ANALYSIS OF KI-RAS, P53, AND MDM2 GENES IN UTERINE LEIOMYOMAS AND LEIOMYOSARCOMAS

Uterine sarcomas are unusual neoplasms of the female genital tract who se molecular etiology is largely unknown. We examined 20 leiomyomas as well as 23 uterine leiomyosarcomas for the presence of mutations in t he Ki-ras and p53 genes, and overexpression of the MDM2 gene. Codons 1 2, 13, and 61 from the Ki-ras gene were characterized for the presence of mutations by restriction enzyme polymorphisms using mismatched pri mers and nucleic acid sequencing as appropriate, Activated Ki-ras gene s were identified in 3/20 leiomyomas and 0/23 leiomyosarcomas. The p53 gene was analyzed by SSCP, nucleic acid sequencing, and immunohistoch emical staining, None of 20 leiomyomas and 6/23 leiomyosarcomas exhibi ted p53 abnormalities. The SSCP/sequencing results did not consistentl y correlate with the IHC staining. MDM2 overexpression occurred in 0/2 0 leiomyomas and 3/23 sarcomas. Clinical correlation suggested that tu mors with p53 mutations have a higher histologic grade or stage at pre sentation, We conclude that leiomyomas and leiomyosarcomas have differ ent patterns of molecular alterations and are separate biologic entiti es. In addition, p53 and MDM2 overexpression may play a role in the de velopment of a subset of leiomyosarcomas. (C) 1997 Academic Press.