The expression of MDM2/CDK4 gene product in the differential diagnosis of well differentiated liposarcoma and large deep-seated lipoma

Ordinary lipomas are cytogenetically characterized by a variety of balanced rearrangements involving chromosome segment 12q13-15, whereas well differe ntiated liposarcomas (WDL) show supernumerary ring and giant marker chromos omes, known to contain amplified 12q sequences. The tight correlation betwe en the presence of ring chromosomes and both amplification and overexpressi on of MDM2 and CDK4 genes suggests the exploration of the possibility that immunocytochemistry (ICC) might assist in the differential diagnosis of lip oma-like well differentiated liposarcomas (LL-WDL) and large deep-seated li pomas (LDSL). For this purpose, 21 cases of the former and 19 cases of the latter tumours were analysed by ICC and, according to the availability of m aterial, by molecular and cytogenetic approaches. All lipomas displayed a n ull MDM2/CDK4 phenotype, whereas all LL-WDL showed MDM2/CDK4 or CDK4 phenot ypes. Southern blot analysis performed on 16 suitable cases, complemented b y fluorescence in situ hybridization and classical cytogenetic analysis in 11 cases, was consistent with, and further supported the immunophenotyping data. In conclusion, MDM2/CDK4 product-based immunophenotyping appears to r epresent a valuable method for the categorization of arguable LDSL. (C) 200 0 Cancer Research Campaign.