) Similar to MDM2, this gene has been observed to be amplified in virtually all cases of WDL/ALT, but not in lipomas.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
0-9% amplified cells
An interpretive report will be provided.
A neoplastic clone is detected when the percent of cells with an abnormality exceeds the normal reference range for the CPM FISH probe (positive result).
A positive result is consistent with amplification of the CPM gene locus on 12q13-15 and supports the diagnosis of well-differentiated liposarcoma/atypical lipomatous tumor (WDL/ALT).
A negative result is consistent with absence of amplification of the CPM gene locus on 12q13-15. However, negative results do not exclude the diagnosis of WDL/ALT. Amplification varies in individual tumors and among different cells in the same tumor.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Reliable results are dependent on adequate specimen collection and processing. This test has been validated on formalin-fixed, paraffin-embedded tissue; other types of fixatives are discouraged. Improper treatment of tissues, such as decalcification, may cause FISH failure.
Clinical diagnosis and/or therapy should not be based solely on this assay. The results should be considered in conjunction with clinical information and/or additional diagnostic tests.
Initial Mayo investigations on more than 200 lipomatous tumors demonstrated that CPM is coamplified with MDM2 in 100% of cases. A posterior blinded validation study was performed on 61 formalin-fixed, paraffin-embedded tissues including 19 liposarcoma tumors, 20 lipoma tumors, and 22 other tumors. Each specimen had been previously characterized by 2 soft tissue pathologists. Two technologists scored 100 interphase nuclei for each specimen (200 total cells/case). Results showed that 19 of the 19 well-differentiated liposarcoma/atypical lipomatous tumors (WDL/ALT) had amplification of CPM. Each of the 42 nonlipomatous and lipoma tumors yielded normal results (ie, negative for both rearrangement and amplification).
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Erickson-Johnson MR, Seys AR, Roth CW, et al: Carboxypeptidase M: a biomarker for the discrimination of lipoma from liposarcoma. Mod Pathol 2009 Dec;22(12):1541-1547
2. Jacob E, Erickson-Johnson MR, Wang X, et al: Assessment of MDM2 amplification using fluorescence in situ hybridization on paraffin-embedded tissue discriminates atypical lipomatous tumors from lipomas. Mod Pathol 2006;19:13A