mdm2 gene amplification and overexpression in non-small cell lung carcinomas with accumulation of the p53 protein in the absence of p53 gene mutations

Fifty-three non-small cell lung carcinomas (NSCLC), previously investigated for p53 abnormalities, were studied to evaluate the status of the mdm2 gene by Southern and Northern blot analysis and expression of the mdm2 protein by immunohistochemistry with specific monoclonal antibodies. Amplification and overexpression of the mdm2 gene and nuclear accumulation of its protein product were observed in three (6%) of the NSCLC examined. All of the tumors having mdm2 abnormalities belonged to a subset of NSCLC characterized by a strong accumulation of the p53 protein in the absence of p53 gene mutations. Since mdm2 is capable of forming tight complexes with p53, possibly stabilizing it, our results suggest that this event may take place in a low percentage of NSCLC. Moreover, all of the mdm2-positive tumors were histologically classified as lung adenocarcinomas. This may indicate that the mdm2 gene is preferentially altered in this particular subtype of lung tumors.