p53 nuclear accumulation as an early indicator of lethal prostate cancer

Abstract

Background: After radical prostatectomy (RP) for prostate cancer (PC), p53 alterations predict biochemical relapse (BCR), however, recent evidence suggests that metastatic relapse (MR) not BCR is a surrogate for PC specific mortality (PCSM). This updated analysis of a previously published study investigated the association between p53 aberrations, MR and PCSM in men with localised PC. Methods: Two hundred and seventy-one men with localised PC treated with RP were included. RP specimens stained for p53 by immunohistochemistry were scored as (a) percentage of p53-positive tumour nuclei; and (b) clustering, where ≥12 p53-positive cells within a ×200 power field was deemed ‘cluster positive’. Associations between p53 status and clinical outcomes (BCR, MR and PCSM) were evaluated. Results: Increasing percentage of p53-positive nuclei was significantly associated with shorter time to BCR, MR and PCSM (All p ' 0.001). Half of the patients were p53 cluster positive. p53 cluster positivity was significantly associated with poorer outcomes at all clinical endpoints (BCR: HR 2.0, 95% CI 1.51–2.65, p ' 0.001; MR: HR 4.1, 95% CI 2.02–8.14, p ' 0.001; PCSM: HR 12.2, 95% CI 1.6–93; p = 0.016). These associations were independent of other established prognostic variables. Conclusions: p53 aberrations in radical prostatectomy tissue predict clinically relevant endpoints of MR and PCSM.