mdm-2 Expression in human testicular germ-cell tumors and its clinical value

Background. In germ cell testicular tumors (GCTT) mdm-2 gene was analyzed for amplification and transcripts but not for protein. The purpose of this study is to determine whether mdm-2 protein level is aberrant in GCTT and if so, what is the relationship between mdm-2 overexpression and other disease parameters including histologic subtypes, p53 status, metastatic potential and clinical stage. Methods. 81 testicular germ-cell tumors were screened for their mdm-2 expression at the protein levels using immunohistochemistry (IHC) and Western blot (WB) analysis. Results. Of 81 GCTTs 45 (55.55 %) showed mdm-2 nuclear immunoreactivity, 34 (41,97%) of which were strongly positive. The incidence of mdm-2 immunostaining was significantly higher (P=0.0007) in non-seminomas (NSGCT) than in seminomas (SGCT). The frequency of positive tumor was higher in tumors from metastatic patients than in tumors from metastatic-free patients (P = 0.011). mdm-2 expression was detected significantly more frequently in tumors of advanced stages, i.e. IIB, IIC and III versus tumors of early stages (I and II/A) (P = 0.0098). A significant difference between the three stages of disease as to the expression of mdm-2 (X 2 = 0.0386) could be established, namely the incidence of mdm-2 expression increased with an increase in stage. Using Western blotting 22 (68.75 %) out of 32 tumors overexpressed the mdm-2 oncoprotein of 90 kd (p90). Conclusions. mdm-2 expression as detected by immunohistochemistry may provide a reliable prognostic tool to isolate subgroups of patients with more aggressive GCTT.