Well-differentiated liposarcoma/
atypical lipomatous tumor and
dedifferentiated liposarcoma can be difficult to distinguish from benign lipomatous
neoplasms and other high-grade
sarcomas, respectively. Cytogenetics in these
tumors has identified ring and giant chromosomes composed of 12q13-15 amplicons including the MDM2 gene. Identifying MDM2 amplification by fluorescence in situ hybridization may prove an adjunctive tool in the diagnosis of lipomatous
neoplasms. Dual color fluorescence in situ hybridization employing a laboratory-developed BAC label probe cocktail specific for MDM2 (12q15) and a probe for the centromeric region of chromosome 12 (Abbott Molecular, DesPlaines, IL) was performed on
formalin-fixed and
paraffin-embedded tissue including whole sections from
atypical lipomatous tumors (n=13),
dedifferentiated liposarcomas (n=14), benign lipomatous
tumors (
n=30), and pleomorphic
sarcoma, not otherwise specified (n=10), and a tissue microarray containing a variety of high-grade
sarcomas (n=63). An MDM2/chromosome 12 ratio >or=2.0 was considered amplified, <2.0 nonamplified, and cases displaying >2 signals of both probes and an MDM2 ratio <2.0 polysomic for chromosome 12. Of the well-differentiated and
dedifferentiated liposarcomas, 100% showed amplification of MDM2. Chromosome 12 polysomy was noted in 89% of spindle cell/
pleomorphic lipomas, while all
angiolipomas and
lipomas were nonamplified and eusomic. MDM2 amplification was observed in 40% of pleomorphic
sarcomas and a small subset of high-grade
sarcomas (3/63). MDM2/chromosome 12 fluorescence in situ hybridization is a sensitive and specific tool (both 100%) in evaluating low-grade lipomatous
neoplasms. The specificity decreases in high-grade
sarcomas, as MDM2 amplification was observed in a small portion of pleomorphic
sarcomas and high-grade
sarcomas other than
dedifferentiated liposarcomas. Importantly, none of the benign lipomatous lesions were MDM2 amplified and even cells in areas of
well-differentiated liposarcomas with minimal cytologic atypia were amplified, making the probe a valuable tool in the diagnosis of even limited biopsy samples of well-differentiated lipomatous
neoplasms.