Analysis of p53 and mdm2 proteins in malignant fibrous histiocytoma in absence of gene alteration: prognostic significance

TP53 and MDM2 genes and their protein expression were evaluated in frozen a nd paraffin-embedded tissue from 27 patients with malignant fibrous histioc ytoma to elucidate the relationship between them, their implication in tumo r progression mechanisms and their possible diagnostic-prognostic value in malignant fibrous histiocytoma. Single-strand conformation polymorphism ana lysis and direct sequencing of polymerase chain reaction-amplified DNA were used to establish two TP53 mutations (7.4%): a point mutation and a 63-bp duplication. Amplification of the MDM2 gene was observed in two tumors (7.4 %) by means of Southern-blot analysis, one of them also carrying the TP53 p oint mutation. Immunohistochemical and Western-blot techniques were used to study nuclear accumulation of p53 and mdm2 proteins: 11 cases (40.7%) with p53 protein expression and thirteen cases (48.1%) with mdm2 protein expres sion were detected. We confirmed overexpression of mdm2 protein in eight of ten cases (80%) with p53 protein expression without TP53 gene mutation. St atistical analysis shows that simultaneous co-expression of p53 and mdm2 in malignant fibrous histiocytoma is significantly correlated with survival i n absence of gene alteration in contrast to the lack of statistical correla tion with survival of p53 protein expression alone.