Protein expression of MDM2 and its clinicopathological relationships in human hepatocellular carcinoma.
OBJECTIVE
The transcription of mdm2 gene is activated by p53 and this limits the growth-suppressing activity of p53 by direct binding. It has been reported that MDM2 protein is overexpressed in several types of cancers. However, there have been no immunohistochemical studies on MDM2 in human hepatocellular carcinoma (HCC).


METHODS
We immunohistochemically examined the expression of MDM2 and the relationships between its expression and histological grade, clinicopathological parameters, p53 expression and patient survival in 107 patients with HCC.


RESULTS
The frequency of MDM2 positivity in the nuclei of HCC cells was 28/107 (26%). There was no correlation between the MDM2 expression and HCC grade. However, positivity of MDM2 expression significantly correlated with small HCC size (p<0.05, chi2 test) and the absence of vascular invasion (p<0.01, chi2 test). No significant differences were noted between MDM2 expression and capsular invasion or satellite nodules. Expression of MDM2 showed a significantly positive correlation with expression of p53 (p<0.03, chi2 test). Patients with positive expression of MDM2 had poorer prognosis than patients with negative MDM2 expression. MDM2 expression was the most useful independent factor for overall survival (p=0.0001).


CONCLUSIONS
MDM2 was expressed in 26% of HCC, and its expression correlated positively with p53 mutations. MDM2 over-expression is a useful predictor of poor prognosis in patients with HCC following hepatic resection.
Endo
K
K
Second Department of Pathology, Tottori University, Faculty of Medicine, Japan.
Ueda
T
T
Ohta
T
T
Terada
T
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D051736:Proto-Oncogene Proteins c-mdm2; D015996:Survival Rate
D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2