Prognostic significance of p53 gene mutations and p53 protein expression in synovial sarcomas

Abstract 

Alterations to p53 seem to be of prognostic significance in soft tissue sarcomas, but their significance for synovial sarcomas has not been studied. We analysed 34 synovial sarcomas in 19 patients for p53 alterations (p53 gene mutations + p53 immunopositivity) and examined this factor for its prognostic value in a group of 15 primary tumours. DNA was prepared from paraffin-embedded tumour material by a modified proteinase K/phenol/chloroform extraction. p53 gene mutations of exons 5–8 were analysed by the PCR-SSCP-sequencing method. p53 protein expression was evaluated by immunohistochemistry using the murine monoclonal antibody DO1. We found two missense mutations (5.9%) and ten p53 immunopositive cases (29.4%). Both tumours with p53 mutations showed p53 protein expression. There was no significant correlation between p53 alteration and histological subtype, age, sex, or tumour size. The 5-year survival rate was 24.1%. Overall survival was significantly reduced in patients having synovial sarcomas with p53 alterations (P<0.001). In the multivariate Cox’s analysis, only p53 alterations (P=0.032) and tumour size (P=0.023) emerged as independent prognostic factors. We suggest that p53 alterations may be a useful prognostic indicator in synovial sarcomas, allowing rational clinical treatment and follow-up.