Overexpression of MDM2 and p53 protein is infrequently but significantly associated with progression of human prostatic adenocarcinoma

Abstract

In the present immunohistochemical study using anti-p53 (DO-7) and anti-MDM2 (IF2) antibodies, we determined the frequency of p53 and MDM2 protein expression in a series of 115 primary prostatic adenocarcinomas (stage A1 to D2) and evaluated the reliability of p53 and MDM2 immunoreactivity as an indicator for tumor progression. Overall, 13.9% (16/115) of surgically resected tumors were positive for anti-p53 antibody. A significantly higher association of immunoreactivity for p53 was detected in both high-grade (4/16, 25%; p<0.05) and advanced stage tumors (14/73, 19.1%; p<0.05) compared with that of other grade or stage. Positive staining for anti-MDM2 antibody was observed in only 4.3% (5/115) of the tumors examined. However, nuclear MDM2 protein overexpression, detected as focal and markedly heterogeneous staining, was sometimes observed especially in advanced stage tumors (4 stage C and 1 stage D tumors), and was significantly more common in locally advanced cancers (p<0.05) than in those of other stage. Only 2 cases (1.7%) exhibited positive staining with both p53 and MDM2 antibodies. These findings suggest that p53 and MDM2 alterations might play significant roles in the development and progression of some advanced stage or high-grade prostatic cancers, although MDM2 and p53 protein overexpression is infrequent in prostatic adenocarcinoma.