mdm2 mRNA level is a prognostic factor in soft tissue sarcoma

Background: The oncogenic properties of murine double minute-2 (mdm2) prote in over-expression, which mostly results from the interaction with the tumo r suppressor p53, are well described and their negative impacts on the prog nosis of affected patients is well characterized. However, clinical relevan ce of mdm2 mRNA expression is poorly investigated. Materials and Methods: In this study, 65 soft tissue sarcoma (STS) samples were analyzed for mdm2 mRNA expression by a quantitative reverse transcript ion polymerase chain reaction (RT-PCR) approach using available validated r eady-to-use assays based on the TaqMan(R) technology (PE Applied Biosystems , Weiterstadt, Germany). Mdm2 data were correlated to glyceraldehyde-3-phos phate dehydrogenase (GAPDH) expression calculated from the same sample. Results: For patients with a mdm2/GAPDH mRNA ratio below 50 zmol/amol the s urvival was strikingly reduced in comparison to patients with a ratio of gr eater than or equal to 50 (p = 0.0241). Multivariate Cox analysis showed th at the difference in prognosis for patients with tumor stage 2 and 3 became even more pronounced between patients with a ratio of <50 zmol/amol and pa tients with a ratio of greater than or equal to 50 (p = 0.0041; RR = 5.6) T o test if the group with an mdm2 mRNA expression greater than or equal to 5 0 is homogenous concerning the prognosis, the group was divided into three subgroups with values of 50 to <100, 100 to <500 and greater than or equal to 500. The subgroup with values of 100 to <500 showed the best prognosis ( p = 0.0164); whereas, the one with values of 50 to <100 showed the worst pr ognosis in this group and, in between, was the one with values of greater t han or equal to 500. After omitting patients of stage 1 and 4, the subgroup with values of 100 to <500 showed an even more striking best prognosis (p = 0.0015); the other subgroups remained in the same sequence. The risk of t umor-related death over 5 years was most conspicuous in patients with mdm2 mRNA expression <50 than in those with ratios of 100 to <500 displaying a 1 3.3-fold higher risk. In a comparison between mdm2 mRNA levels and P53 prot ein expression or p53 mutational status, no relationship was found. Conclusions: In our study, the mdm2 mRNA level appears to be an independent prognostic factor for STS patients, marking its role in STS genesis and as a potential factor for gene therapeutical approaches.