Amplification of the mdm-2 gene and p53 abnormalities in uterine sarcomas.

The aim of this study is to address the role of mdm-2-gene amplification in the tumorigenesis of uterine sarcomas. Differential PCR with DNA from formalin-fixed paraffin-embedded specimens was employed in 12 patients with uterine sarcomas. We detected mdm-2-gene amplification in 4 out of 12 uterine sarcomas. The estimated copy number of the mdm-2 gene ranged from 4 to 13. Positive cases included 1 leiomyosarcoma and 3 carcinosarcomas, however, there was no correlation between mdm-2-gene amplification and clinicopathological characteristics. Over-expression of p53 protein was also immunohistochemically studied in the same series of patients: 4 out of 8 carcinosarcomas displayed p53 immunoreactivity. Taking these results together, only one carcinosarcoma was found to have both mdm-2-gene amplification and p53 over-expression. In contrast, half of the patients were found to have alterations either of mdm-2 or of p53. These findings support the notion that mdm-2-gene amplification might be an alternative mechanism for escaping from the regulatory pathway of p53 to suppress cell growth.