Using cross species genomic analysis, we define a geneset from the LSL-Kras(G12D); Trp53(Flox/Flox) mouse model of soft tissue sarcoma that is highly enriched in human MFH.
Abnormalities identified by immunohistochemistry included p21 immunonegativity (60%, 25%, 93%), which was most frequent in TE-GBM (P = .008), strong nuclear p53 staining (29%, 29%, 41%), strong membranous staining for epidermal growth factor receptor (EGFR) (21%, 63%, 19%), which was most frequent in E-GBM (P = .03), and an increased frequency of p27 immunonegativity in gliosarcomas (15% negative, 85% focal) compared with tumors without sarcoma (38% strongly positive) (P = .009).
Soft tissue sarcoma patients with the Pro/Pro variant had a reduced survival rate (30%), when compared to the p53 Arg/Arg (45%) and the p53 Arg/Pro groups (55%).
Germline TP53 mutations predispose to a rare familial cancer syndrome, the Li-Fraumeni Syndrome (LFS), characterized by the early onset of multiple cancers including childhood adrenocortical carcinomas, sarcomas and brain tumors, and breast and colon cancer in young adults.
The mechanism responsible for tumour regression is dependent on the tumour type, with the main consequence of p53 restoration being apoptosis in lymphomas and suppression of cell growth with features of cellular senescence in sarcomas.
These data are in support of the following tissue-specific processes: in sporadic breast cancer (sarcomas etc.), loss of methylation sites (in 35 codons mostly next to codon 133), might lead to loss of silencing of TP53 isoforms which are suppressed in these tissues.
The aim of this study was to investigate the expression of proteins that are involved in the p53 pathway and apoptosis in different types of soft tissue sarcomas and to correlate the expression of these proteins with the histologic grade of sarcoma cases.
A high proportion (58%) of the radiation-induced sarcomas exhibited a somatic inactivating mutation for one allele of TP53, systematically associated with a loss of the other allele.