MDM2 gene amplification in bone and soft‐tissue tumors: Association with tumor progression in differentiated adipose‐tissue tumors

We have studied 107 bone and soft‐tissue sarcomas and 8 lipomas for amplification of the MDM2 gene. This gene was amplified in 3 out of 67 osteosarcomas, 3 out of 20 malignant fibrous histiocytomas, 4 out of 20 liposarcomas, and 4 out of 8 lipomas. The amplification was associated with overexpression of mRNA. In osteosarcomas, contrary to previous findings, all amplifications were observed in primary lesions. In liposarcomas, the amplification was seen exclusively in well‐differentiated tumors with high frequency (4/5) but not in other subtypes (0/15). In addition, MDM2 amplification was also frequently found in deep‐seated intra‐ or intermuscular lipomas (4/5). Hence, it is suggested that MDM2 amplification plays a significant role in the development of differentiated adipose‐tissue tumors. Three well‐differentiated liposarcomas with MDM2 amplification coexisted with high‐grade dedifferentiated sarcomas, in which MDM2 amplification was also observed. Interestingly, in 2 of these cases, the grades of amplification correlated with the histological grades, indicating an important role of MDM2 overexpression in tumor progression. © 1995 Wiley‐Liss, Inc.

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