Can p53, Ki-67 and bcl-2 predict biochemical failure after radical prostatectomy?

Background And Objective: To analyze p53, Ki-67 and bcl-2 expressions immunohistochemically and their predictive role in biochemical recurrence after radical prostatectomy.

Materials And Methods: Seventy one patients who had undergone radical prostatectomy between 1992 and 2001 were randomly selected. Tissue microarrays were constructed from their radical prostatectomy specimens. They contained four cores from neoplastic and additional four cores from corresponding non-neoplastic regions. Gleason score ranged from 6-9, and pathological stage ranged from T2N0Mx to T3BN1. Staining for bcl-2 was scored visually taking percent negative, weak, moderate and strong positivity into consideration. Strong immunoreactivity was considered positive for p53. Ki-67 index was measured as the percentage of positive nuclei among tumor cells. Statistical analysis was performed to explore correlations between staining patterns and clinicopathological prognostic parameters.

Results: The follow-up period extended from 13 to 112 months with a mean 60 (48 ± 23, 2) months. Of all, 38.02% had no evidence of disease, 52.1% were alive with disease and 9.8% were died during follow-up. The expression of p53, Ki-67 and bcl-2 in tumors were 39%, 76% and 5% respectively. While the secretory layer showed negative or weak bcl-2 staining in most cases, expression in basal cells was often stronger. Statistical analysis revealed differences in staining between normal and carcinoma for all three markers. There was no correlation between staining patterns and time to biochemical relapse. On the other hand, cases with higher Gleason sum showed the tendency for over expression of p53, Ki-67 and bcl-2 although the differences were not statistically different. Multivariate analysis revealed CMS group and seminal vesicle invasion as the independent predictors of PSA failure (log rank P = 0.0039 and P = 0.001, respectively).

Conclusion: The proteins bcl-2, p53 and Ki-67 were expressed at a different rate in normal and neoplastic prostate tissue. Bcl-2 was mainly expressed by basal cells in normal glands. p53 and Ki-67 expression were increased in most prostate carcinomas. However, overall expression levels did not correlate with biochemical recurrence in this study.