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

Abstract

Seventy-seven men with histologically proven and newly diagnosed prostate cancer were investigated for the presence of bcl-2 protein overexpression and p53 protein accumulation by immunohistochemistry. Forty-five men had evidence of locally advanced and metastatic disease and were 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 20 (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,, alterations in these genes may prevent patients from responding to androgen ablation, or allow them to escape hormonal control of the disease.