FREQUENT OCCURRENCE OF P53 MUTATIONS IN RHABDOMYOSARCOMA AND LEIOMYOSARCOMA, BUT NOT IN FIBROSARCOMA AND MALIGNANT NEURAL TUMORS

We have analyzed soft-tissue sarcomas (STS) molecularly for mutations in the tumor-suppressor gene p53 and immunohistochemically for express ion of p53 and mdm2 proteins. In this study, tumor samples from 3 grou ps of soft-tissue sarcomas, i.e., fibrosarcomas, myogenic sarcomas and malignant neural tumors (MNT), were investigated. The methods applied encompass immunohistochemistry on 198 tumor samples using p53 antibod ies (DO-1 and DO-7) and an mdm2 antibody (IF-2). Out of these, 100 sam ples were subjected to non-radioactive PCR-SSCP-sequencing analysis. I mmunohistochemical detection rate for p53 (range of 57% to 67%) and fo r mdm2 proteins (range of 19 to 44%) was similar in all 3 groups. In h igher tumor grades, an increased rate of immunopositivity was found fo r p53 but not for mdm2. Investigation of p53 mutational status reveale d 6 mutations in myogenic sarcomas but none in malignant neural tumors or fibrosarcomas, suggesting different roles of p53 in the 3 STS grou ps. Interestingly, a G --> A transition in codon 245 (a CpG site) was found in 3 myogenic sarcomas. Our results and those of others suggest p53 codon 245 as a mutational hotspot in sarcomas, as recognized in ca rcinomas. (C) 1996 Wiley-Liss, Inc.