MDM2 mRNA expression is a favorable prognostic factor in non-small-cell lung cancer

MDM2 is one of the downstream target genes for transcriptional activation b y the product of the p53 tumor-suppressor gene. Transactivation of MDM2 gen e expression is represented by the presence of a functional p53 protein. We hypothesized that MDM2 mRNA expression may be a more suitable prognostic f actor than p53 or MDM2 protein expression and p53 gene mutations, In this s tudy, expression of MDM2 mRNA, p53 protein, and MDM2 protein and mutations of the p53 gene were assessed in 81 lung tumor tissue specimens using RT-PC R, immunohistochemistry, and direct sequencing among exons 5-8, respectivel y, By immunohistochemistry, 33 and 42 of 81 patients with p53 (40.7%) and M DM2 (51.5%) protein expression were found in lung tumor specimens, respecti vely. The p53 direct sequencing data indicated that 13 of 81 patients (16.0 %) had p53 mutations. However, Kaplan-Meier analysis showed that p53 protei n and MDM2 protein expression and p53 mutation were not useful as prognosti c factors. Interestingly, the survival of patients with MDM2 mRNA expressio n was longer than that of patients without MDM2 mRNA expression, though MDM 2 mRNA expression was not associated with clinicopathological parameters, i ncluding tumor grade, tumor stage, tumor type, and TNM values. Moreover, Co x regression analysis showed that MDM2 mRNA expression was a significantly independent favorable prognostic factor in non-small-cell lung cancer (NSCL C) patients. Thus, measuring MDM2 mRNA expression using RT-PCR may be a sim ple, useful approach for predicting the survival of NSCLC patients. (C) 200 0 Wiley-Liss, Inc.