Apoptotic bodies and the expression of bcl-2 and p 53 in high-grade prostatic intraepithelial neoplasia and clinically localized prostate cancer
Johnson MI., Robinson MC., March C., Hamdy FC.
Introduction: Over-expression of bcl-2 and p53 is associated with a poor prognosis in prostate cancer. We compared the expression of bcl-2 and p53 with the apoptotic index (AI) in radical prostatectomies performed for clinically localized prostate cancer. Materials and methods: The AI was assessed on routine sections in areas of high-grade PIN (HGPIN), prostate cancer and BPH from 34 radical prostatectomies. Immunohistochemistry was performed on paraffin-embedded sections using monoclonal antibodies to DO-1, DO-7 and bcl-2. Results: The AI was significantly increased in prostate cancer (mean 0.25%, SD 0.14%) compared with HGPIN (mean O16%. SD 0.15%) and in HGPIN compared with BPH (P < 0.02). The AI also increased with increasing Gleason grade in prostate cancer and PIN. The AI was significantly increased in pathological stage T3 tumours (20 cases) compared with T2 tumours (14 cases; P < 0.01), and in HGPIN in T3 tumours, in HGPIN and prostate cancer in tumours with positive margins, but these differences were not significant. There was no correlation between the AI in either prostate cancer or HGPIN and pre-operative androgen blockade (eight of 34 patients). p53 was expressed in one of 29 (3.8%) of prostate cancers but was negative in all HGPIN. Bcl-2 expression was detected in 15 of 31 (48%) HGPIN samples compared with one of 29 (3.4%) prostate cancers (P < 0.001). Normal central zone glands and ejaculatory ducts were uniformly bcl-2-positive. Normal peripheral zone glands showed basal cell staining only for bcl-2. There was no correlation between bcl-2 expression and AI in HGPIN and no difference in p53 or bcl-2 expression in the group receiving pre-operative androgen blockade. Conclusion: The AI shows an increase from BPH through HGPIN to prostate cancer and is associated with increasing stage. p53 expression is uniformly low in early prostatic neoplasia. Bcl-2 over-expression appears to play a role in the development of HGPIN and the subsequent loss of bcl-2 expression may play a role in the progression from intraepithelial neoplasia to invasive prostate cancer. © 1997 British Journal of Urology.