Dedifferentiation of a well-differentiated liposarcoma to a highly malignant metastatic osteosarcoma: amplification of 12q14 at all stages and gain of 1q22-q24 associated with metastases

Well-differentiated liposarcomas (WDLPS), especially those located in the r etroperitoneum, may occasionally undergo dedifferentiation. Although this p rocess is associated with a more aggressive clinical course, dedifferentiat ed liposarcomas rarely produces metastases. The case reported here is rathe r uncommon: A retroperitoneal WDLPS gave lung metastases that were diagnose d as highly malignant osteosarcomas. We used comparative genomic hybridizat ion (CGH), fluorescence in situ hybridization (FISH), and Southern blot ana lyses to characterize the copy number changes and genetic aberrations occur ring at different stages of the disease. In the primary tumor, the only det ectable aberration was amplification of 12q13-q14, which was present only i n a fraction of the cells and revealed by FISH analysis. High-level amplifi cation of 12q13-q14, involving CDK4, MDM2, and HMGIC, was seen both in the relapse and the metastases, The second most common change, gain or high-lev el amplification of 1q22-q24, was detectable by CGH only in the osteogenic metastases, as was loss of the distal 2q. FISH analyses revealed considerab le heterogeneity in the samples, and the percentage of cells showing aberra tions was significantly higher in the metastatic samples. In particular, in creased copy numbers of 789f2, a marker for 1q21 amplification in sarcomas, was observed in more than 65% of the cells in the metastatic samples, but in less than 10% of the cells from the recurrent samples. These observation s could indicate that Iq amplification, in particular, may be indicative of a more malignant phenotype and ability of metastasis in WDLPS, as has also been suggested by others. (C) 2001 Elsevier Science, Inc. Ah rights reserv ed.