The expression of the MDM2 gene, a p53 binding protein, in thyroid carcinogenesis.

Background. The authors previously found p53 mutations in 24% of malignant thyroid tumors, representing a wide staging spectrum. Overexpression of MDM2, most often due to gene amplification, has ben suggested to be ab additional mechanism for abrogation of the p53 function. In the current study. MDM2 gene expression and amplification were examined in a randomly selected subset of these tumors to explore the possibility that wildtype p53 may be inactivated by complexing with MDM2 in specimens without p53 mutations. Methods. MDM2 gene expression and amplification were studied by Northern and Southern blot analysis, respectively. Twenty-two thyroid tumors were included: 16 papillary carcinomas, 1 follicular carcinoma, 3 anaplastic carcinomas, and 2 multinodular goiters (adenomatousgoiters). Results. A two- to threefold increase in MDM2 expression in 4 of 20 thyroid carcinomas was found. It was noteworthy that all of these four samples harbored p53 mutations. The association between increased MDM2 expression and p53 mutation was statistically significant (P < 0.005). No evidence of MDM2 gene amplification or rearrangement accounting for such an increase in MDM2 expression was found. Conclusion. Genetic and/or environmental factors contributing to random p53 mutations also may cause increased MDM2 expression. Given the moderate increases in MDM2 expression without associated genetic alterations such as gene amplification and rearrangement, MDM2 may not play any significant role in the developmetn and progression of thyroid carcinoma. Cancer 1995; 76:314–8.