The p53 gene in soft tissue sarcomas : Prognostic value of DNA sequencing versus immunohistochemistry

Background: The aim of this study was to compare sequencing and immunohistochemistry (IHC) for their ability to detect p53 mutations and to assess their prognostic value in soft tissue sarcomas (STS). Material and Methods: 146 STS samples were investigated by single strand DNA conformation polymorphism (SSCP)-sequencing for p53 mutations. Additionally, IHC with five p53 antibodies (CM-1, Pab1801, Pab240, DO1, DO-7) was performed. Results: In 65 to 131 tumor samples (44.5% to 90.4%) elevated levels of p53 protein were recorded by IHC, depending on the antibody applied. Sixteen out of 146 STS tumor samples (11%) had p53 gene mutations. 13 cases (81.2%) of the 16 tumors with p53 mutations could be detected by DO-1. However of the 93 DO-1 positive tumors 79 were negative by SSCP-sequencing analysis. Using multivariate regression analysis (Cox proportional hazards model) both p53 mutations (non-frameshift mutations) and IHC detection of p53 protein overexpression were prognostic predictors for poor survival. Conclusions: This study suggests that IHC is valuable for assessing p53 mutations in STS, but sequencing provides additional important information on the molecular characteristics of the alterations.