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 (chi 2 = 0.0386) could be established, namely the incidence of mdm-2 expression increased with an increase in stage. Using Westem 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.
Eid
H
H
Department of Cytopathology, National Institute of Oncology, Budapest, Hungary.
Institoris
E
E
Géczi
L
L
Bodrogi
I
I
Bak
M
M
D000293:Adolescent; D000328:Adult; D015153:Blotting, Western; D018236:Carcinoma, Embryonal / Q000378:metabolism; D002822:Choriocarcinoma / Q000378:metabolism; D018237:Germinoma / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009687:Nuclear Proteins; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D051736:Proto-Oncogene Proteins c-mdm2; D018239:Seminoma / Q000378:metabolism; D013724:Teratoma / Q000378:metabolism; D013736:Testicular Neoplasms / Q000378:metabolism*
D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2