Four years later in a second examination with molecular methods for a study of adrenal sarcomas, this diagnosis must be revised due to the lack of MDM-2 gene amplification and FKHR translocation which exclude sarcoma.
In line with this, sarcomas with MDM2-negative rings commonly show complete loss of either CDKN2A or RB1 -both known to be important for genome integrity.
In this study, we have assessed the occurrence of p53, Rb and MDM2 alterations in the same samples of osteosarcomas, along with representative samples of various other sarcomas.
A constitutional G allele has also been associated with earlier onset of various cancer types, and studies of sarcomas have shown an enrichment of the G allele in tumors with MDM2 amplification, notably atypical lipomatous tumor (also known as well-differentiated liposarcoma).
For MDM2T309G variant, pooled results from the meta-analysis indicate that carriers of TG and GG genotypes showed a 34% increased risk to develop sarcomas compared to TT carriers.
Our knowledge of the molecular biology of sarcomas has progressed considerably over the past year, with major emphasis on the role of p53 and MDM2 gene mutations.
Many malignancies display amplification of MDM genes encoding negative regulators of p53 and therefore much effort to date has concentrated on the development of molecules that inhibit MDM2, the most advanced of which are being tested in clinical trials for sarcoma, glioblastoma, bladder cancer and lung adenocarcinoma.
We compared sensitivity and specificity of p16 IHC to MDM2 and CDK4 IHC in the differential diagnosis of ALT-WDLPS (n=19) versus benign adipocytic tumors (n=44) and DDLPS (n=18) versus mimicking sarcomas (n=20).
We propose, therefore, that MDM2 markers along with TP53 sequencing should be considered as patient biomarkers in clinical trials of sarcomas using MDM2 antagonists.
Although MDM2 is almost always positive in well-differentiated liposarcoma, which is useful in differentiating benign from atypical/well-differentiated lipomatous tumor, it should not be used in differentiating liposarcoma from other sarcomas.
We compared the clinical data, histologic data, MDM2 status (immunohistochemistry [IHC], fluorescence in situ hybridization [FISH]), genomic profile (array comparative genomic hybridization), and follow-up of 19 patients with peripheral UPS with MDM2 amplification and 62 with peripheral conventional DDLPS retrieved from the French sarcoma network (RRePS) and the Conticabase (Connective Tissue Cancer Network database).