The expression of waf-1, p53 and bcl-2 in prostatic adenocarcinoma.

OBJECTIVE: To determine the associations between the expression of waf-1 (a cyclin-dependent kinase inhibitor regulated by p53), p53, bcl-2 and tumour progression in prostate cancer. PATIENTS AND METHODS: Samples of prostatic tissue were obtained by biopsy or at prostatectomy from 40 men (mean age 73 years, range 55-88) with histologically confirmed prostate cancer, examined using immunohistochemical staining for the three gene products, and the expression related to the stage, grade, disease progression and survival of the patients. RESULTS: Fifteen of 18 patients whose tumours were positive for waf-1, 10 of 12 positive for bcl-2 and 17 of 19 positive for p53 had disease progression. Fifteen of 19 patients positive for p53 had poorly differentiated tumours compared with 11 of 21 negative for p53 (P < 0.05). A significant number of patients positive for p53 progressed and had a shorter time to progression compared to those negative for p53 (P < 0.05). There was no correlation between either waf-1 and/or bcl-2 staining and clinical grade, stage or tumour progression. CONCLUSIONS: This study confirmed the association of p53 protein accumulation with aggressive behaviour in prostate cancer and identified waf-1 protein in prostatic tumours. There was no evidence that the upregulation of waf-1 was associated with a better outcome in patients with prostate cancer.

bcl-2 overexpression combined with p53 protein accumulation correlates with hormone-refractory prostate cancer.

Seventy-seven men with histologically proven and newly diagnosed prostate cancer we investigated for the presence of bcl-2 protein overexpression and p53 protein accumulation 1 immunohistochemistry. Forty-five men had evidence of locally advanced and metastatic disease and we treated by means of hormone manipulation. Twenty-eight patients either failed to respond to initial hormone manipulation or relapsed within 37 months from diagnosis (median 20 months). Of the 77 cancers, 37 (48% showed bcl-2 overexpression at diagnosis. Twenty-seven of those were treated with androgen ablation and 2 (74%) had hormone-refractory disease (P = 0.0128). Twenty-three of 77 men (29.8%) had nuclear staining for p53 protein. Twenty-one of those were treated with hormone manipulation and 14 (66.6%) showed hormone resistance (P = 0.0012). Seventeen patients had both bcl-2 overexpression and p53 protein accumulation, 16 of whom were hormonally treated, with 13 (81.2%) having hormone-refractory disease (P < 0.0001). These findings suggest that the combined detection of p53 protein accumulation and bcl-2 overexpression may be useful in predicting hormone resistance in prostate cancer. By deregulating programmed cell death, alteration in these genes may prevent patients from responding to androgen ablation, or allow them to escape hormonal control of the disease.