p53 expression and clinical outcome in prostate cancer

Abstract

Abnormally high levels of expression of p53 protein are found in many human cancers. In most cases increased expression is associated with point mutations in one allele of the p53 gene and loss of the other allele. Accumulation of the protein product can be detected by immunohistochemistry. p53 protein expression in 68 men with prostate cancer, followed up for at least 8 years or until death, was assessed by immunohistochemistry. The aim of the study was to determine the association between p53 protein expression, cell cycling and clinical outcome. Nine (13%) of 68 tumours stained positively for p53; all 9 tumours were category T3 or T4. p53 positive tumours had a significantly greater Gleason score than p53 negative tumours. Eight of the 9 p53 positive tumours had > 10% cells in G2 + mitosis, compared with 61% of p53 negative tumours. All 17 patients with p53 positive tumours available for follow-up progressed clinically, compared with 28 of 38 patients (74%) with p53 negative tumours. The median time to progression was 12 months in p53 positive tumours and 24 months in p53 negative tumours. Median survival in p53 positive tumours was 40 months, compared with 76 months in p53 negative tumours. This study demonstrates that overexpression of p53 in a small population of prostate cancers is associated with a poor prognosis in terms of progression and survival.