MOLECULAR AND IMMUNOHISTOCHEMICAL P53 STATUS IN LIPOSARCOMA AND MALIGNANT FIBROUS HISTIOCYTOMA - IDENTIFICATION OF 7 NEW MUTATIONS FOR SOFT-TISSUE SARCOMAS

Background. p53 mutations are the most frequently observed tumor-relat ed genetic changes. Mutational analysis concerns mostly carcinomas and is not comprehensive for soft tissue sarcomas. Among soft tissue sarc omas, malignant fibrous histiocytoma (MFH) and liposarcoma represent t he most frequent tumor types, Most of the few identified mutations for soft tissue sarcomas are localized in the core domain of p53, A corre lation between p53 positive immunoreactivity, missense mutations, and a poor prognosis is generally assumed. However, the character of p53 m utations and their functional importance for the clinical process is s till unknown. Methods, Sixty-two soft tissue sarcoma samples were inve stigated for the presence of p53 mutations and for p53 immunoreactivit y. Exons 4-9 of the p53 gene were amplified from genomic DNA with the polymerase chain reaction. A prescreen for mutations was performed by nonradioactive single strand conformation polymorphism analysis; strik ing cases were sequenced directly. For an evaluation of the immunohist ochemical status, five p53 antibodies were used. Results. In 10 tumor samples 7 new p53 mutations and one polymorphism were identified. Muta tions were detected for five liposarcomas (four patients) and four MFH s (three patients). Of the seven mutations, three were missense point mutations, three were deletions, and one was a complex conversion. All mutations but one were localized in the core domain of p53, Of 62 tum or samples, 56% (14 of 32 liposarcomas and 21 of 30 MFHs) were positiv e for p53 immunostaining. Conclusions. The mutations identified in the core domain affect codons that are structurally or functionally invol ved in DNA binding. A relation between p53 positive immunoreactivity a nd a poor prognosis, but not with an exclusively high tumor grade, is evident. p53 mutations in soft tissue sarcomas have a similar spectrum to those in carcinomas.