THE EXPRESSION OF THE MDM2 GENE, A P53 BINDING-PROTEIN, IN THYROID CARCINOGENESIS

Background. The authors previously found p53 mutations in 24% of malig nant thyroid tumors, representing a wide staging spectrum. Overexpress ion of MDM2, most often due to gene amplification, hits been suggested to be an additional mechanism for abrogation of the p53 function. In the current study, MDM2 gene expression and amplification were examine d in a randomly selected subset of these tumors to explore the possibi lity that wild-type p53 may be inactivated by complexing with MDM2 in specimens without p53 mutations. Methods. MDM2 gene expression and amp lification were studied by Northern and Southern blot analysis, respec tively. Twenty-two thyroid tumors were included: 16 papillary carcinom as, 1 follicular carcinoma, 3 anaplastic carcinomas, and 2 multinodula r goiters (adenomatous goiters). Results. A two- to threefold increase in MDM2 expression in 4 of 20 thyroid carcinomas was found. It was no teworthy that all of these four samples harbored p53 mutations. The as sociation between increased MDM2 expression and p53 mutation was stati stically significant (P < 0.005). No evidence of MDM2 gene amplificati on or rearrangement accounting for such an increase in MDM2 expression was found. Conclusions. Genetic and/or environmental factors contribu ting to random p53 mutations also may cause increased MDM2 expression. Given the moderate increase in MDM2 expression without associated gen etic alterations such as gene amplification and rearrangement, MDM2 ma y not play any significant role in the development and progression of thyroid carcinoma.