Molecular abnormalities of p53, MDM2, and H-ras in synovial sarcoma

Forty-nine cases of synovial sarcoma were evaluated for mutation of the p53 gene, amplification of the MDM2 gene and mutation of the H-ras gene, and f or the relation of these factors to overall survival and clinicopathologic parameters. All investigations were carried out on formalin-fixed paraffin- embedded materials. Furthermore, we evaluated the expression of p53 protein , MDM2, and p21(WAF1/CIP1) immunohistochemically in these cases, together w ith an assessment of proliferative activities using monoclonal antibody MIB -1, Nine of the 49 cases (18.4%) had p53 gene alteration detected by polyme rase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and direct sequencing. Eleven cases (24%) showed nuclear accumulation of p53 pr otein in more than 10% of the tumor cells. Among them, only three cases con tained gene mutations. There was no correlation between p53 nuclear accumul ation and p53 gene alteration. MDM2 gene amplification, as shown by differe ntial PCR, was observed in 19 out of 47 cases (40%). Nineteen out of 49 cas es (38.8%) showed immunoreactivity for MDM2, MDM2 gene amplification and th e expression of MDM2 protein showed a significant positive relationship (P = 0.0004). Moreover, MDM2 immunoreaction was significantly correlated with nuclear accumulation of p53 protein (P = 0.023). Positive immunoreaction fo r p21(WAF1/CIP1) was observed in 21 out of 48 cases (43.8%), p21(WAF1/CIP1) expression was correlated with p53 protein expression. H-ms gene mutations were seen in only three cases (6.1%). All mutations were in codon 12 tone GGC-to-AGC [Gly-to-Ser] mutation and two GGC-to-GAC [Gly-to-Ap] mutations). The gene alteration of p53, MDM2, and H-ras did not affect the patients' p rognosis. Although the cases with positive immunoreaction for p53 tended to have a worse prognosis, the difference was not statistically significant ( P = 0.13). No correlation was observed between MIB-1 LI and the immunohisto chemical expression of p53, MDM2 and p21(WAF1/CIP1),, the mutation status o f p53 and H-ras. On the other hand, high MIB-1 LI (more than 10) significan tly correlated with poor prognosis (P < 0.0001). Our results suggest that p 53 gene mutation does not appear to be a major prognostic factor and H-ras mutations are infrequent in synovial sarcoma.