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.
Seki
A
A
Department of Obstetrics and Gynecology, Okayama University Medical School, Japan.
Kodama
J
J
Miyagi
Y
Y
Kamimura
S
S
Yoshinouchi
M
M
Kudo
T
T
D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009687:Nuclear Proteins; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051736:Proto-Oncogene Proteins c-mdm2; D012509:Sarcoma / Q000737:chemistry / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*; D014594:Uterine Neoplasms / Q000737:chemistry / Q000235:genetics*
D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2