Abnormal expression of MDM2 in prostate carcinoma.

Mutation of p53 is rare in localized prostate carcinoma. The oncoprotein MDM2, whose gene has a response element for p53, promotes the degradation of p53 protein and inhibits its transcriptional activation of genes related to cell cycle arrest and apoptosis, constituting a negative feedback control. We studied p53 and MDM2 expression by immunohistochemistry and looked for mutations in p53 exons 5 to 8 by polymerase chain reaction-single strand conformational polymorphism in 118 patients submitted to radical prostatectomy for localized prostate cancer. In 28 cases, we studied cell proliferation by immunohistochemistry, using antibody for Ki-67, and apoptosis by the deoxynucleotidyl transferase mediated dUTP biotin nick end labeling technique. Although no p53 mutations were found, p53 protein was detected in 31.4% of the cases, and these cases had higher Gleason scores (P = .03) and more advanced tumor stages (P = .02). MDM2 was overexpressed in 40.7% of the cases, and these cases had greater tumor volumes (P = .001). Tumors that were positive for both p53 and MDM2 were larger (P = .003) and of more advanced stage (P = .03). Within the 28-case subset, the proliferative index was higher among MDM2-positive tumors (P = .046), and the apoptotic index was lower among p53-positive tumors (P = .01). We conclude that, although p53 mutation is a rare event in prostate carcinogenesis, the detection of p53 protein by immunohistochemistry is common and is associated with decreased apoptosis and increased histologic grade and tumor stage. We also conclude that the overexpression of MDM2 has a role in prostate carcinogenesis, being frequently detected and associated with increased cell proliferation and tumor volume. Finally, we propose that the MDM2-positive/p53-positive phenotype identifies prostate cancers with aggressive behavior.

Urinary continence and pathological outcome after bladder neck preservation during radical retropubic prostatectomy: a randomized prospective trial.

PURPOSE: Bladder neck preservation during radical prostatectomy has been advocated for improving urinary continence. We compared bladder neck preservation and resection in a randomized trial, looking at continence rates and surgical cancer control. MATERIALS AND METHODS: Patients with stage T1c-T2c prostate cancer underwent radical retropubic prostatectomy with maximal preservation of the external urinary sphincter. Bladder neck preservation or resection was chosen by chance during surgery. Urinary continence (1 or no protective pad daily) was assessed by interview 2 days after catheter removal, and 2 and 6 months after surgery. The surgeon, pathologist and interviewer were the same throughout. Neither patient nor interviewer knew which procedure was done. Planned enrollment was 120. RESULTS: Enrollment was stopped after 70 patients because surgical margins were positive only at the bladder neck in 10% of the preservation group but in none of the resection group (p = 0.08). Each group was assigned 35 patients but the bladder neck could not be preserved in 4 and 1 died, leaving 31 in the preservation group and 38 in the resection group. There were no statistically significant differences between groups in early or late urinary continence rates. Two days after catheter removal, and 2 and 6 months after surgery the respective rates were 79%, 87% and 95% with resection, and 67%, 87% and 97% with preservation. CONCLUSIONS: In our opinion bladder neck preservation during radical retropubic prostatectomy does not improve urinary continence and might compromise cancer control. The external sphincter appears more important for continence after radical prostatectomy.